Showing papers by "Primary Children's Hospital published in 2016"

Transcatheter or Surgical Aortic-Valve Replacement in Intermediate-Risk Patients.

Abstract: BackgroundPrevious trials have shown that among high-risk patients with aortic stenosis, survival rates are similar with transcatheter aortic-valve replacement (TAVR) and surgical aortic-valve replacement. We evaluated the two procedures in a randomized trial involving intermediate-risk patients. MethodsWe randomly assigned 2032 intermediate-risk patients with severe aortic stenosis, at 57 centers, to undergo either TAVR or surgical replacement. The primary end point was death from any cause or disabling stroke at 2 years. The primary hypothesis was that TAVR would not be inferior to surgical replacement. Before randomization, patients were entered into one of two cohorts on the basis of clinical and imaging findings; 76.3% of the patients were included in the transfemoral-access cohort and 23.7% in the transthoracic-access cohort. ResultsThe rate of death from any cause or disabling stroke was similar in the TAVR group and the surgery group (P=0.001 for noninferiority). At 2 years, the Kaplan–Meier event...

Cannabidiol in patients with treatment-resistant epilepsy: an open-label interventional trial

Abstract: Summary Background Almost a third of patients with epilepsy have a treatment-resistant form, which is associated with severe morbidity and increased mortality. Cannabis-based treatments for epilepsy have generated much interest, but scientific data are scarce. We aimed to establish whether addition of cannabidiol to existing anti-epileptic regimens would be safe, tolerated, and efficacious in children and young adults with treatment-resistant epilepsy. Methods In this open-label trial, patients (aged 1–30 years) with severe, intractable, childhood-onset, treatment-resistant epilepsy, who were receiving stable doses of antiepileptic drugs before study entry, were enrolled in an expanded-access programme at 11 epilepsy centres across the USA. Patients were given oral cannabidiol at 2–5 mg/kg per day, up-titrated until intolerance or to a maximum dose of 25 mg/kg or 50 mg/kg per day (dependent on study site). The primary objective was to establish the safety and tolerability of cannabidiol and the primary efficacy endpoint was median percentage change in the mean monthly frequency of motor seizures at 12 weeks. The efficacy analysis was by modified intention to treat. Comparisons of the percentage change in frequency of motor seizures were done with a Mann-Whitney U test. Results Between Jan 15, 2014, and Jan 15, 2015, 214 patients were enrolled; 162 (76%) patients who had at least 12 weeks of follow-up after the first dose of cannabidiol were included in the safety and tolerability analysis, and 137 (64%) patients were included in the efficacy analysis. In the safety group, 33 (20%) patients had Dravet syndrome and 31 (19%) patients had Lennox-Gastaut syndrome. The remaining patients had intractable epilepsies of different causes and type. Adverse events were reported in 128 (79%) of the 162 patients within the safety group. Adverse events reported in more than 10% of patients were somnolence (n=41 [25%]), decreased appetite (n=31 [19%]), diarrhoea (n=31 [19%]), fatigue (n=21 [13%]), and convulsion (n=18 [11%]). Five (3%) patients discontinued treatment because of an adverse event. Serious adverse events were reported in 48 (30%) patients, including one death—a sudden unexpected death in epilepsy regarded as unrelated to study drug. 20 (12%) patients had severe adverse events possibly related to cannabidiol use, the most common of which was status epilepticus (n=9 [6%]). The median monthly frequency of motor seizures was 30·0 (IQR 11·0–96·0) at baseline and 15·8 (5·6–57·6) over the 12 week treatment period. The median reduction in monthly motor seizures was 36·5% (IQR 0–64·7). Interpretation Our findings suggest that cannabidiol might reduce seizure frequency and might have an adequate safety profile in children and young adults with highly treatment-resistant epilepsy. Randomised controlled trials are warranted to characterise the safety profile and true efficacy of this compound. Funding GW Pharmaceuticals, Epilepsy Therapy Project of the Epilepsy Foundation, Finding A Cure for Epilepsy and Seizures.

