MRI and the Critical Care Patient: Clinical, Operational, and Financial Challenges.

Neuroimaging in conjunction with a neurologic examination has become a valuable resource for today's intensive care unit (ICU) physicians. Imaging provides critical information during the assessment and ongoing neuromonitoring of patients for toxic-metabolic or structural injury of the brain. A patient's condition can change rapidly, and interventions may require imaging. When making this determination, the benefit must be weighed against possible risks associated with intrahospital transport. The patient's condition is assessed to decide if they are stable enough to leave the ICU for an extended period. Intrahospital transport risks include adverse events related to the physical nature of the transport, the change in the environment, or relocating equipment used to monitor the patient. Adverse events can be categorized as minor (e.g., clinical decompensation) or major (e.g., requiring immediate intervention) and may occur in preparation or during transport. Regardless of the type of event experienced, any intervention during transport impacts the patient and may lead to delayed treatment and disruption of critical care. This review summarizes the commentary on the current literature on the associated risks and provides insight into the costs as well as provider experiences. Approximately, one-third of patients who are transported from the ICU to an imaging suite may experience an adverse event. This creates an additional risk for extending a patient's stay in the ICU. The delay in obtaining imaging can negatively impact the patient's treatment plan and affect long-term outcomes as increased disability or mortality. Disruption of ICU therapy can decrease respiratory function after the patient returns from transport. Because of the complex care team needed for patient transport, the staff time alone can cost $200 or more. New technologies and advancements are needed to reduce patient risk and improve safety.

Understanding Treatment Response in Individual Profiles of Men with Prostatic Enlargement at Risk of Progression.

BACKGROUND: It is unclear how cumulative multivariable effects of clinically relevant covariates impact response to pharmacological treatments for lower urinary tract symptoms (LUTS)/benign prostatic enlargement (BPE). OBJECTIVE: To develop models to predict treatment response in terms of International Prostate Symptom Score (IPSS) and the risk of acute urinary retention (AUR) or BPE-related surgery, based on large data sets and using as predictors baseline characteristics that commonly define the risk of disease progression. DESIGN, SETTING, AND PARTICIPANTS: A total of 9167 patients with LUTS/BPE at risk of progression in three placebo-controlled dutasteride trials and one comparing dutasteride, tamsulosin, and dutasteride + tamsulosin combination therapy (CT) were included in the analysis to predict response to placebo up to 24 mo and active treatment up to 48 mo. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Predictors included age, IPSS, total prostate volume (PV), maximum urinary flow rate (Qmax), prostate-specific antigen, postvoid residual urine (PVR), α-blocker usage within 12 mo, and randomised treatment. A generalised least-squares model was developed for longitudinal IPSS and a Cox proportional-hazards model for time to first AUR/surgery. RESULTS AND LIMITATIONS: The vast majority of patients benefit from dutasteride or CT when compared with tamsulosin alone. The predicted IPSS improvement with dutasteride or CT increased with greater PV and severity of symptoms at baseline. The tamsulosin effect was lower with greater baseline PV and tended to decrease over time. Predicted AUR/surgery risk was greater with tamsulosin versus CT or dutasteride; this risk increased with larger PV, higher PVR, and lower Qmax (all at baseline). An educational interactive web-based tool facilitates visualisation of the results (www.bphtool.com). Limitations include: the placebo and active-treatment predictions are from different studies, the lack of similar studies for external validation, and the focus on a population at risk of progression from the 4-yr CombAT study. CONCLUSIONS: Predictive modelling based on large data sets and visualisation of the risk for individual profiles can improve our understanding of how risk factors for disease progression interact and affect response to different treatments, reinforcing the importance of an individualised approach for LUTS/BPE management. PATIENT SUMMARY: We used data from previous studies to develop statistical models for predicting how men with lower urinary tract symptoms or benign prostate enlargement and at risk of disease complications respond to certain treatments according to their individual characteristics.

Outcomes following formation of a dedicated pediatric liver transplant anesthesia team.

