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Objective/background: Behavioral Sleep Interventions (BSI) is an efficacious class of treatment approaches for infant sleep disturbance. Little is known about BSI implementation in the real world. Objectives were to a) examine the prevalence of BSI implementation and related factors in a diverse sample of US mothers; b) assess racial-ethnic group differences; and c) examine predictors of BSI implementation., Participants: Participants included mothers ( n = 353) with an infant (6-18 months) from one of the three racial-ethnic groups: White Hispanic ( n = 113), White non-Hispanic ( n = 122), Black non-Hispanic ( n = 118)., Methods: Respondents completed an online survey assessing BSI implementation, familiarity, barriers, sleep knowledge, cognitions, and sleep patterns., Results: Approximately one-third (36%) of the sample endorsed BSI implementation and 59% reported BSI familiarity. Black non-Hispanic mothers were more likely to report stopping a BSI prior to completion (OR = 4.92, p <.05) and more likely to hear about BSI from a health-care professional (OR = 1.32, p <.05) compared to White non-Hispanic mothers. Racial-ethnic group differences were identified for a variety of sleep practices, including bedsharing, independent sleep onset, and score on a validated measure of problematic sleep. No racial-ethnic group differences were found in BSI implementation, cognitions, or barriers. BSI implementation was predicted by BSI familiarity, more maternal education, and cognitions around infant self-soothing., Conclusions: Differential BSI implementation does not appear to be a major driver of sleep disparities, although Black non-Hispanic mothers who decide to implement BSI do report notably lower completion rates. Future studies should examine alternative mechanisms of sleep disparities as well as strategies to promote sleep health in diverse families.

Objective: While previous studies regarding neonatal home feeding regimens have demonstrated a more favorable prognosis for nasogastric (NG) versus gastrostomy tubes (GT), institutional practices of discharge on NG feeds are varied, particularly for infants with bronchopulmonary dysplasia (BPD). Little is known regarding the risk factors for patients treated with GT postdischarge in premature infants with BPD. Our objective was to identify frequency and risk factors for treating premature infants with BPD discharged on NG feeds with GT., Study Design: In this retrospective study, we included infants born at 30 weeks' gestational age with BPD transitioning from a tertiary care center to home on NG feeds from 2010 to 2016., Results: Of the 86 infants included in this study, 25 (29%) underwent GT placement at a median age of 264 days postdischarge. Fourteen (56%) were able to remove the GT at a median age of 979.5 days. Infants not requiring GT placement postdischarge were found to have a significantly higher ccipitofrontal circumference ( p  = 0.0089) and length ( p  = 0.0166) at discharge compared with infants with GT., Conclusion: NG feeding for infants with BPD appears to be a viable treatment with fewer patients (29%) requiring GT placement. Gestational age and abnormal magnetic resonance imaging results were found to have a significant association with GT placement postdischarge., Competing Interests: None declared., (Thieme. All rights reserved.)

Rationale: Little is known on the use of noninvasive ventilation (NIPPV) in pediatric hematopoietic cell transplant (HCT) patients., Objective: We sought to describe the landscape of NIPPV use and to identify risk factors for failure to inform future investigation or quality improvement., Methods: This is a multicenter, retrospective observational cohort of 153 consecutive children post-HCT requiring NIPPV from 2010-2016., Results: 97 (63%) failed NIPPV. Factors associated with failure on univariate analysis included: longer oxygen use prior to NIPPV (p=0.04), vasoactive agent use (p<0.001), and higher respiratory rate at multiple hours of NIPPV use (1hr p=0.02, 2hr p=0.04, 4hr p=0.008, 8hr p=0.002). Using respiratory rate at 4 hours a multivariable model was constructed. This model demonstrated high ability to discriminate NIPPV failure (AUC=0.794) with the following results: respiratory rate >40 at 4 hours [aOR=6.3 9(95% CI: 2.4, 16.4), p<0.001] and vasoactive use [aOR=4.9 (95% CI: 1.9, 13.1), p=0.001]. Of note, 11 patients had a cardiac arrest during intubation (11%) and 3 others arrested prior to intubation. These 14 patients were closer to HCT [14 days (IQR:4, 73) vs 54 (IQR:21,117), p<0.01] and there was a trend toward beginning NIPPV outside of the PICU and arrest during/prior to intubation (p=0.056)., Conclusions: In this cohort respiratory rate at 4 hours and vasoactive use are independent risk factors of NIPPV failure. An objective model to predict which children may benefit from a trial of NIPPV, may also inform the timing of both NIPPV initiation and uncomplicated intubation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Rowan, Fitzgerald, Agulnik, Zinter, Sharron, Slaven, Kreml, Bajwa, Mahadeo, Moffet, Tarquinio and Steiner.)