Phase I/Phase II Study of Blinatumomab in Pediatric Patients With Relapsed/Refractory Acute Lymphoblastic Leukemia

Abstract: Purpose Blinatumomab is a bispecific T-cell engager antibody construct targeting CD19 on B-cell lymphoblasts. We evaluated the safety, pharmacokinetics, recommended dosage, and potential for efficacy of blinatumomab in children with relapsed/refractory B-cell precursor acute lymphoblastic leukemia (BCP-ALL). Methods This open-label study enrolled children < 18 years old with relapsed/refractory BCP-ALL in a phase I dosage-escalation part and a phase II part, using 6-week treatment cycles. Primary end points were maximum-tolerated dosage (phase I) and complete remission rate within the first two cycles (phase II). Results We treated 49 patients in phase I and 44 patients in phase II. Four patients had dose-limiting toxicities in cycle 1 (phase I). Three experienced grade 4 cytokine-release syndrome (one attributed to grade 5 cardiac failure); one had fatal respiratory failure. The maximum-tolerated dosage was 15 µg/m2/d. Blinatumomab pharmacokinetics was linear across dosage levels and consistent among age groups. On the basis of the phase I data, the recommended blinatumomab dosage for children with relapsed/refractory ALL was 5 µg/m2/d for the first 7 days, followed by 15 µg/m2/d thereafter. Among the 70 patients who received the recommended dosage, 27 (39%; 95% CI, 27% to 51%) achieved complete remission within the first two cycles, 14 (52%) of whom achieved complete minimal residual disease response. The most frequent grade ≥ 3 adverse events were anemia (36%), thrombocytopenia (21%), and hypokalemia (17%). Three patients (4%) and one patient (1%) had cytokine-release syndrome of grade 3 and 4, respectively. Two patients (3%) interrupted treatment after grade 2 seizures. Conclusion This trial, which to the best of our knowledge was the first such trial in pediatrics, demonstrated antileukemic activity of single-agent blinatumomab with complete minimal residual disease response in children with relapsed/refractory BCP-ALL. Blinatumomab may represent an important new treatment option in this setting, requiring further investigation in curative indications.

Multicenter Evaluation of BioFire FilmArray Meningitis/Encephalitis Panel for Detection of Bacteria, Viruses, and Yeast in Cerebrospinal Fluid Specimens

Abstract: Rapid diagnosis and treatment of infectious meningitis and encephalitis are critical to minimize morbidity and mortality. Comprehensive testing of cerebrospinal fluid (CSF) often includes Gram stain, culture, antigen detection, and molecular methods, paired with chemical and cellular analyses. These methods may lack sensitivity or specificity, can take several days, and require significant volume for complete analysis. The FilmArray Meningitis/Encephalitis (ME) Panel is a multiplexed in vitro diagnostic test for the simultaneous, rapid (∼1-h) detection of 14 pathogens directly from CSF specimens: Escherichia coli K1, Haemophilus influenzae, Listeria monocytogenes, Neisseria meningitidis, Streptococcus pneumoniae, Streptococcus agalactiae, cytomegalovirus, enterovirus, herpes simplex virus 1 and 2, human herpesvirus 6, human parechovirus, varicella-zoster virus, and Cryptococcus neoformans/Cryptococcus gattii We describe a multicenter evaluation of 1,560 prospectively collected CSF specimens with performance compared to culture (bacterial analytes) and PCR (all other analytes). The FilmArray ME Panel demonstrated a sensitivity or positive percentage of agreement of 100% for 9 of 14 analytes. Enterovirus and human herpesvirus type 6 had agreements of 95.7% and 85.7%, and L. monocytogenes and N. meningitidis were not observed in the study. For S. agalactiae, there was a single false-positive and false-negative result each, for a sensitivity and specificity of 0 and 99.9%, respectively. The specificity or negative percentage of agreement was 99.2% or greater for all other analytes. The FilmArray ME Panel is a sensitive and specific test to aid in diagnosis of ME. With use of this comprehensive and rapid test, improved patient outcomes and antimicrobial stewardship are anticipated.