BACKGROUND: Given the complex nature of liver transplant surgery, adult centers typically use a dedicated liver transplant anesthesia team, which has improved patient outcomes. AIMS: Our goal was to determine whether a dedicated pediatric liver transplant anesthesia team was associated with improved patient outcomes. METHODS: This retrospective cohort study analyzed patients who underwent liver transplantation from April 2013 to September 2020 at St. Louis Children's Hospital. The general group (April 2013-December 2016) was compared with the liver group (January 2017-September 2020). Outcomes measured included cases per anesthesiologist, early extubation, ventilator days, fluid and blood administration, postoperative events, and intensive care unit and hospital length of stay (LOS). RESULTS: Patients in both groups had similar demographics. The average number of cases/anesthesiologist/year was 2.9 times higher in the liver group (mean (SD) general 0.7 (0.5), liver 2.0 (0.6), and difference in mean [95% CI] 1.3 [0.8, 1.8]). The rate of extubation in the operating room was higher for patients in the liver group (general 56%, liver 80%, and difference in proportion [95% CI] 24.7 [7.0, 42.4]), while the number of ventilator days was lower (mean (SD) general 2.1 (4.4), liver 1.1 (3.6), and difference in proportion [95%CI] -0.9 [-2.6, 0.7]). Colloid administration was higher in the liver group (mean (SD) general 23.9 (14.5) ml/kg, liver 48.4 (37.7) ml/kg, and difference in mean [95% CI] 24.6 [12.7, 36.4]), while fresh frozen plasma administration was lower in the liver group (mean (SD) general 15.3 (23.9) ml/kg, liver 6.2 (14) ml/kg, and difference in mean [95% CI] -9.0 [-16.8, -1.3]). There were no significant differences between the groups in postoperative events including blood product transfusions, vasopressor use, and thromboses, or in the intensive care unit and hospital LOS. CONCLUSIONS: The liver group was associated with increased early extubations, decreased ventilator days, and decreased fresh frozen plasma use.

Pharmacodynamic evaluation and safety assessment of treatment with antibodies to serum amyloid P component in patients with cardiac amyloidosis: an open-label Phase 2 study and an adjunctive immuno-PET imaging study.

BACKGROUND: In a Phase I study treatment with the serum amyloid P component (SAP) depleter miridesap followed by monoclonal antibody to SAP (dezamizumab) showed removal of amyloid from liver, spleen and kidney in patients with systemic amyloidosis. We report results from a Phase 2 study and concurrent immuno-positron emission tomography (PET) study assessing efficacy, pharmacodynamics, pharmacokinetics, safety and cardiac uptake (of dezamizumab) following the same intervention in patients with cardiac amyloidosis. METHODS: Both were uncontrolled open-label studies. After SAP depletion with miridesap, patients received ≤ 6 monthly doses of dezamizumab in the Phase 2 trial (n = 7), ≤ 2 doses of non-radiolabelled dezamizumab plus [89Zr]Zr-dezamizumab (total mass dose of 80 mg at session 1 and 500 mg at session 2) in the immuno-PET study (n = 2). Primary endpoints of the Phase 2 study were changed from baseline to follow-up (at 8 weeks) in left ventricular mass (LVM) by cardiac magnetic resonance imaging and safety. Primary endpoint of the immuno-PET study was [89Zr]Zr-dezamizumab cardiac uptake assessed via PET. RESULTS: Dezamizumab produced no appreciable or consistent reduction in LVM nor improvement in cardiac function in the Phase 2 study. In the immuno-PET study, measurable cardiac uptake of [89Zr]Zr-dezamizumab, although seen in both patients, was moderate to low. Uptake was notably lower in the patient with higher LVM. Treatment-associated rash with cutaneous small-vessel vasculitis was observed in both studies. Abdominal large-vessel vasculitis after initial dezamizumab dosing (300 mg) occurred in the first patient with immunoglobulin light chain amyloidosis enrolled in the Phase 2 study. Symptom resolution was nearly complete within 24 h of intravenous methylprednisolone and dezamizumab discontinuation; abdominal computed tomography imaging showed vasculitis resolution by 8 weeks. CONCLUSIONS: Unlike previous observations of visceral amyloid reduction, there was no appreciable evidence of amyloid removal in patients with cardiac amyloidosis in this Phase 2 trial, potentially related to limited cardiac uptake of dezamizumab as demonstrated in the immuno-PET study. The benefit-risk assessment for dezamizumab in cardiac amyloidosis was considered unfavourable after the incidence of large-vessel vasculitis and development for this indication was terminated. Trial registration NCT03044353 (2 February 2017) and NCT03417830 (25 January 2018).

Clinical moderators and predictors of cognitive-behavioral therapy by guided-self-help versus therapist-led for binge-eating disorder: Analysis of aggregated clinical trials.