Introduction: The lung clearance index (LCI) derived from the multiple breath washout test (MBW), is both feasible and sensitive to early lung disease detection in young children with cystic fibrosis and asthma. The utility of LCI has not been studied in children with sickle cell disease (SCD). We hypothesized that children with SCD, with or without asthma or airway hyperreactivity (AHR), would have an elevated LCI compared to healthy controls., Methods: Children with SCD from a single center between the ages of 6 and 18 years were studied at baseline health and completed MBW, spirometry, plethysmography and blood was drawn for serum markers. Results were compared to healthy controls of similar race, age, and gender., Results: Healthy controls (n = 35) had a significantly higher daytime oxygen saturation level, weight and body mass index but not height compared to participants with SCD (n = 34). Total lung capacity (TLC) z-scores were significantly higher in the healthy controls compared to those with SCD (0.87 [1.13] vs. 0.02 [1.27]; p = .005) while differences in forced expiratory volume in 1 s z-scores approached significance (0.26 [0.97] vs. -0.22 [1.09]; p = .055). There was no significant difference in LCI between the healthy controls compared to participants with SCD (7.29 [0.72] vs. 7.40 [0.69]; p = .514)., Conclusion: LCI did not differentiate SCD from healthy controls in children between the ages of 6 and 18 years at baseline health. TLC may be an important pulmonary function measure to follow longitudinally in the pediatric SCD population., (© 2020 Wiley Periodicals LLC.)

Objective: The primary objective was to evaluate the efficacy of a weekly palliative care-guided, case-based discussion of high-risk infants on Neonatal Intensive Care Unit (NICU) physician (MD) and Advanced Practice Provider (APP) perceptions of pediatric palliative care (PPC). Study Design: The study setting was a level IV academic NICU in a United States midwestern children's hospital. A pre/post design was used to evaluate the effects of a weekly palliative care-guided, case-based discussion of high-risk infants on neonatology providers' (MD and APP) perspectives of palliative and end-of-life care in the NICU using a previously published survey instrument. Surveys were completed at baseline and after 12 months of implementation. Data was analyzed with a Wilcoxon Signed Rank test with significance set at p  < 0.05. Results: Thirty-one providers (13 APPs and 18 MDs) completed both pre- and post-intervention surveys. Post-intervention, providers were more likely to endorse that they "are comfortable with PPC", "feel comfortable teaching PPC to trainees", "feel confident handling end-of-life care", "have time to discuss PPC", and "were satisfied with the transition to end-of-life care for their most recent patient". They also were more likely to report, "families' perception of burden is relevant when making ethical decisions", that "parents are involved in decisions regarding palliative care", and that their "institution is supportive of palliative care." ( p -values < 0.05 for all). Conclusion: NICU provider perceptions of palliative care can be improved through the implementation of a case-based interdisciplinary conference that emphasizes palliative care domains in the context of Neonatal ICU care., Competing Interests: No competing financial interests exist., (© Jayme D. Allen et al., 2021; Published by Mary Ann Liebert, Inc.)