Shared Genetic Predisposition in Peripartum and Dilated Cardiomyopathies

Abstract: Background Peripartum cardiomyopathy shares some clinical features with idiopathic dilated cardiomyopathy, a disorder caused by mutations in more than 40 genes, including TTN, which encodes the sarcomere protein titin. Methods In 172 women with peripartum cardiomyopathy, we sequenced 43 genes with variants that have been associated with dilated cardiomyopathy. We compared the prevalence of different variant types (nonsense, frameshift, and splicing) in these women with the prevalence of such variants in persons with dilated cardiomyopathy and with population controls. Results We identified 26 distinct, rare truncating variants in eight genes among women with peripartum cardiomyopathy. The prevalence of truncating variants (26 in 172 [15%]) was significantly higher than that in a reference population of 60,706 persons (4.7%, P=1.3×10(-7)) but was similar to that in a cohort of patients with dilated cardiomyopathy (55 of 332 patients [17%], P=0.81). Two thirds of identified truncating variants were in TTN, as seen in 10% of the patients and in 1.4% of the reference population (P=2.7×10(-10)); almost all TTN variants were located in the titin A-band. Seven of the TTN truncating variants were previously reported in patients with idiopathic dilated cardiomyopathy. In a clinically well-characterized cohort of 83 women with peripartum cardiomyopathy, the presence of TTN truncating variants was significantly correlated with a lower ejection fraction at 1-year follow-up (P=0.005). Conclusions The distribution of truncating variants in a large series of women with peripartum cardiomyopathy was remarkably similar to that found in patients with idiopathic dilated cardiomyopathy. TTN truncating variants were the most prevalent genetic predisposition in each disorder.

Risk factors for shunt malfunction in pediatric hydrocephalus: a multicenter prospective cohort study

Abstract: OBJECT The rate of CSF shunt failure remains unacceptably high. The Hydrocephalus Clinical Research Network (HCRN) conducted a comprehensive prospective observational study of hydrocephalus management, the aim of which was to isolate specific risk factors for shunt failure. METHODS The study followed all first-time shunt insertions in children younger than 19 years at 6 HCRN centers. The HCRN Investigator Committee selected, a priori, 21 variables to be examined, including clinical, radiographic, and shunt design variables. Shunt failure was defined as shunt revision, subsequent endoscopic third ventriculostomy, or shunt infection. Important a priori-defined risk factors as well as those significant in univariate analyses were then tested for independence using multivariate Cox proportional hazard modeling. RESULTS A total of 1036 children underwent initial CSF shunt placement between April 2008 and December 2011. Of these, 344 patients experienced shunt failure, including 265 malfunctions and 79 infections. The mean and median length of follow-up for the entire cohort was 400 days and 264 days, respectively. The Cox model found that age younger than 6 months at first shunt placement (HR 1.6 [95% CI 1.1-2.1]), a cardiac comorbidity (HR 1.4 [95% CI 1.0-2.1]), and endoscopic placement (HR 1.9 [95% CI 1.2-2.9]) were independently associated with reduced shunt survival. The following had no independent associations with shunt survival: etiology, payer, center, valve design, valve programmability, the use of ultrasound or stereotactic guidance, and surgeon experience and volume. CONCLUSIONS This is the largest prospective study reported on children with CSF shunts for hydrocephalus. It confirms that a young age and the use of the endoscope are risk factors for first shunt failure and that valve type has no impact. A new risk factor-an existing cardiac comorbidity-was also associated with shunt failure.

One-Year Clinical Outcomes With SAPIEN 3 Transcatheter Aortic Valve Replacement in High-Risk and Inoperable Patients With Severe Aortic Stenosis.

Abstract: Background:In the initial PARTNER trial (Placement of Aortic Transcatheter Valves) of transcatheter aortic valve replacement for high-risk (HR) and inoperable patients, mortality at 1 year was 24% ...

Outcome Measurement in ICU Survivorship Research From 1970 to 2013: A Scoping Review of 425 Publications.

Abstract: Objectives:To evaluate the study designs and measurement instruments used to assess physical, cognitive, mental health, and quality of life outcomes of survivors of critical illness over more than 40 years old as a first step toward developing a core outcome set of measures for future trials to impr

Psychiatric Symptoms in Acute Respiratory Distress Syndrome Survivors: A 1-Year National Multicenter Study.

Abstract: Objective:To evaluate prevalence, severity, and co-occurrence of and risk factors for depression, anxiety, and posttraumatic stress disorder symptoms over the first year after acute respiratory distress syndrome.Design:Prospective longitudinal cohort study.Settings:Forty-one Acute Respiratory Distre

Peer Support as a Novel Strategy to Mitigate Post-Intensive Care Syndrome.

