The Association of the Lactate-Albumin Ratio With Mortality and Multiple Organ Dysfunction in PICU Patients.

OBJECTIVES: To compare the relative associations of lactate, albumin, and the lactate-albumin ratio (LAR) measured early in disease course against mortality and prevalence of multiple organ dysfunction syndrome (MODS) in a general sample of critically ill pediatric patients. DESIGN: Retrospective analysis of the Health Facts (Cerner Corporation, Kansas City, MO) national database. SETTING: U.S. hospitals with PICUs. PATIENTS: Children admitted to the ICU ( n = 648) from 2009 to 2018 who had lactate and albumin measured within 6 hours of admission. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 648 admissions were included, with an overall mortality rate of 10.8% ( n = 70) and a MODS prevalence of 29.3% ( n = 190). Compared with survivors, deaths had higher initial lactates (7.3 mmol/L [2.6-11.7 mmol/L] vs 1.9 mmol/L [1.2-3.1 mmol/L]; p < 0.01), lower initial albumins (3.3 g/dL [2.7-3.8 g/dL] vs 4.2 g/dL [3.7-4.7 g/dL]; p < 0.01), and higher LARs (2.2 [1.0-4.2] vs 0.5 [0.3-0.8]; p < 0.01), with similar trends in patients with MODS versus those without MODS. LAR demonstrated a higher odds ratio (OR) for death than initial lactate alone (2.34 [1.93-2.85] vs 1.29 [1.22-1.38]) and a higher OR for MODS than initial lactate alone (2.10 [1.73-2.56] vs 1.22 [1.16-1.29]). Area under the receiver operating characteristic (AUROC) curve of LAR for mortality was greater than initial lactate (0.86 vs 0.82; p < 0.01). The LAR AUROC for MODS was greater than the lactate AUROC (0.71 vs 0.66; p < 0.01). Trends of lactate, albumin, and LAR for mortality were consistent across several diagnostic subgroups (trauma, primary respiratory failure, toxicology), but not all. CONCLUSIONS: LAR measured early in the course of critical illness is significantly associated with mortality and development of MODS when compared with initial lactate or initial albumin alone in critically ill pediatric patients.

Pediatric Critical Care-Associated Parental Traumatic Stress: Beyond the First Year.

OBJECTIVES: Perform a longitudinal analysis of parental traumatic stress up to 30 months after PICU discharge. DESIGN: Prospective observational cohort study. SETTING: Two tertiary care children's hospitals with mixed medical/surgical/cardiac PICUs. SUBJECTS: Parents of patients unexpectedly admitted to the PICU. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Two hundred sixty-five parents of 188 children were enrolled. Of the 195 parents who completed the 3-9-month assessments, 29 (14.8%) met posttraumatic stress disorder (PTSD) qualification on the PTSD Symptom Scale Interview for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Multivariable analysis showed parents who met acute stress disorder (ASD) qualification (odds ratio [OR] 8.01; 95% CI 2.64-24.3), parents of children with Pediatric Overall Performance Category score of severe or coma at discharge (OR 5.21; 95% CI 1.65-16.4), parents who had concerns for their child's permanent injury (OR 1.82; 95% CI 1.36-2.43), and parents who reported increased knowledge of child illness during admission (OR 1.82; 95% CI 1.13-2.93) had increased odds of developing parental PTSD. Of the 175 parents (66%) who completed the 18-30-month assessments, 22 (12.5%) met PTSD qualification. Multivariable analysis showed parents who met ASD qualification (OR 4.19; 95% CI 1.12-15.7), parents who had a history of a family member or themselves being admitted to ICU (OR 6.51; 95% CI 1.43-29.6), and parents who had concerns of child's susceptibility to death post discharge (OR 1.58; 95% CI 1.19-2.09) had increased odds of developing parental PTSD. At 18-30 months post discharge, parents who met the PTSD qualification were more likely to report a decrease in household income following discharge (OR 9.23; 95% CI 1.71-49.9). CONCLUSIONS: Parental PTSD remains a significant morbidity of PICU admission for a subgroup of parents greater than 18 months post admission. Identifiable risk factors will inform the development of targeted interventions.

Effect of the coronavirus disease 2019 pandemic on morbidity among children hospitalized for an asthma exacerbation.