OBJECTIVE: Cognitive-behavioral therapy (CBT)-therapist-led (CBTth) and guided-self-help (CBTgsh)-has efficacy for binge-eating disorder (BED) but many patients do not benefit sufficiently. We examined predictors and moderators for these two CBT methods. METHOD: Data were aggregated from randomized controlled trials (RCTs) testing psychosocial treatments for BED in the U.S. Predictors and moderators of outcomes (treatment completion and binge-eating remission) were examined in N = 457 participants who received either CBTgsh (N = 164) or CBTth (N = 293). RESULTS: Analyses, adjusting for demographic/clinical variables, indicated CBTth was significantly superior to CBTgsh for treatment completion (odds ratio [OR] = 20.0) and remission (OR = 14.6). For remission, analyses revealed significant predictors (age, treatment length, Weight Concern), a moderator (weight concern [OR = 5.13]), and a significant interaction between CBT-type and treatment length (OR = 2.66). For CBTgsh, longer treatment was associated with less remission, whereas for CBTth, longer treatment was associated with greater remission. For CBTgsh, 44.1% with low weight concern versus 56.3% with high weight concern achieved remission whereas for CBTth, 43.5% with high weight concern and 61.0% with low weight concern achieved remission. DISCUSSION: Analyses of aggregated RCT BED data, adjusting for demographic/clinical characteristics, indicated superiority (large effect-sizes) in treatment outcomes of CBTth over CBTgsh and that Weight Concern moderated outcomes.

Identification, preclinical profile, and clinical proof of concept of an orally bioavailable pro-drug of miridesap.

BACKGROUND AND PURPOSE: Miridesap, a depleter of serum amyloid P component (SAP), forms an essential component of a novel approach to remove systemic amyloid deposits; low oral bioavailability necessitates that it is given parenterally. We sought to identify and clinically characterise a pro-drug that preserves the pharmacological properties of miridesap while having adequate oral bioavailability and physical stability. EXPERIMENTAL APPROACH: We utilised a preclinical screening cascade focused on appropriate physicochemical properties, physical and gut stability, and conversion to miridesap in liver microsomes and blood. GSK3039294 (GSK294) had the desired in vitro profile and progressed to preclinical in vivo pharmacokinetic and safety assessments. Based on a favourable profile, it was tested in healthy participants after single and repeat dosing. KEY RESULTS: GSK294 was highly soluble and stable in simulated gastric and intestinal fluids, stable in intestinal microsomes, and permeable in Madine Darby Canine Kidney type II cells. GSK294 was rapidly hydrolysed to miridesap and its mono pro-drug ester in blood and liver microsomes. GSK294 showed good oral bioavailability of miridesap in rats and dogs. Following administration of GSK294 600 mg QD for 7 days in humans, pharmacodynamically active concentrations of miridesap were achieved with substantial and sustained depletion of plasma SAP. The study was terminated due to observations of arrhythmia, the relation of which to GSK294 remains unclear. CONCLUSION AND IMPLICATIONS: Using a preclinical screening cascade, we identified a pro-drug for a palindromic molecule with unique pharmacology (miridesap). The pro-drug depleted circulating SAP with a time course and extent similar to that of parenterally administered miridesap.

Practical experiences of adopting assurance as a quantitative framework to support decision making in drug development.

All clinical trials are designed for success of their primary objectives. Hence, evaluating the probability of success (PoS) should be a key focus at the design stage both to support funding approval from sponsor governance boards and to inform trial design itself. Use of assurance-that is, expected success probability averaged over a prior probability distribution for the treatment effect-to quantify PoS of a planned study has grown across the industry in recent years, and has now become routine within the authors' company. In this paper, we illustrate some of the benefits of systematically adopting assurance as a quantitative framework to support decision making in drug development through several case-studies where evaluation of assurance has proved impactful in terms of trial design and in supporting governance-board reviews of project proposals. In addition, we describe specific features of how the assurance framework has been implemented within our company, highlighting the critical role that prior elicitation plays in this process, and illustrating how the overall assurance calculation may be decomposed into a sequence of conditional PoS estimates which can provide greater insight into how and when different development options are able to discharge risk.

Extracellular volume with bolus-only technique in amyloidosis patients: Diagnostic accuracy, correlation with other clinical cardiac measures, and ability to track changes in amyloid load over time.