Abstract: Post-intensive care syndrome, a condition defined by new or worsening impairment in cognition, mental health, and physical function after critical illness, has emerged in the past decade as a common and life-altering consequence of critical illness. New strategies are urgently needed to mitigate the risk of neuropsychological and functional impairment common after critical illness and to prepare and support survivors on their road toward recovery. The present state of critical care survivorship is described, and postdischarge care delivery in the United States and the potential impact of the present-day fragmented model of care delivery are detailed. A novel strategy that uses peer support groups could more effectively meet the needs of survivors of critical illness and mitigate post-intensive care syndrome.

Endoscopic third ventriculostomy in children: prospective, multicenter results from the Hydrocephalus Clinical Research Network

Abstract: OBJECTIVE Endoscopic third ventriculostomy (ETV) is now established as a viable treatment option for a subgroup of children with hydrocephalus. Here, the authors report prospective, multicenter results from the Hydrocephalus Clinical Research Network (HCRN) to provide the most accurate determination of morbidity, complication incidence, and efficacy of ETV in children and to determine if intraoperative predictors of ETV success add substantially to preoperative predictors. METHODS All children undergoing a first ETV (without choroid plexus cauterization) at 1 of 7 HCRN centers up to June 2013 were included in the study and followed up for a minimum of 18 months. Data, including detailed intraoperative data, were prospectively collected as part of the HCRN's Core Data Project and included details of patient characteristics, ETV failure (need for repeat hydrocephalus surgery), and, in a subset of patients, postoperative complications up to the time of discharge. RESULTS Three hundred thirty-six eligible children underwent initial ETV, 18.8% of whom had undergone shunt placement prior to the ETV. The median age at ETV was 6.9 years (IQR 1.7-12.6), with 15.2% of the study cohort younger than 12 months of age. The most common etiologies were aqueductal stenosis (24.8%) and midbrain or tectal lesions (21.2%). Visible forniceal injury (16.6%) was more common than previously reported, whereas severe bleeding (1.8%), thalamic contusion (1.8%), venous injury (1.5%), hypothalamic contusion (1.5%), and major arterial injury (0.3%) were rare. The most common postoperative complications were CSF leak (4.4%), hyponatremia (3.9%), and pseudomeningocele (3.9%). New neurological deficit occurred in 1.5% cases, with 0.5% being permanent. One hundred forty-one patients had documented failure of their ETV requiring repeat hydrocephalus surgery during follow-up, 117 of them during the first 6 months postprocedure. Kaplan-Meier rates of 30-day, 90-day, 6-month, 1-year, and 2-year failure-free survival were 73.7%, 66.7%, 64.8%, 61.7%, and 57.8%, respectively. According to multivariate modeling, the preoperative ETV Success Score (ETVSS) was associated with ETV success (p < 0.001), as was the intraoperative ability to visualize a "naked" basilar artery (p = 0.023). CONCLUSIONS The authors' documented experience represents the most detailed account of ETV results in North America and provides the most accurate picture to date of ETV success and complications, based on contemporaneously collected prospective data. Serious complications with ETV are low. In addition to the ETVSS, visualization of a naked basilar artery is predictive of ETV success.

Call to Action on Making Physical Activity Assessment and Prescription a Medical Standard of Care.

Abstract: The U.S. population is plagued by physical inactivity, lack of cardiorespiratory fitness, and sedentary lifestyles, all of which are strongly associated with the emerging epidemic of chronic disease. The time is right to incorporate physical activity assessment and promotion into health care in a manner that engages clinicians and patients. In April 2015, the American College of Sports Medicine and Kaiser Permanente convened a joint consensus meeting of subject matter experts from stakeholder organizations to discuss the development and implementation of a physical activity vital sign (PAVS) to be obtained and recorded at every medical visit for every patient. This statement represents a summary of the discussion, recommendations, and next steps developed during the consensus meeting. Foremost, it is a "call to action" for current and future clinicians and the health care community to implement a PAVS in daily practice with every patient.