BACKGROUND: Pediatric asthma exacerbations account for substantial morbidity, including emergency department (ED) visits and hospitalizations. Although the coronavirus disease 2019 (COVID-19) pandemic was associated with a decrease in pediatric asthma ED visits and hospitalizations, there is limited information on the clinical characteristics of children hospitalized with an asthma exacerbation during the pandemic. OBJECTIVE: To investigate the clinical characteristics of children hospitalized with an asthma exacerbation during the pandemic as compared with those hospitalized during the same months in the year prior. METHODS: A retrospective case-control study was conducted at the Children's National Hospital, Washington, DC, comparing demographic and clinical characteristics of all children, 2 to 18 years old, hospitalized for an asthma exacerbation between April to September 2020 (cases) and April to September 2019 (controls). RESULTS: We identified 50 cases and 243 controls. Cases were significantly older than controls (9.8 ± 4.3 years vs 6.7 ± 3.8 years; P < .001), had significantly less eczema (16% vs 32.1%; P = .02) and food allergies (6% vs 18.5%; P = .03), and were more noncompliant with controller medications (46% vs 24.7%; P = .002) than controls. Magnesium sulfate was more frequently administered in the ED to the cases than to the controls (84% vs 63%; P = .004). Its use was associated with older age, African American race, and Hispanic ethnicity, but was independent of comorbid conditions. CONCLUSION: Patients hospitalized for asthma during the COVID-19 pandemic were older and have less atopy than those hospitalized prepandemic. A larger proportion received magnesium sulfate in the ED, suggesting patients had with more severe asthma presentation during the pandemic.

Pharmacogenetic and clinical predictors of ondansetron failure in a diverse pediatric oncology population.

PURPOSE: Chemotherapy-induced nausea and vomiting (CINV) is a frequently seen burdensome adverse event of cancer therapy. The 5-HT3 receptor antagonist ondansetron has improved the rates of CINV but, unfortunately, up to 30% of patients do not obtain satisfactory control. This study examined whether genetic variations in a relevant drug-metabolizing enzyme (CYP2D6), transporter (ABCB1), or receptor (5-HT3) were associated with ondansetron failure. METHODS: DNA was extracted from blood and used to genotype: ABCB1 (3435C > T (rs1045642) and G2677A/T (rs2032582)), 5-HT3RB (rs3758987 T > C and rs45460698 (delAAG/dupAAG)), and CYP2D6 variants. Ondansetron failure was determined by review of the medical records and by patient-reported outcomes (PROs). RESULTS: One hundred twenty-nine patients were approached; 103 consented. Participants were less than 1 to 33 years (mean 6.85). A total of 39.8% was female, 58.3% was White (22.3% Black, 19.4% other), and 24.3% was Hispanic. A majority had leukemia or lymphoma, and 41 (39.8%) met the definition of ondansetron failure. Of variants tested, rs45460698 independently showed a significant difference in risk of ondansetron failure between a mutant (any deletion) and normal allele (p = 0.0281, OR 2.67). Age and BMI were both predictive of ondansetron failure (age > 12 (OR 1.12, p = 0.0012) and higher BMI (OR 1.13, p = 0.0119)). In multivariate analysis, age > 12 was highly predictive of ondansetron failure (OR 7.108, p = 0.0008). rs45460698 was predictive when combined with an increased nausea phenotype variant of rs1045642 (OR 3.45, p = 0.0426). CONCLUSION: Select phenotypes of 5-HT3RB and ABCB1, age, and potentially BMI can help predict increased risk for CINV in a diverse pediatric oncology population.

Alterations in cardiac output in fetuses with congenital heart disease.