BACKGROUND: Extracellular volume (ECV) by T1 mapping requires the contrast agent distribution to be at equilibrium. This can be achieved either definitively with a primed contrast infusion (infusion ECV), or sufficiently with a delay postbolus (bolus-only ECV). For large ECV, the bolus-only approach measures higher than the infusion ECV, causing some uncertainty in diseases such as amyloidosis. PURPOSE: To characterize the relationship between the bolus-only and current gold-standard infusion ECV in patients with amyloidosis. STUDY TYPE: Bolus-only and infusion ECV were prospectively measured. POPULATION: In all, 186 subjects with systemic amyloidosis attending our clinic and 23 subjects with systemic amyloidosis who were participating in an open-label, two-part, dose-escalation, phase 1 trial. FIELD STRENGTH: Avanto 1.5T, Siemens Medical Solutions, Erlangen, Germany. ASSESSMENT: Bolus-only and infusion ECV were measured in all subjects using shortened modified Look-Locker inversion recovery (ShMOLLI) T1 mapping sequence. STATISTICAL TESTS: Pearson correlation coefficient (r); Bland-Altman; receiver operating characteristic (ROC) curve analysis. Linear regression model with a fractional polynomial transformation. RESULTS: The difference between the bolus-only and infusion myocardial ECV increased as the average of the two measures increased, with the bolus-ECV measuring higher. For an average ECV of 0.4, the difference was 0.013. The 95% limits of agreement for the two methods, after adjustment for the bias, were ±0.056. However, cardiac diagnostic accuracy was comparable (bolus-only vs. infusion ECV area under the curve [AUC] = 0.839 vs. 0.836), as were correlations with other clinical cardiac measures, and, in the trial patients, the ability to track changes in the liver/spleen with therapy. DATA CONCLUSION: In amyloidosis, with large ECVs, the bolus-only technique reads higher than the infusion technique, but clinical performance by any measure is the same. Given the work-flow advantages, these data suggest that the bolus-only approach might be acceptable for amyloidosis, and might support its use as a surrogate endpoint in future clinical trials. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 4 J. Magn. Reson. Imaging 2018;47:1677-1684.

Endoscopic Versus Open Repair for Craniosynostosis in Infants Using Propensity Score Matching to Compare Outcomes: A Multicenter Study from the Pediatric Craniofacial Collaborative Group.

BACKGROUND: The North American Pediatric Craniofacial Collaborative Group (PCCG) established the Pediatric Craniofacial Surgery Perioperative Registry to evaluate outcomes in infants and children undergoing craniosynostosis repair. The goal of this multicenter study was to utilize this registry to assess differences in blood utilization, intensive care unit (ICU) utilization, duration of hospitalization, and perioperative complications between endoscopic-assisted (ESC) and open repair in infants with craniosynostosis. We hypothesized that advantages of ESC from single-center studies would be validated based on combined data from a large multicenter registry. METHODS: Thirty-one institutions contributed data from June 2012 to September 2015. We analyzed 1382 infants younger than 12 months undergoing open (anterior and/or posterior cranial vault reconstruction, modified-Pi procedure, or strip craniectomy) or endoscopic craniectomy. The primary outcomes included transfusion data, ICU utilization, hospital length of stay, and perioperative complications; secondary outcomes included anesthesia and surgical duration. Comparison of unmatched groups (ESC: N = 311, open repair: N = 1071) and propensity score 2:1 matched groups (ESC: N = 311, open repair: N = 622) were performed by conditional logistic regression analysis. RESULTS: Imbalances in baseline age and weight are inherent due to surgical selection criteria for ESC. Quality of propensity score matching in balancing age and weight between ESC and open groups was assessed by quintiles of the propensity scores. Analysis of matched groups confirmed significantly reduced utilization of blood (26% vs 81%, P < .001) and coagulation (3% vs 16%, P < .001) products in the ESC group compared to the open group. Median blood donor exposure (0 vs 1), anesthesia (168 vs 248 minutes) and surgical duration (70 vs 130 minutes), days in ICU (0 vs 2), and hospital length of stay (2 vs 4) were all significantly lower in the ESC group (all P < .001). Median volume of red blood cell administered was significantly lower in ESC (19.6 vs 26.9 mL/kg, P = .035), with a difference of approximately 7 mL/kg less for the ESC (95% confidence interval for the difference, 3-12 mL/kg), whereas the median volume of coagulation products was not significantly different between the 2 groups (21.2 vs 24.6 mL/kg, P = .73). Incidence of complications including hypotension requiring treatment with vasoactive agents (3% vs 4%), venous air embolism (1%), and hypothermia, defined as <35°C (22% vs 26%), was similar between the 2 groups, whereas postoperative intubation was significantly higher in the open group (2% vs 10%, P < .001). CONCLUSIONS: This multicenter study of ESC versus open craniosynostosis repair represents the largest comparison to date. It demonstrates striking advantages of ESC for young infants that may result in improved clinical outcomes, as well as increased safety.