Randomized placebo-controlled study of lovastatin in children with neurofibromatosis type 1

Abstract: Objective: To assess the efficacy of lovastatin on visuospatial learning and attention for treating cognitive and behavioral deficits in children with neurofibromatosis type 1 (NF1). Methods: A multicenter, international, randomized, double-blind, placebo-controlled trial was conducted between July 2009 and May 2014 as part of the NF Clinical Trials Consortium. Children with NF1 aged 8–15 years were screened for visuospatial learning or attention deficits (n = 272); 146 children demonstrated deficits at baseline and were randomly assigned to lovastatin (n = 74; 40 mg/d) or placebo (n = 70). Treatment was administered once daily for 16 weeks. Primary outcomes were total errors on the Cambridge Neuropsychological Test Automated Battery Paired Associate Learning task (visuospatial learning) and the Score subtest from the Test of Everyday Attention for Children (sustained attention). Secondary outcomes measured executive function, attention, visuospatial skills, behavior, and quality of life. Primary analyses were performed on the intention-to-treat population. Results: Lovastatin had no significant effect on primary outcomes after 16 weeks of treatment: visuospatial learning (Cohen d = −0.15, 95% confidence interval −0.47 to 0.18) or sustained attention (Cohen d = 0.19, 95% confidence interval −0.14 to 0.53). Lovastatin was well tolerated, with no increase in reported adverse events compared to placebo. Conclusions: Lovastatin administered once daily for 16 weeks did not improve visuospatial learning or attention in children with NF1 and is not recommended for amelioration of cognitive deficits in this population. ClinicalTrials.gov identifier: This study was registered at ClinicalTrials.gov (NCT00853580) and Australian New Zealand Clinical Trials Registry (ACTRN12607000560493). Classification of evidence: This study provides Class I evidence that for children with NF1, lovastatin does not improve visuospatial learning or attention deficits.

Development and Evaluation of the American College of Surgeons NSQIP Pediatric Surgical Risk Calculator.

Abstract: Background There is an increased desire among patients and families to be involved in the surgical decision-making process. A surgeon's ability to provide patients and families with patient-specific estimates of postoperative complications is critical for shared decision making and informed consent. Surgeons can also use patient-specific risk estimates to decide whether or not to operate and what options to offer patients. Our objective was to develop and evaluate a publicly available risk estimation tool that would cover many common pediatric surgical procedures across all specialties. Study Design American College of Surgeons NSQIP Pediatric standardized data from 67 hospitals were used to develop a risk estimation tool. Surgeons enter 18 preoperative variables (demographics, comorbidities, procedure) that are used in a logistic regression model to predict 9 postoperative outcomes. A surgeon adjustment score is also incorporated to adjust for any additional risk not accounted for in the 18 risk factors. Results A pediatric surgical risk calculator was developed based on 181,353 cases covering 382 CPT codes across all specialties. It had excellent discrimination for mortality (c-statistic = 0.98), morbidity (c-statistic = 0.81), and 7 additional complications (c-statistic > 0.77). The Hosmer-Lemeshow statistic and graphic representations also showed excellent calibration. Conclusions The ACS NSQIP Pediatric Surgical Risk Calculator was developed using standardized and audited multi-institutional data from the ACS NSQIP Pediatric, and it provides empirically derived, patient-specific postoperative risks. It can be used as a tool in the shared decision-making process by providing clinicians, families, and patients with useful information for many of the most common operations performed on pediatric patients in the US.

Right Ventricular Function in Peripartum Cardiomyopathy at Presentation Is Associated With Subsequent Left Ventricular Recovery and Clinical Outcomes

Abstract: Background— Peripartum cardiomyopathy has variable disease progression and left ventricular (LV) recovery We hypothesized that baseline right ventricular (RV) size and function are associated with LV recovery and outcome Methods and Results— Investigations of Pregnancy-Associated Cardiomyopathy was a prospective 30-center study of 100 peripartum cardiomyopathy women with LV ejection fraction (LVEF) <45% within 13 weeks after delivery Baseline RV function was assessed by echocardiographic end-diastolic area, end-systolic area, fractional area change, tricuspid annular plane excursion, and RV speckle-tracking longitudinal strain LV recovery was defined as LVEF of ≥50% at 1 year, persistent severe LV dysfunction as LVEF of ≤35%, and major events as death, transplant, or LV assist device implantation RV measurements were feasible for 90 of the 96 patients (94%) with echocardiograms available Mean baseline LVEF was 36±9% RV fractional area change was <35% in 38% of patients Of 84 patients with 1-year follow-up data, 63 (75%) had LV recovery and 11 (13%) had LVEF of ≤35% or a major event (4 LV assist devices and 2 deaths) Tricuspid annular plane excursion and RV strain did not predict outcome Baseline RV fractional area change by multivariable analysis was independently associated with subsequent LV recovery and clinical outcome Conclusions— Peripartum cardiomyopathy patients had a high incidence of LV recovery, but a significant minority had persistent LV dysfunction or a major clinical event by 1 year RV function per echocardiographic fractional area change at presentation was associated with subsequent LV recovery and clinical outcomes and thus is prognostically important