OBJECTIVE: Fetuses with severe congenital heart disease (CHD) have altered blood flow patterns. Prior work to assess fetal combined cardiac output (CCO) is limited by sample size and lack of longitudinal gestational data. Our aim was to evaluate CCO in CHD fetuses to determine whether the presence of single ventricle (SV) physiology or aortic obstruction impacts fetal blood flow and cardiovascular hemodynamics. METHOD: Prospective study including singleton fetuses with CHD (n = 141) and controls (n = 118) who underwent a mid- and late-gestation fetal echocardiogram. Ventricular cardiac output was calculated using the standard computation. Combined cardiac output was derived as the sum of the right and left cardiac outputs and indexed to estimated fetal weight. RESULTS: Fetuses with two ventricle (2V) CHD had significantly higher CCO compared to controls and SV CHD fetuses. Fetuses with SV-CHD had similar CCO compared to controls. Fetuses with 2V-CHD and aortic obstruction had significantly higher CCO than fetuses with SV-CHD and aortic obstruction. CONCLUSION: Our findings suggest that the SV can compensate and increase CCO despite the lack of a second functioning ventricle, however, the degree of compensation may be insufficient to support the increased blood flow needed to overcome the hemodynamic and physiologic alternations seen with severe CHD.

Early Versus Late Brain Magnetic Resonance Imaging after Neonatal Hypoxic Ischemic Encephalopathy Treated with Therapeutic Hypothermia.

OBJECTIVE: To evaluate the agreement in brain injury findings between early and late magnetic resonance imaging (MRI) in newborn infants with hypoxic-ischemic encephalopathy treated with therapeutic hypothermia and to compare the ability of early vs late MRI to predict early neurodevelopmental outcomes. STUDY DESIGN: This was a prospective longitudinal study of 49 patients with hypoxic-ischemic encephalopathy who underwent therapeutic hypothermia and had MRI performed at both <7 and ≥7 days of age. MRIs were reviewed by an experienced neuroradiologist and assigned brain injury severity scores according to established systems. Scores for early and late MRIs were assessed for agreement using the kappa statistic. The ability of early and late MRI scores to predict death or developmental delay at 15-30 months of age was assessed by logistic regression analyses. RESULTS: Agreement between the early and late MRI was substantial to near perfect (k > 0.75, P < .001) across MRI scoring systems. In cases of discrepant scoring, early MRI was more likely to identify severe injury when compared with late MRI. Early MRI scores were more consistently predictive of adverse outcomes compared with late MRI. CONCLUSIONS: The results of this study suggest that a single MRI performed in the first week after birth is adequate to assess brain injury and offer prognostic information in this high-risk population.

Serial plasma biomarkers of brain injury in infants with neonatal encephalopathy treated with therapeutic hypothermia.

BACKGROUND: Neonatal encephalopathy (NE) is a major cause of long-term neurodevelopmental disability in neonates. We evaluated the ability of serially measured biomarkers of brain injury to predict adverse neurological outcomes in this population. METHODS: Circulating brain injury biomarkers including BDNF, IL-6, IL-8, IL-10, VEGF, Tau, GFAP, and NRGN were measured at 0, 12, 24, 48, 72, and 96 h of cooling from 103 infants with NE undergoing TH. The biomarkers' individual and combinative ability to predict death or severe brain injury and adverse neurodevelopmental outcomes beyond 1 year of age was assessed. RESULTS: Early measurements of inflammatory cytokines IL-6, 8, and 10 within 24 HOL (AUC = 0.826) and late measurements of Tau from 72 to 96 HOL (AUC = 0.883, OR 4.37) were accurate in predicting severe brain injury seen on MRI. Late measurements of Tau were predictive of adverse neurodevelopmental outcomes (AUC = 0.81, OR 2.59). CONCLUSIONS: Tau was consistently a predictive marker for brain injury in neonates with NE. However, in the first 24 HOL, IL-6, 8, and 10 in combination were most predictive of death or severe brain injury. The results of this study support the use of a serial biomarker panel to assess brain injury over the time course of disease in NE. IMPACT: While recent studies have evaluated candidate brain injury biomarkers, no biomarker is in current clinical use. This study supports the use of a serial biomarker panel for ongoing assessment of brain injury neonates with NE. In combination, IL6, IL8, and IL10 in the first 24 h of cooling were more predictive of brain injury by MRI than each cytokine alone. Individually, Tau was overall most consistently predictive of adverse neurological outcomes, particularly when measured at or after rewarming.

Effect of Cognitive and Physical Rest on Persistent Postconcussive Symptoms following a Pediatric Head Injury.