Background: High-flow nasal cannula (HFNC) therapy is a respiratory modality that has been adopted to support pediatric patients with bronchiolitis. There is no standardized protocol for initiation, escalation, or weaning of HFNC in the pediatric ICU. The aim of this respiratory therapist (RT)-driven quality improvement management protocol was to decrease duration of HFNC., Methods: An RT-driven HFNC management protocol based on an objective respiratory score was implemented in 2017 at a quaternary care children's hospital. Subjects included children less than 2 y old admitted to the pediatric ICU with bronchiolitis. All subjects needing HFNC were scored and placed within the protocol as appropriate for age, then weaned or escalated per the scoring tool. Comparison to a pre-intervention control group was performed. Average HFNC duration per subject was used as the primary outcome measure. Protocol compliance was used as a process measure. Noninvasive ventilation use, intubation rate, and 30-d pediatric ICU readmission rate were used as balancing measures. RT satisfaction with HFNC management before and after protocol implementation were measured., Results: Protocol compliance was sustainable and above the goal of 80% after 4 months of protocol implementation. HFNC duration decreased from 2.5 d to 2 days for each subject during planning and then to 1.8 d after protocol implementation. Length of stay (LOS) in the pediatric ICU and hospital LOS decreased from 2.6 d to 2.1 d and from 5.7 d to 4.7 d after protocol implementation, respectively. The use of noninvasive ventilation and the rate of intubation did not change significantly. RTs reported increased involvement in HFNC management decisions and appropriateness on how quickly the team weaned HFNC., Conclusions: An RT-driven HFNC management protocol was safely implemented in a pediatric ICU and decreased HFNC duration, pediatric ICU LOS, and hospital LOS. It allows the RT to work independently to the highest extent of their scope of practice, leading to improvement in RT job satisfaction., Competing Interests: The authors have disclosed no conflicts of interest., (Copyright © 2021 by Daedalus Enterprises.)

Background: Invasive mechanical ventilation is a lifesaving intervention that is associated with short- and long-term morbidities. Extubation readiness protocols aim to decrease extubation failure rates and simultaneously shorten the duration of invasive ventilation. This study sought to analyze extubation readiness practices at one institution and identify barriers to extubation in pediatric patients who have passed an extubation readiness test (ERT)., Methods: We performed a retrospective chart review of all pediatric subjects admitted between April 2017 and March 2018, and who were on mechanical ventilation. Exclusion criteria were cardiac ICU admission, tracheostomy, chronic ventilator support, limited resuscitation status, and death before extubation attempt. Data with regard to the method of ERT and reasons for delaying extubation were collected., Results: There were 427 subjects included in the analysis with 69% having had an ERT before extubation. Of those, 39% were extubated per our daily spontaneous breathing trial (SBT) protocol, and the daily SBT failed in 30% but they had passed a subsequent pressure support and CPAP trial on the same day. The most common reasons for failing the daily SBT were a lack of spontaneous breathing (30% [75/252]), being intubated < 24 h (24% [60/252]), breathing frequency outside the target range (22% [55/252]), and not meeting tidal volume goal (14% [34/252]). The most common documented reasons for delaying extubation despite passing daily SBT were planned procedure (29% [26/90]), neurologic status (23% [21/90]), and no leak around the endotracheal tube (18% [16/90]). The median time between passing ERT and extubation was 7 h (interquartile range, 5-10)., Conclusions: In our institution, there was variation in extubation readiness practices that could lead to a significant delay in liberation from invasive ventilation. Adjustment of our daily SBT to tolerate a higher work of breathing, such as higher breathing frequencies and lower tidal volumes, and incorporating sedation scoring into the protocol could be made without significantly affecting extubation failure rates., (Copyright © 2021 by Daedalus Enterprises.)

Background and Aims: Traditional laboratory markers are insensitive in distinguishing between patients with acute liver failure (ALF) who will require urgent liver transplantation (LT) from those who will recover spontaneously, particularly within 24 h of presentation. Coagulation factor-V (FV) may improve the accuracy of outcome prediction in ALF due to its predominant synthesis in the liver and short half-life in plasma., Methods: Patients enrolled in the ALF Study Group Registry from a single site had FV determined within 24 h of presentation (Derivation-Cohort). Area under the receiver operating characteristic curves (AUROC) dichotomized by ALF etiology [acetaminophen (APAP) or non-APAP] were constructed to evaluate the diagnostic performance of FV for transplant-free-survival (TFS). Multivariate logistic regression modeling was performed using FV and other clinical variables to predict TFS. Accuracy of FV and multivariable model were performed in a Validation-Cohort from a different site., Results: 90-patients (56% with APAP) were included in the Derivation-Cohort. Median FV was significantly higher in TFS versus those who died/LT (31% vs. 15%, respectively; p = 0.001). When dichotomized by etiology, AUROC for FV was 0.77 for APAP (cutoff, sensitivity, specificity 10.5%, 79%, 69%, respectively) and 0.77 for non-APAP (22%, 85%, 67%, respectively). When the optimal cutoffs for FV in the Derivation-Cohort were applied to the Validation-Cohort (N = 51; 59% with APAP), AUROC for FV was 0.75 for APAP (sensitivity/specificity 81/44) and 0.95 for non-APAP (sensitivity/specificity 90/73). In multivariate analyses, AUROC for FV model was 0.86 in the Derivation-Cohort and 0.90 in the Validation-Cohort., Conclusion: Admission FV may improve selection of patients who are likely to improve without LT.