Distinct effects of obesity and puberty on risk and age at onset of pediatric MS

Abstract: Objective The aim of this study was to examine the relative contributions of body mass index (BMI) and pubertal measures for risk and age of onset of pediatric MS. Methods Case–control study of 254 (63% female) MS cases (onset<18 years of age) and 420 (49% female) controls conducted at 14 U.S. Pediatric MS Centers. Sex- and age-stratified BMI percentiles were calculated using CDC growth charts from height and weight measured at enrollment for controls, and within 1 year of onset for MS cases. Sex-stratified associations between MS risk and age at symptom onset with both BMI and pubertal factors were estimated controlling for race and ethnicity. Results Only 11% of girls and 15% of boys were prepubertal (Tanner stage I) at MS onset. 80% of girls had onset of MS after menarche. BMI percentiles were higher in MS cases versus controls (girls: P < 0.001; boys: P = 0.018). BMI was associated with odds of MS in multivariate models in postpubertal girls (OR = 1.60, 95% confidence interval [CI]: 1.12, 2.27, P = 0.009) and boys (OR = 1.43, 95% CI: 1.08, 1.88, P = 0.011). In girls with MS onset after menarche, higher BMI was associated with younger age at first symptoms (P = 0.031). Younger menarche was associated with stronger effects of BMI through mediation and interaction analysis. In pubertal/postpubertal boys, 89% of whom were obese/overweight, earlier sexual maturity was associated with earlier onset of MS (P < 0.001). Interpretation Higher BMI in early adolescence is a risk factor for MS in girls and boys. Earlier age at sexual maturity contributes to earlier age at MS onset, particularly in association with obesity.

A phase I study of intratumoral ipilimumab and interleukin-2 in patients with advanced melanoma

Abstract: // Abhijit Ray 1,* , Matthew A. Williams 2,* , Stephanie M. Meek 2 , Randy C. Bowen 3 , Kenneth F. Grossmann 1 , Robert H.I. Andtbacka 4 , Tawnya L. Bowles 5 , John R. Hyngstrom 4,5 , Sancy A. Leachman 6 , Douglas Grossman 1 , Glen M. Bowen 1 , Sheri L. Holmen 1 , Matthew W. VanBrocklin 1 , Gita Suneja 7 and Hung T. Khong 1 1 Division of Oncology, Huntsman Cancer Institute-University of Utah, Salt Lake City, UT, USA 2 Department of Pathology, University of Utah, Salt Lake City, UT, USA 3 School of Medicine, University of Utah, Salt Lake City, UT, USA 4 Section of Surgical Oncology, Division of General Surgery Huntsman Cancer Institute-University of Utah, Salt Lake City, UT, USA 5 Department of General Surgery, Intermountain Medical Center, Murray, UT, USA 6 Department of Dermatology, Oregon Health & Science University-Knight Cancer Institute, Portland, OR, USA 7 Department of Radiation Oncology, University of Utah, Salt Lake City, UT, USA * These authors have contributed equally to this work Correspondence to: Hung T. Khong, email: // Keywords : ipilimumab, interleukin-2, intratumoral, abscopal effect, immunotherapy Received : June 17, 2016 Accepted : June 25, 2016 Published : July 06, 2016 Abstract Purpose: Intratumoral interleukin-2 (IL-2) is effective but does not generate systemic immunity. Intravenous ipilimumab produces durable clinical response in a minority of patients, with potentially severe toxicities. Circulating anti-tumor T cells activated by ipilimumab may differ greatly from tumor-infiltrating lymphocytes activated by intratumoral ipilimumab in phenotypes and functionality. The objective of this study was to primarily assess the safety of intratumoral ipilimumab/IL-2 combination and to obtain data on clinical efficacy. Results: There was no dose limiting toxicity. While local response of injected lesions was observed in 67% patients (95% CI, 40%-93%), an abscopal response was seen in 89% (95% CI, 68%-100%). The overall response rate and clinical benefit rate by immune-related response criteria (irRC) was 40% (95% CI, 10%-70%) and 50% (95% CI, 19%-81%), respectively. Enhanced systemic immune response was observed in most patients and correlated with clinical responses. Experimental Design: Twelve patients with unresectable stages III/IV melanoma were enrolled. A standard 3+3 design was employed to assess highest tolerable intratumoral dose of ipilimumab and IL-2 based on toxicity during the first three weeks. Escalated doses of ipilimumab was injected into only one lesion weekly for eight weeks in cohorts of three patients. A fixed dose of IL-2 was injected three times a week into the same lesion for two weeks, followed by two times a week for six weeks. Conclusions: Intratumoral injection with the combination of ipilimumab/IL-2 is well tolerated and generates responses in both injected and non-injected lesions in the majority of patients.