OBJECTIVE: To evaluate the effect of cognitive and physical rest on persistent postconcussive symptoms in a pediatric population. STUDY DESIGN: A prospective cohort study of 5- to 18-year-olds diagnosed with an acute concussion in a tertiary care pediatric emergency department was conducted from December 2016 to May 2019. Participants (n = 119) were followed over 1 month to track days off from school and sports and the development of persistent postconcussive symptoms (residual concussion symptoms beyond 1 month). Participants were dichotomized into minimal (≤2) and moderate (>2) rest, based on days off from school and sports after a concussion. Univariate and multivariable logistic regression analyses were completed to examine associations with persistent postconcussive symptoms. RESULTS: Of the participants in our study, 24% had persistent postconcussive symptoms. Adolescent age, history of prolonged concussion recovery, and headache at presentation were associated with higher odds of persistent postconcussive symptoms in univariate analyses. In a multivariable logistic regression model, only adolescent age was associated with increased odds of persistent postconcussive symptoms. Compared with the minimal cognitive rest group, moderate cognitive rest did not decrease the odds of persistent postconcussive symptoms (aOR, 1.15; 95% CI, 0.44-2.99). Compared with the minimal physical rest group, moderate physical rest also did not decrease the odds of persistent postconcussive symptoms (aOR, 3.17; 95% CI, 0.35-28.78). CONCLUSIONS: Emerging evidence supports early return to light activity for recovery of acute pediatric concussion. Our study adds to this management approach as we did not find that rest from school and sports resulted in a decreased odds of persistent postconcussive symptoms.

Impact of protein-losing enteropathy in children who underwent the Fontan operation.

Previous reports have identified risk factors associated with development of post-Fontan protein-losing enteropathy. Less is known about the economic impact and resource utilisation required for post-Fontan protein-losing enteropathy in the current era. We conducted a single-centre retrospective study to assess the impact of post-Fontan protein-losing enteropathy on transplant-free survival. We also described resource utilisation and treatment variations among post-Fontan protein-losing enteropathy patients. Children who received care at our centre between 2009 and 2017 after the Fontan surgery were eligible. Initial admissions for the Fontan operative procedure were excluded. Demographics, hospital admissions, resource utilisation, medications and charges were reviewed. Patients were divided into two groups based on the presence of post-Fontan protein-losing enteropathy. Of the 343 patients screened, 147 met the eligibility criteria. Of these, 28 (19%) developed protein-losing enteropathy. After adjusting for follow-up duration, the protein-losing enteropathy group had higher number of encounters (2.15 ± 2.16 versus 1.47 ± 2.56, p 0.002), hospital length of stay (days) (25 ± 51.3 versus 11.4 ± 41.7, p < 0.0001) and total charges (2018US$) (388,489 ± 759,859 versus 202,725 ± 1,076,625, p < 0.0001). Encounters for patients with protein-losing enteropathy utilised more therapies. Among those with protein-losing enteropathy, use of digoxin was associated with slightly decreased odds for mortality and/or transplant (0.95, confidence interval 0.90-0.99, p 0.021). The 10-year transplant-free survival for patients with/without protein-losing enteropathy was 65.7/97.3% (p 0.002), respectively. Post-Fontan protein-losing enteropathy is associated with reduced 10-year transplant-free survival, higher resource utilisation, charges and medication use compared with the non-protein-losing enteropathy group. Practice variation among post-Fontan protein-losing-enteropathy patients is common. Further larger studies are needed to assess the impact of standardisation on the well-being of children with post-Fontan protein-losing enteropathy.

Temporal trends in patient referral for Transcatheter aortic valve replacement and reasons for exclusion at a high-volume Center in the United States.