Children admitted to the pediatric intensive care unit (PICU) often require multiple medications to achieve comfort and sedation. Although starting doses are available, these medications are typically titrated to the desired effect. Both oversedation and undersedation are associated with adverse events. The aim of this retrospective study was to evaluate cumulative medication burden necessary to achieve comfort in patients in the PICU and determine relevant predictors of medication needs. In order to account for all of the sedative medications, z-scores were used to assess the population average dose of each medication and compare each patient day to this population average. Sedation regimens for 130 patients in the PICU were evaluated. Mean overall infusion rates of fentanyl, morphine, and hydromorphone were 1.67 ± 0.81 µg/kg/hour, 0.12 ± 0.08 mg/kg/hour, and 17.84 ± 13.4 µg/kg/hour, respectively. The mean infusion rate of dexmedetomidine was 0.59 ± 0.28 µg/kg/hour, and midazolam was 0.14 ± 0.1 mg/kg/hour. Summation z-sores were used to rank the amount of sedation medication needed to achieve comfort for each individual patient for his/her PICU stay in relation to the entire sample. Patient age, weight, and length of mechanical ventilation were all significant predictors of sedation requirement. This study will provide data necessary to develop a model of cumulative medication burden needed to achieve appropriate sedation in this population. This descriptive model in appropriately ranking patients based on sedative needs is the first step in exploring potential genetic factors that may provide an insight into homing in on the appropriate sedation regimen., (© 2020 The Authors. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of the American Society for Clinical Pharmacology and Therapeutics.)

Background: We aimed to conduct a multi-centre study characterising emergency department utilisation and critical readmissions experienced by children with Fontan circulation., Methods: We conducted a retrospective review of children who underwent the Fontan operation at three institutions (i.e., centres A, B, and C) between 2009 and 2014, with follow-up through December 2015. Multi-variable analyses were performed to determine factors associated for emergency department utilisation within 1 year of surgery, emergency department utilisation at any time following surgery, or critical readmission (defined as admission to ICU, operating room, or cardiac catheterisation)., Results: We reviewed 297 patients, of which 147 patients (49%) had 607 emergency department encounters. Forty-six patients (15%) required 71 critical readmissions. Multi-variable analyses revealed centre C (p = 0.02) and post-operative hospitalisation ≥ 14 days (p = 0.03) to be significantly associated with emergency department utilisation within 1 year, whereas centre B (p < 0.001), post-operative hospitalisation ≥ 14 days (p = 0.002), and African-American/Black race (p = 0.04) were significantly associated with critical readmission., Conclusions: In this multi-centre study, nearly half of patients with Fontan circulation received emergency department care, often presenting with high disease acuity requiring readmission. Emergency department utilisation and need for critical readmission were independently influenced by the centre at which surgery was performed, prolonged post-operative hospitalisation, and racial background. These data could help guide quality improvement efforts aimed at reducing morbidity in this unique patient population.