Preclinical Assessment of a Fully Automated Multiplex PCR Panel for Detection of Central Nervous System Pathogens.

Abstract: We evaluated a multiplexed PCR panel for the detection of 16 bacterial, viral, and fungal pathogens in cerebrospinal fluid. Panel results were compared to routine testing, and discrepancies were resolved by additional nucleic acid amplification tests or sequencing. Overall, the positive and negative agreements across methods were 92.9% and 91.9%, respectively.

Treatment of Pediatric Septic Shock With the Surviving Sepsis Campaign Guidelines and PICU Patient Outcomes.

Abstract: Objectives:The Surviving Sepsis Campaign recommends rapid recognition and treatment of severe sepsis and septic shock. Few reports have evaluated the impact of these recommendations in pediatrics. We sought to determine if outcomes in patients who received initial care compliant with the Surviving S

Dexmedetomidine Use in Critically Ill Children With Acute Respiratory Failure.

Abstract: Objective:Care of critically ill children includes sedation but current therapies are suboptimal. To describe dexmedetomidine use in children supported on mechanical ventilation for acute respiratory failure.Design:Secondary analysis of data from the Randomized Evaluation of Sedation Titration for R

Perioperative Feeding Approaches in Single Ventricle Infants: A Survey of 46 Centers

Abstract: Background Feeding dysfunction occurs commonly in infants with single ventricle heart disease and impacts growth and long-term outcomes. Little evidence exists to guide safe feeding in this population. This study surveyed centers participating in the National Pediatric Cardiology Quality Improvement Collaborative to assess prevailing feeding practices amongthose caring for single ventricle neonates. Methods Web-based survey of 56 pediatric cardiac surgical centers was conducted. Questions addressed peri-operative feeding approaches and responses were presented and analyzed descriptively. Results Of 56 centers, 46 (82%) completed a survey. Preoperative feeding was common in single ventricle infants (30/46; 65%), routes varied. Centers who did not feed infants preoperatively cited the risk of necrotizing enterocolitis (16/16; 100%), presence of umbilical artery catheter (12/16; 75%), and prostaglandin infusion (9/16; 56%) as main concerns. 67% of centers reported no specific vital sign thresholds for withholding enteral feedings. In the postoperative period, most centers used an "internal guideline" (21/46; 46%) or an "informal practice" (15/46; 33%) to determine feeding readiness. Approaches to findings were significantly different among centers. About 40% of centers did not send patients home with feeding tubes, and there was no clear consensus between preferred feeding tube modality at discharge. Conclusion Considerable variation exists in feeding practices for infants with single ventricle congenital heart disease among 46 centers participating in a quality improvement collaborative. Although most centers generally feed infants preoperatively, feeding practices remain center-specific. Variability continues in the immediate post-operative and interstage periods. Further opportunities exist for investigation, standardization and development of best-practice feeding guidelines.