BACKGROUND: Clinical indications for transcatheter aortic valve replacement (TAVR) and elements of the implantation procedure, including delivery system miniaturization and novel access options, have evolved over time. The reasons patients are excluded from TAVR also have changed. The impact of these changes on patient referral for and exclusion from TAVR is unknown. METHODS: We retrospectively analyzed patients referred to our center for TAVR from January 2010 to August 2016 to evaluate reasons for patient exclusion. Patients were divided into three groups based on initial screening date for trends in demographics and exclusion: Group 1, 2010-2012; Group 2, 2012-2014; Group 3, 2014 to August 1, 2016. Annual trends for patient exclusion from TAVR were assessed. RESULTS: One thousand nine hundred fifty-three patients were referred and underwent screening for TAVR. The rates at which patients were referred for TAVR were 23.8, 25.9, and 24.5 per month in groups 1, 2, and 3, respectively. Rate of patient exclusion from TAVR decreased from 68% in Group 1 to 38% in Group 3 (P < .001). The largest percentage of patients (29.4%) were initially excluded from TAVR for cardiac reasons, but this trend has decreased over time. Twenty-five percent are excluded for lack of procedural indication. Exclusion from TAVR for vascular access reasons decreased from 7.9% in 2010 to 1.0% in 2016 (P = .017). CONCLUSIONS: Referral numbers have been robust since TAVR became available. The percentage of patients excluded from TAVR has decreased over time. Patients are most commonly excluded from TAVR for concomitant coronary artery disease (CAD), asymptomatic severe AS, moderate AS, or non-cardiac critical illness. Patients with CAD and those with asymptomatic severe AS or moderate AS should be a focus for continued research in TAVR.

Predicted magnitude of alternate access in the contemporary transcatheter aortic valve replacement era.

OBJECTIVES: We aimed to evaluate the true extent of alternate access in a contemporary cohort of transcatheter aortic valve replacement (TAVR) patients. BACKGROUND: Appropriate access selection for TAVR impacts clinical outcomes. Despite device miniaturization, some patients remain ineligible for transfemoral arterial access. METHODS: Five hundred seventy-five consecutive TAVR patients were classified according to iliofemoral artery diameters measured by computed tomography (<5.0 mm, 5.0-5.4 mm, 5.5-5.9 mm, or ≥6 mm) and need for alternate access rate was estimated according to commercially available transcatheter heart valve Instructions For Use (IFU). RESULTS: Based on iliofemoral artery diameters alone, 11.5% of patients were predicted to require alternate access. After patient-level adjustment for the size of the planned THV and severe tortuosity or severe calcification, 14.9% and 20.8% of patients, respectively were predicted to require alternate access. Overall, 87.8% of patients underwent transfemoral TAVR and 12.3% underwent alternate access. There was no difference in the rate of major vascular complications and life threatening or major bleeding between groups, but transfusion rate was higher in smaller vessel groups. CONCLUSIONS: Despite device miniaturization, a substantial minority of contemporary TAVR patients still require alternate access. Most are eligible for newer extrathoracic approaches including transcaval, subclavian, and transcarotid that avoid the morbidity of transthoracic access.

Impact of right ventricular function on outcome of severe aortic stenosis patients undergoing transcatheter aortic valve replacement.

BACKGROUND: Right ventricular (RV) dysfunction was shown to be associated with adverse outcomes in a variety of cardiac patients and is considered a risk factor for adverse outcome according to the updated Valve Academic Research Consortium criteria. OBJECTIVE: Our goal was to assess the impact of RV function at baseline on 1-year mortality among patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR). METHODS: All patients with severe AS treated with TAVR from May 2007 to March 2015 at our center were included in the present study, and baseline and procedural characteristics were recorded for each patient. The patients were categorized according to RV function at baseline as assessed by current guidelines, and a comparison of mortality rates up to 1 year was performed. RESULTS: Among 650 patients, 606 had adequate echocardiogram quality and 146 (24%) had RV dysfunction. There were significant differences between the 2 groups, as patients with RV dysfunction were younger (81±9 vs 84±7 years, P=.01) and were more likely to be male (65% vs 42%, P<.001). In addition, patients with RV dysfunction had higher rates of prior myocardial infarction (26% vs 16%, P=.02) and atrial fibrillation (51% vs 39%, P=.02). Echocardiographic parameters demonstrated higher rates of left ventricular ejection fraction <40% (40% vs 18%, P<.001), tricuspid regurgitation above moderate (16% vs 9%, P=.04), and higher pulmonary artery systolic pressure (50±17 vs 44±16 mm Hg, P<.001) among patients with severe AS and RV dysfunction compared with patients with normal RV function. Despite the unfavorable cardiac function, patients with severe AS undergoing TAVR have similar functional class (P=.22) and mortality rates at 1year (27% vs 23%, log-rank P=.45). CONCLUSIONS: Patients with severe AS and RV dysfunction have similar 1-year mortality and functional class after TAVR to patients with normal RV function. The presence of RV dysfunction does not correlate with outcome in patients with severe AS.