Preoperative malnutrition is associated with increased mortality and adverse outcomes after paediatric cardiac surgery.

BACKGROUND: Malnutrition is common in children with CHD and is likely to place them at an increased risk for adverse surgical outcomes. We sought to evaluate the impact of preoperative malnutrition on outcomes after paediatric cardiac surgery. METHODS: We conducted a retrospective analysis of patients from age 0 to 5 years undergoing cardiac surgery at Seattle Children's Hospital from 2006 to 2015. We used regression modelling to examine the impact of malnutrition on surgical outcomes. RESULTS: We found a non-linear relationship between low height-for-age and weight-for-age z-scores and mortality after surgery. In the range of z-score ⩽-2, each additional unit decrease in height-for-age or weight-for-age z-score was associated with a 2.9 or 2.1% increased risk for mortality, respectively. Each unit decrease in height-for-age z-score was associated with a 1.2% increased risk for cardiac arrest, 1.1% increased risk for infection, and an average of 1.7 additional hours of mechanical ventilation, 6 hours longer ICU stay, and 13 hours longer hospital stay. Each unit decrease in weight-for-age z-score was associated with a 0.7% increased risk for cardiac arrest, 0.8% increased risk for infection, and an average of 1.9 additional hours of mechanical ventilation and 5.3 additional hours of ICU stay. CONCLUSIONS: This study is unique in demonstrating a significant association between malnutrition and 30-day mortality and other adverse outcomes after paediatric cardiac surgery in a mixed population of CHD patients. By evaluating nutritional status as a continuous variable, we were able to clearly distinguish the point at which malnutrition begins to affect mortality.

Fruit Juice and Change in BMI: A Meta-analysis.

CONTEXT: Whether 100% fruit juice consumption causes weight gain in children remains controversial. OBJECTIVE: To determine the association between 100% fruit juice consumption and change in BMI or BMI z score in children. DATA SOURCES: PubMed, Embase, CINAHL, and Cochrane databases. STUDY SELECTION: Longitudinal studies examining the association of 100% fruit juice and change in BMI measures were included. DATA EXTRACTION: Two independent reviewers extracted data using a predesigned data collection form. RESULTS: Of the 4657 articles screened, 8 prospective cohort studies (n = 34 470 individual children) met the inclusion criteria. Controlling for total energy intake, 1 daily 6- to 8-oz serving increment of 100% fruit juice was associated with a 0.003 (95% CI: 0.001 to 0.004) unit increase in BMI z score over 1 year in children of all ages (0% increase in BMI percentile). In children ages 1 to 6 years, 1 serving increment was associated with a 0.087 (95% confidence interval: 0.008 to 0.167) unit increase in BMI z score (4% increase in BMI percentile). 100% fruit juice consumption was not associated with BMI z score increase in children ages 7 to 18 years. LIMITATIONS: All observational studies; studies differed in exposure assessment and covariate adjustment. CONCLUSIONS: Consumption of 100% fruit juice is associated with a small amount of weight gain in children ages 1 to 6 years that is not clinically significant, and is not associated with weight gain in children ages 7 to 18 years. More studies are needed in children ages 1 to 6 years.

Effect of ileal bile acid transporter inhibitor GSK2330672 on pruritus in primary biliary cholangitis: a double-blind, randomised, placebo-controlled, crossover, phase 2a study.