Validation of the Pittsburgh Infant Brain Injury Score for abusive head trauma

Abstract: BACKGROUND: Abusive head trauma is the leading cause of death from physical abuse. Misdiagnosis of abusive head trauma as well as other types of brain abnormalities in infants is common and contributes to increased morbidity and mortality. We previously derived the Pittsburgh Infant Brain Injury Score (PIBIS), a clinical prediction rule to assist physicians deciding which high-risk infants should undergo computed tomography of the head. METHODS: Well-appearing infants 30 to 364 days of age with temperature RESULTS: A total of 1040 infants were enrolled: 214 cases and 826 controls. The 5-point PIBIS included abnormality on dermatologic examination (2 points), age ≥3.0 months (1 point), head circumference >85th percentile (1 point), and serum hemoglobin CONCLUSIONS: Our data suggest that the PIBIS accurately identifies infants who would benefit from neuroimaging to evaluate for brain injury. An implementation analysis is needed before the PIBIS can be integrated into clinical practice.

Phase III randomized study of radiation and temozolomide versus radiation and nitrosourea therapy for anaplastic astrocytoma: results of NRG Oncology RTOG 9813.

Abstract: Background The primary objective of this study was to compare the overall survival (OS) of patients with anaplastic astrocytoma (AA) treated with radiotherapy (RT) and either temozolomide (TMZ) or a nitrosourea (NU). Secondary endpoints were time to tumor progression (TTP), toxicity, and the effect of IDH1 mutation status on clinical outcome. Methods Eligible patients with centrally reviewed, histologically confirmed, newly diagnosed AA were randomized to receive either RT+TMZ (n = 97) or RT+NU (n = 99). The study closed early because the target accrual rate was not met. Results Median follow-up time for patients still alive was 10.1 years (1.9-12.6 y); 66% of the patients died. Median survival time was 3.9 years in the RT/TMZ arm (95% CI, 3.0-7.0) and 3.8 years in the RT/NU arm (95% CI, 2.2-7.0), corresponding to a hazard ratio (HR) of 0.94 (P = .36; 95% CI, 0.67-1.32). The differences in progression-free survival (PFS) and TTP between the 2 arms were not statistically significant. Patients in the RT+NU arm experienced more grade ≥3 toxicity (75.8% vs 47.9%, P < .001), mainly related to myelosuppression. Of the 196 patients, 111 were tested for IDH1-R132H status (60 RT+TMZ and 51 RT+NU). Fifty-four patients were IDH negative and 49 were IDH positive with a better OS in IDH-positive patients (median survival time 7.9 vs 2.8 y; P = .004, HR = 0.50; 95% CI, 0.31-0.81). Conclusions RT+TMZ did not appear to significantly improve OS or TTP for AA compared with RT+ NU. RT+TMZ was better tolerated. IDH1-R132H mutation was associated with longer survival.

Intravenous Versus Oral Antibiotics for Postdischarge Treatment of Complicated Pneumonia

Abstract: BACKGROUND AND OBJECTIVES: Postdischarge treatment of complicated pneumonia includes antibiotics administered intravenously via a peripherally inserted central venous catheter (PICC) or orally. Antibiotics administered via PICC, although effective, may result in serious complications. We compared the effectiveness and treatment-related complications of postdischarge antibiotics delivered by these 2 routes. METHODS: This multicenter retrospective cohort study included children ≥2 months and RESULTS: Among 2123 children, 281 (13.2%) received antibiotics via PICC. Treatment failure rates were 3.2% among PICC and 2.6% among oral antibiotic recipients and were not significantly different between the groups in across-hospital-matched analysis (matched odds ratio [OR], 1.26; 95% confidence interval [CI], 0.54 to 2.94). PICC complications occurred in 7.1%. Adverse drug reactions occurred in 0.6% of children; PICC antibiotic recipients had greater odds of adverse drug reaction in across hospital matched analysis (matched OR, 19.1; 95% CI, 4.2 to 87.3). The high rate of PICC complications and differences in adverse drug reactions contributed to higher odds of the composite outcome of all related revisits among PICC antibiotic recipients (matched OR, 4.71; 95% CI, 2.97 to 7.46). CONCLUSIONS: Treatment failure rates between PICC and oral antibiotics did not differ. Children with complicated pneumonia should preferentially receive oral antibiotics at discharge when effective oral options are available.