Comparison of transradial and transfemoral access in patients undergoing percutaneous coronary intervention for complex coronary lesions.

OBJECTIVE: Comparison of transradial versus transfemoral access for complex percutaneous coronary intervention (PCI) with regard to both complications and long-term outcomes. BACKGROUND: Radial access has been shown to confer superior results in patients undergoing PCI, especially in patients with acute coronary syndromes. However, radial access has limitations of sheath and device size, which may increase procedure time and result in inferior outcomes. METHODS: Patients undergoing PCI for complex lesions, defined as type C according the ACC/AHA classification system, were included in this study. Propensity matching was performed to adjust for differences in baseline characteristics. Transradial patients were then compared to transfemoral patients in regard to procedural, in-hospital, and 6-month outcomes. RESULTS: Among 2142 patients with 2591 lesions treated, 1876 had femoral access and 267 had radial access. Radial access patients were more likely to be male (75% vs. 66%, P = 0.003) and less likely to present with acute myocardial infarction (27% vs. 42%, P < 0.001). Procedural characteristics demonstrated lower use of heparin in the femoral group (17% vs. 73%, P < 0.001) with similarly low use of glycoprotein inhibitors (5.6% vs. 3.4%, P = 0.14). Patients in the femoral group had higher rates of transfusions (3.7% vs. 0%, P = 0.004) and vascular complications (1.7% vs. 0%, P = 0.03). Following propensity matching, there was no difference in mid-term outcomes between radial and femoral groups. CONCLUSIONS: In patients with complex coronary lesions undergoing PCI, the radial approach demonstrates similar mid-term outcomes as the femoral approach with a potentially lower rate of complications. © 2016 Wiley Periodicals, Inc.

Contemporary transcatheter aortic valve replacement with third-generation balloon-expandable versus self-expanding devices.

OBJECTIVES: To evaluate balloon-expandable and self-expanding third-generation transcatheter aortic valve replacement (TAVR) devices according to patient selection criteria and outcomes. BACKGROUND: Two competing third-generation TAVR technologies are currently commercially available in the US. There are no published head-to-head comparisons of the relative performance of these two devices. METHODS: 257 consecutive patients undergoing TAVR with a third-generation balloon-expandable (Edwards Sapien 3) or self-expanding device (Medtronic CoreValve Evolut R) at a single US medical center were included. Choice of TAVR device was at the discretion of the multidisciplinary Heart Team. Baseline clinical characteristics, echocardiographic and CT imaging, procedural and 30-day outcomes were prospectively collected. RESULTS: 74 patients received a self-expanding valve (SEV) and 183 received a balloon-expandable valve (BEV). Patients selected for SEV were more frequently women, with lower body surface area and smaller calcified iliofemoral arteries. Three SEV patients required implantation of a second valve to successfully treat paravalvular leak. Only one BEV patient had moderate paravalvular regurgitation. There was no difference in the rate of stroke, major vascular complication or bleeding. Permanent pacemaker implantation rate was significantly higher with SEV (12.7% vs 4.7%, P = 0.49) and hospital length of stay was longer (8.3% vs 6.5%, P = 0.043), but 30-day mortality was comparable (1.4% vs 1.6%, P = 1.00). CONCLUSIONS: Short-term outcomes were equivalent between the two technologies. Clinically significant paravalvular regurgitation was rare. SEV were more frequently selected in women and patients with challenging transfemoral access, but were associated with higher permanent pacemaker implantation rate and longer hospital length of stay.