BACKGROUND: Up to 70% of patients with primary biliary cholangitis develop pruritus (itch) during the course of their disease. Treatment of pruritus in primary biliary cholangitis is challenging and novel therapies are needed. Ursodeoxycholic acid, the standard first-line treatment for primary biliary cholangitis, is largely ineffective for pruritus. We investigated the efficacy and safety of GSK2330672, a selective inhibitor of human ileal bile acid transporter (IBAT), in patients with primary biliary cholangitis with pruritus. METHODS: We conducted this phase 2a, double-blind, randomised, placebo-controlled, crossover trial in two UK medical centres. Following 2 weeks of open placebo run-in, patients were randomly assigned in a 1:1 ratio with a block size of 4 to receive GSK2330672 or placebo twice daily during two consecutive 14-day treatment periods in a crossover sequence. The treatment periods were followed by a 14-day single-blinded placebo follow-up period. The primary endpoints were safety of GSK2330672, assessed using clinical and laboratory parameters, and tolerability as rated by the Gastrointestinal Symptom Rating Scale. The secondary endpoints were changes in pruritus scores measured using the 0 to 10 numerical rating scale (NRS), primary biliary cholangitis-40 (PBC-40) itch domain score and 5-D itch scale, changes in serum total bile acids and 7 alpha hydroxy-4-cholesten-3-one (C4), and changes in the pharmacokinetic parameters of ursodeoxycholic acid and its conjugates. The trial was registered with ClinicalTrials.gov, number NCT01899703. FINDINGS: Between March 10, 2014, and Oct 7, 2015, we enrolled 22 patients. 11 patients were assigned to receive intervention followed by placebo (sequence 1), and 11 patients were assigned to receive placebo followed by intervention (sequence 2). One patient assigned to sequence 2 withdrew consent prior to receiving randomised therapy. One patient did not attend the placebo follow-up period, but was included in the final analysis. GSK2330672 treatment for 14 days was safe with no serious adverse events reported. Diarrhoea was the most frequent adverse event during treatment with GSK2330672 (seven with GSK2330672 vs one with placebo) and headache was the most frequent adverse event during treatment with placebo (seven with placebo vs six with GSK2330672). After GSK2330672 treatment, the percentage changes from baseline itch scores were -57% (95% CI -73 to -42, p<0·0001) in the NRS, -31% (-42 to -20, p<0·0001) in the PBC-40 itch domain and -35% (-45 to -25, p<0·0001) in the 5-D itch scale. GSK2330672 produced significantly greater reduction from baseline than the double-blind placebo in the NRS (-23%, 95% CI -45 to -1; p=0·037), PBC-40 itch domain, (-14%, -26 to -1; p=0·034), and 5-D itch scale (-20%, -34 to -7; p=0·0045). After GSK2330672 treatment, serum total bile acid concentrations declined by 50% (95% CI -37 to -61, p<0·0001) from 30 to 15 µM, with a significant 3·1-times increase (95% CI 2·4 to 4·0, p<0·0001) in serum C4 concentrations from 7·9 to 24·7ng/mL. INTERPRETATION: In patients with primary biliary cholangitis with pruritus, 14 days of ileal bile acid transporter inhibition by GSK2330672 was generally well tolerated without serious adverse events, and demonstrated efficacy in reducing pruritus severity. GSK2330672 has the potential to be a significant and novel advance for the treatment of pruritus in primary biliary cholangitis. Diarrhoea, the most common adverse event associated with GSK2330672 treatment, might limit the long-term use of this drug. FUNDING: GlaxoSmithKline and National Institute for Health Research.

Perioperative Outcomes and Management in Pediatric Complex Cranial Vault Reconstruction: A Multicenter Study from the Pediatric Craniofacial Collaborative Group.

BACKGROUND: The Pediatric Craniofacial Collaborative Group established the Pediatric Craniofacial Surgery Perioperative Registry to elucidate practices and outcomes in children with craniosynostosis undergoing complex cranial vault reconstruction and inform quality improvement efforts. The aim of this study is to determine perioperative management, outcomes, and complications in children undergoing complex cranial vault reconstruction across North America and to delineate salient features of current practices. METHODS: Thirty-one institutions contributed data from June 2012 to September 2015. Data extracted included demographics, perioperative management, length of stay, laboratory results, and blood management techniques employed. Complications and outlier events were described. Outcomes analyzed included total blood donor exposures, intraoperative and perioperative transfusion volumes, and length of stay outcomes. RESULTS: One thousand two hundred twenty-three cases were analyzed: 935 children aged less than or equal to 24 months and 288 children aged more than 24 months. Ninety-five percent of children aged less than or equal to 24 months and 79% of children aged more than 24 months received at least one transfusion. There were no deaths. Notable complications included cardiac arrest, postoperative seizures, unplanned postoperative mechanical ventilation, large-volume transfusion, and unplanned second surgeries. Utilization of blood conservation techniques was highly variable. CONCLUSIONS: The authors present a comprehensive description of perioperative management, outcomes, and complications from a large group of North American children undergoing complex cranial vault reconstruction. Transfusion remains the rule for the vast majority of patients. The occurrence of numerous significant complications together with large variability in perioperative management and outcomes suggest targets for improvement.

Making the Case for Palliative Care at the System Level: Outcomes Data.