Clinical profiles and correlates of mortality in nonagenarians with severe aortic stenosis undergoing transcatheter aortic valve replacement.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) is the current standard for nonoperable and high-risk surgical patients with aortic stenosis, including those of advanced age. However, the clinical profiles, procedural characteristics, and outcomes of nonagenarians undergoing TAVR have not been thoroughly reported. METHODS: A total of 654 patients (n = 107 >90 years old and n = 547 <90 years) with severe aortic stenosis undergoing TAVR were included in this analysis. Baseline characteristics, procedural variables, and in-hospital outcomes and complications at 30 days and 12 months were analyzed. RESULTS: Overall, of the patients included, 46% were high risk and 53% inoperable. Although nonagenarians had a higher Society of Thoracic Surgeons score of 9.2 ± 4 (12.1 ± 4 vs 8.6 ± 4, P < .001), other factors were considerably lower in this group: diabetes (22% vs 36%, P = .008), hyperlipidemia (65% vs 83%, P < .001), prior coronary artery bypass (13% vs 39%, P < .001), and mean body mass index (24.5 ± 5 vs 28.1 ± 7 kg/m(2), P < .001). The correlates for 1-year mortality in nonagenarians were as follows: ≥moderate aortic insufficiency post-TAVR (hazard ratio [HR] 5.07, 95% CI 1.17-22, P = .03), pacemaker implantation after TAVR (HR 6.87, 95% CI 2.32-20.3, P = .001), and peripheral vascular disease (HR 2.35, 95% CI 1.03-5.38, P = .042). Mortality at 30 days (12.1% vs 7.1%, P = .07) and at 1 year (25% vs 21%, P = .35) was similar between groups. CONCLUSION: Nonagenarians undergoing TAVR had a healthier clinical profile compared with younger patients. Age alone should not be a discriminatory factor when screening elderly patients with aortic stenosis because even the nonagenarians are doing well when compared with the younger elderly population. Transcatheter aortic valve replacement remains a viable option for the treatment of severe symptomatic aortic stenosis for the elderly regardless of their age.

Impact of baseline mitral regurgitation on short- and long-term outcomes following transcatheter aortic valve replacement.

BACKGROUND: The prevalence of concomitant significant mitral regurgitation (MR) in patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR) ranges from 2% to 33%. The impact of significant MR on post-TAVR outcomes remains controversial. METHODS: The data from a cohort of patients with symptomatic severe AS undergoing TAVR at out institution were retrospectively analyzed. The last transthoracic echocardiogram (TTE) before the index TAVR procedure was selected as the baseline assessment of the degree of MR. The total study cohort (N = 589) was divided into 2 groups: significant ≥moderate MR (n = 68) versus nonsignificant

Theta-Alpha Variability on Admission EEG Is Associated With Outcome in Pediatric Cerebral Malaria.

PURPOSE: Pediatric cerebral malaria has high rates of mortality and neurologic morbidity. Although several biomarkers, including EEG, are associated with survival or morbidity, many are resource intensive or require skilled interpretation for clinical use. Automation of quantitative interpretation of EEG may be preferable in resource-limited settings, where trained interpreters are rare. As currently used quantitative EEG factors do not adequately describe the spectrum of variability seen in studies from children with cerebral malaria, the authors developed and validated a new quantitative EEG variable, theta-alpha variability (TAV). METHODS: The authors developed TAV, a new quantitative variable, as a composite of multiple automated EEG outputs. EEG records from 194 children (6 months to 14 years old) with cerebral malaria were analyzed. Independent EEG interpreters performed standard quantitative and qualitative analyses, with the addition of the newly created variable. The associations of TAV with other quantitative EEG factors, a qualitative assessment of variability, and outcomes were assessed. RESULTS: Theta-alpha variability was not highly correlated with alpha, theta, or delta power and was not associated with qualitative measures of variability. Children whose EEGs had higher values of TAV had a lower risk of death (odds ratio = 0.934, 95% confidence interval = 0.902-0.966) or neurologic sequelae (odds ratio = 0.960, 95% confidence interval = 0.932-0.990) compared with those with lower values. Receiver operating characteristic analysis in predicting death at a TAV threshold of 0.244 yielded a sensitivity of 74% and specificity of 70% for an area under the receiver operating characteristic curve of 0.755. CONCLUSIONS: Theta-alpha variability is independently associated with outcome in pediatric cerebral malaria and can predict death with high sensitivity and specificity. Automated determination of this newly created EEG factor holds promise as a potential method to increase the clinical utility of EEG in resource-limited settings by allowing interventions to be targeted to those at higher risk of death or disability.

Pain Frequency and Health Care Utilization Patterns in Women with Sickle Cell Disease Experiencing Menstruation-Associated Pain Crises.

Background: Pain crises in sickle cell disease (SCD) lead to high rates of health care utilization. Historically, women have reported higher pain burdens than men, with recent studies showing a temporal association between pain crisis and menstruation. However, health care utilization patterns of SCD women with menstruation-associated pain crises have not been reported. We studied the frequency, severity, and health care utilization of menstruation-associated pain crises in SCD women. Materials and Methods: A multinational, cross-sectional cohort study of the SCD phenotype was executed using a validated questionnaire and medical chart review from the Consortium for the Advancement of Sickle Cell Research (CASiRe) cohort. Total number of pain crises, emergency room/day hospital visits, and hospitalizations were collected from a subcohort of 178 SCD women within the past 6 months and previous year. Results: Thirty-nine percent of women reported menstruation-associated pain crises in their lifetime. These women were significantly more likely to be hospitalized compared with those who did not (mean 1.70 vs. 0.67, p = 0.0005). Women reporting menstruation-associated pain crises in the past 6 months also experienced increased hospitalizations compared with those who did not (mean 1.71 vs. 0.75, p = 0.0016). Forty percent of women reported at least four menstruation-associated pain crises in the past 6 months. Conclusions: Nearly 40% of SCD women have menstruation-associated pain crises. Menstruation-associated pain crises are associated with high pain burden and increased rates of hospitalization. Strategies are needed to address health care disparities within gynecologic care in SCD.

Comfort with Pharmacogenetic Testing Amongst Pediatric Oncology Providers and Their Patients.

Background: Pharmacogenetic (PGx) testing, a component of personalized medicine, aims to ensure treatment efficacy while reducing side effects and symptoms. Before this testing becomes routine in the pediatric oncology population, nurses need to understand the knowledge and concerns of providers, patients, and family members with regard to the timing, extent, interpretation, and incorporation of PGx testing. Methods: As part of a comprehensive PGx study (larger study) for children diagnosed with cancer, we surveyed providers and caregivers of children with cancer about their knowledge of and comfort with PGx testing. Caregivers who declined to participate in the larger PGx study were also asked to participate in the survey. Chi-square tests and a two-sample t-test were used to compare variables. Results: One hundred and two participants from the larger PGx study and 12 families who refused (response rate of 77% and 54%, respectively) as well as 29 providers (88%) completed surveys. Families not on the study were less interested in and comfortable with PGx results. Both groups were concerned about health or life insurance discrimination and payment. Providers would like support in ordering PGx testing and interpreting PGx. Discussion: Providers remain wary of most PGx testing, uncomfortable with interpreting and applying the results. Families are interested in the possibilities of personalized prescribing while worried about who has access to their child's genetic information. Further education on relevant tests for providers, including nurses, and the testing process for families, including details on privacy and sharing of genetic information, appear necessary.

Using EEG in Resource-Limited Areas: Comparing Qualitative and Quantitative Interpretation Methods in Cerebral Malaria.

BACKGROUND: Our goal was to compare the strength of association and predictive ability of qualitative and quantitative electroencephalographic (EEG) factors with the outcomes of death and neurological disability in pediatric cerebral malaria (CM). METHODS: We enrolled children with a clinical diagnosis of CM admitted to Queen Elizabeth Central Hospital (Blantyre, Malawi) between 2012 and 2017. A routine-length EEG was performed within four hours of admission. EEG data were independently interpreted using qualitative and quantitative methods by trained pediatric neurophysiologists. EEG interpreters were unaware of patient discharge outcome. RESULTS: EEG tracings from 194 patients were reviewed. Multivariate modeling revealed several qualitative and quantitative EEG variables that were independently associated with outcomes. Quantitative methods modeled on mortality had better goodness of fit than qualitative ones. When modeled on neurological morbidity in survivors, goodness of fit was better for qualitative methods. When the probabilities of an adverse outcome were calculated using multivariate regression coefficients, only the model of quantitative EEG variables regressed on the neurological sequelae outcome showed clear separation between outcome groups. CONCLUSIONS: Multiple qualitative and quantitative EEG factors are associated with outcomes in pediatric CM. It may be possible to use quantitative EEG factors to create automated methods of study interpretation that have similar predictive abilities for outcomes as human-based interpreters, a rare resource in many malaria-endemic areas. Our results provide a proof-of-concept starting point for the development of quantitative EEG interpretation and prediction methodologies useful in resource-limited settings.