BACKGROUND: A recent trend in health care is to integrate palliative care (PC) programs across multiple hospitals to reduce variation, improve quality, and reduce cost. OBJECTIVE: The study objective was to demonstrate the benefits of PC for a system. METHODS: The study was a descriptive study using retrospective medical records in seven federated hospitals where PC developed differently before system integration. Measured were length of stay (LOS), mortality, readmissions, saved intensive care unit (ICU) days, cost avoidance, and hospice referrals. RESULTS: PC services within the first 48 hours of admission demonstrate a shorter LOS (5.08 days), reduced costs 40% ($2,362 per day), and decreased mortality (1.01 versus 1.10) for one hospital. Readmissions at 30, 60, and 90 days after a PC consult decreased (61.5%, 47.0%, and 42.1%, respectively). Annual pre- and postprogram referrals to hospice increased (65 to 107). Using modified matched pairs, LOS of PC patients seen within 48 hours of admission average 1.67 days less compared to non-PC patients. LOS for ICU patients with PC services in the ICU within the first 48 hours decreased by 1.12 days. Overall cost avoidance was 1.5 times total cost for PC programs systemwide. One pilot project using a full-time physician in the ICU reduced cost more than $600,000, with 315 saved ICU days, annualized. Systemwide, 69.3% of all referrals to hospice were made by the PC service. CONCLUSION: Early involvement of PC services emerged as advantageous to the net benefit. Given that health care's changing landscape will increasingly include bundled payment and risk holding strategies to improve quality and reduce cost in health care systems, systemwide PC will play a vital role.

Focused vs. Broad enhanced cognitive behavioral therapy for bulimia nervosa with comorbid borderline personality: A randomized controlled trial.

OBJECTIVE: A subset of individuals with bulimia nervosa (BN) have borderline personality disorder (BPD) symptoms, including chronic negative affect and interpersonal problems. These symptoms predict poor BN treatment outcome in some studies. The broad version of Enhanced Cognitive Behavior Therapy (CBT-E) was developed to address co-occurring problems that interfere with treatment response. The current study investigated the relative effects, predictors, and moderators of CBT-E for BN with BPD and co-occurring mood/anxiety disorders. METHOD: Fifty patients with BN and threshold or sub-threshold BPD and current or recent Axis I mood or anxiety disorders were randomly assigned to receive focused CBT-E (CBT-Ef) or broad CBT-E (CBT-Eb) specifically including an interpersonal module and additional attention to mood intolerance. RESULTS: Forty-two percent of the sample reported remission from binge eating and purging at termination. Significant changes across symptom domains were observed at termination and at 6-month follow-up. Though CBT-Ef predicted good outcomes in multivariate models, the severity of affective/interpersonal problems moderated treatment effects: participants with higher severity showed better ED outcomes in CBT-Eb, whereas those with lower severity showed better outcomes in CBT-Ef. Severity of affective/interpersonal BPD symptoms at baseline predicted negative outcomes overall. Follow-up BPD affective/interpersonal problems were predicted by baseline affective/interpersonal problems and by termination EDE score. DISCUSSION: This study supports the utility of CBT-E for patients with BN and complex comorbidity. CBT-Ef appears to be more efficacious for patients with relatively less severe BPD symptoms, whereas CBT-Eb appears to be more efficacious for patients with more severe BPD symptoms.

Perioperative and Anesthetic Considerations in Ebstein's Anomaly.

Ebstein's anomaly is a complex and heterogeneous form of congenital heart disease characterized by malformation and apical displacement of the tricuspid valve leaflets. Patients may present at any time from the neonatal period to adulthood with symptoms ranging from cardiac failure and cyanosis to paroxysmal arrhythmias. Depending on the timing of presentation, various surgical options are available for the management of symptomatic patients. This review will discuss the perioperative and anesthetic management of patients with Ebstein's anomaly with reference to the more common surgical approaches.

Simulation to Assist in the Selection Process of New Airway Equipment in a Children's Hospital.

INTRODUCTION: To provide an informed choice of equipment purchase, we sought to use simulation to allow medical providers an opportunity to evaluate two potential laryngoscopes. METHODS: The study followed a prospective, blinded comparison design. Participants were blinded to the laryngoscope brands by using alphabetic labels on the handles ("A" and "B"). Participants included a convenience sample of healthcare providers who perform intubation. Participants were allowed to perform intubation with the two laryngoscope brands on neonatal, child, and adolescent/adult airway simulators. After practicing with each of the two different laryngoscopes, participants completed an evaluation indicating their preference for one laryngoscope versus the other for each patient age group. RESULTS: Thirty-four healthcare providers participated in the study, including attendings, fellows, nurse practitioners, and transport team members from Neonatology, Pediatric Intensive Care, Anesthesiology, Emergency Medicine, Cardiac Intensive Care, and Otolaryngology. Participants overwhelmingly preferred brand 'A' (89%) over brand 'B' (11%). DISCUSSION: Providers overwhelmingly chose one laryngoscope over the other. Data from this evaluation were used to determine which of the two laryngoscope brands was purchased. Based on our experience, we feel other hospitals should consider the use of simulation to allow providers to examine, compare, and rate medical equipment prior to making purchasing decisions.

Targeting aspirin in acute disabling ischemic stroke: an individual patient data meta-analysis of three large randomized trials.

BACKGROUND: Aspirin is of moderate overall benefit for patients with acute disabling ischemic stroke. It is unclear whether functional outcome could be improved after stroke by targeting aspirin to patients with a high risk of recurrent thrombosis or a low risk of haemorrhage. AIMS: We aimed to determine whether patients at higher risk of thrombotic events or poor functional outcome, or lower risk of major haemorrhage had a greater absolute risk reduction of poor functional outcome with aspirin than the average patient. METHODS: We used data on individual ischemic stroke patients from three large trials of aspirin vs. placebo in acute ischemic stroke: the first International Stroke Trial (n = 18,372), the Chinese Acute Stroke Trial (n = 20,172) and the Multicentre Acute Stroke Trial (n = 622). We developed and evaluated clinical prediction models for the following: early thrombotic events (myocardial infarction, ischemic stroke, deep vein thrombosis and pulmonary embolism); early haemorrhagic events (significant intracranial haemorrhage, major extracranial haemorrhage, or haemorrhagic transformation of an infarct); and late poor functional outcome. We calculated the absolute risk reduction of poor functional outcome (death or dependence) at final follow-up in: quartiles of early thrombotic risk; quartiles of early haemorrhagic risk; and deciles of poor functional outcome risk. RESULTS: Ischemic stroke patients who were older, had lower blood pressure, computerized tomography evidence of infarct or more severe deficits due to stroke had increased risk of thrombotic and haemorrhagic events and poor functional outcome. Prediction models built with all baseline variables (including onset to treatment time) discriminated weakly between patients with and without recurrent thrombotic events (area under the receiver operating characteristic curve 0·56, 95% CI:0·53-0·59) and haemorrhagic events (0·57, 0·52-0·64), though well between patients with and without poor functional outcome (0·77, 0·76-0·78) in the International Stroke Trial. We found no evidence that the net benefit of aspirin increased with increasing risk of thrombosis, haemorrhage or poor functional outcome in all three trials. CONCLUSIONS: Using simple clinical variables to target aspirin to patients after acute disabling stroke by risk of thrombosis, haemorrhage or poor functional outcome does not lead to greater net clinical benefit. We suggest future risk stratification schemes include new risk factors for thrombosis and intracranial haemorrhage.

Gender differences in clinical trials of binge eating disorder: An analysis of aggregated data.

OBJECTIVE: The aim of the study was to examine gender differences in baseline and outcome variables in clinical trials for binge eating disorder (BED). METHOD: Data from 11 randomized controlled psychosocial treatment studies were aggregated (N = 1,325: 208 male, 1,117 female). Baseline and outcome symptoms were assessed via the interview and questionnaire versions of the Eating Disorder Examination (EDE). Multilevel analyses were conducted investigating gender differences at baseline and posttreatment, defined as EDE scores, objective binge episode (OBE) reduction, and OBE remission at termination. RESULTS: Few males from low socioeconomic status or minority groups participated in the outcome studies. Males reported significantly lower EDE global, shape, weight, and eating concerns at baseline. No main effects of gender were found in treatment outcome scores when controlling for baseline differences; however, baseline EDE global score (which showed gender differences at baseline) and OBEs directly predicted outcome for both males and females. A significant interaction between gender, treatment length, and shape/weight concerns indicated that males with lower shape/weight concerns achieved OBE remission in shorter treatments, whereas men with high shape/weight concerns and women with either high or low shape/weight concerns were more likely to achieve OBE remission in treatments of longer duration. CONCLUSIONS: These results suggest BED treatment studies must improve their recruitment of men and appeal to men with lower shape/weight concerns. Additionally, longer term treatments, although more efficacious for women and men with more severe shape/weight concerns, may not be necessary for men with low shape/weight concerns. (PsycINFO Database Record