Objectives: High-flow nasal cannula and noninvasive positive pressure ventilation have become ubiquitous in contemporary PICUs. Practice patterns associated with the use of these modalities have not been well described. In this study, we aimed to describe the use of high-flow nasal cannula and noninvasive positive pressure ventilation in children after extubation and analyze the progression of usage in association with patient factors. Our secondary aim was to describe interventions used for postextubation stridor., Design: Single-center retrospective cohort study., Setting: A 36-bed quaternary medical-surgical PICU., Patients: Mechanically ventilated pediatric patients admitted between April 2017 and March 2018. Exclusions were patients in the cardiac ICU, patients requiring a tracheostomy or chronic ventilatory support, and patients with limited resuscitation status., Interventions: None., Measurements and Main Results: Data regarding respiratory modality use was collected for the first 72 hours after extubation. There were 427 patients included in the analysis; 51 patients (11.9%) were extubated to room air, 221 (51.8%) to nasal cannula, 132 (30.9%) to high-flow nasal cannula, and 23 (5.4%) to noninvasive positive pressure ventilation. By 72 hours, 314 patients (73.5%) were on room air, 52 (12.2%) on nasal cannula, 29 (6.8%) on high-flow nasal cannula, eight (1.9%) on noninvasive positive pressure ventilation, and 24 (5.6%) were reintubated. High-flow nasal cannula was the most used respiratory modality for postextubation stridor. Multivariate analysis demonstrated that longer duration of invasive mechanical ventilation increased the odds of initial high-flow nasal cannula and noninvasive positive pressure ventilation use, and a diagnosis of cerebral palsy increased the odds of escalating from high-flow nasal cannula to noninvasive positive pressure ventilation in the first 24 hours post extubation., Conclusions: High-flow nasal cannula is commonly used immediately after pediatric extubation and the development of postextubation stridor; however, its usage sharply declines over the following 72 hours. Larger multicenter trials are needed to identify high-risk patients for extubation failure that might benefit the most from prophylactic use of high-flow nasal cannula and noninvasive positive pressure ventilation after extubation.

Introduction: Obstructive sleep apnea (OSA) in young children is caused by upper airway obstruction and is associated with changes in cognitive development, temperament and behavior. Adenotonsillectomy (AT) is often utilized as first line therapy for pediatric OSA. Children with laryngomalacia (LM) have a high chance of residual OSA after AT. There is paucity of literature regarding surgically naïve young children with OSA and laryngomalacia. Our study aimed to compare demographics, comorbidities and outcomes associated with OSA in surgically naïve young children with and without laryngomalacia., Methods: Retrospective chart review of surgically naïve young children (<2-year-old) with polysomnogram (PSG) diagnosed OSA. All young children underwent pre-operative PSG followed by drug-induced sleep endoscopy (DISE) directed intervention. Variables documented included demographics, comorbidities, history of adenotonsillectomy, DISE directed surgical interventions and pre and post PSG findings. Laryngomalacia was defined as presence of obstruction (Chan Parikh score ≥ 2) at the supraglottic level on DISE evaluation. Demographics and prevalence of comorbidities of those with and without LM were compared using t-test (continuous) and Chi Square (categorical). P value is significant for <0.05., Results: 79 surgically naïve young children with PSG diagnosed OSA performed between 2015 and 2019 were included in the study. Children with LM were younger in age (11 months) and had a higher OSA-18 score (35) compared to children without LM (17 months) (OSA-18 score: 5). No significant difference was noted in the pre-DISE PSG parameters in the 2 groups. 56.1% of children with OSA and laryngomalacia did not need AT. Both children with and without laryngomalacia showed improvement in AHI on post-DISE PSG. Higher baseline AHI was associated with greater improvement in AHI., Conclusion: Surgically naïve young children with OSA and LM present earlier than those without LM and report a significantly worse quality of life Young children with a higher baseline AHI were found to have greater improvement in severity of OSA post-DISE and surgical intervention. Majority of children with OSA and laryngomalacia did not need adenotonsillectomy after a preprocedural DISE assessment yet showed similar improvement in AHI. More studies are needed to determine which patients with OSA and laryngomalacia will need multilevel interventions., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Truncal valve management in patients with truncus arteriosus is a clinical challenge, and indications for truncal valve intervention have not been defined. We sought to evaluate truncal valve dysfunction and primary valve intervention in patients with truncus arteriosus and determine risk factors for later truncal valve intervention. We conducted a retrospective cohort study of children who underwent truncus arteriosus repair at 15 centers between 2009 and 2016. Multivariable competing risk analysis was performed to determine risk factors for later truncal valve intervention. We reviewed 252 patients. Forty-two patients (17%) underwent truncal valve intervention during their initial surgery. Postoperative extracorporeal support, CPR, and operative mortality for patients who underwent truncal valve interventions were statistically similar to the rest of the cohort. Truncal valve interventions were performed in 5 of 64 patients with mild insufficiency; 5 of 16 patients with mild-to-moderate insufficiency; 17 of 35 patients with moderate insufficiency; 5 of 9 patients with moderate-to-severe insufficiency; and all 10 patients with severe insufficiency. Twenty patients (8%) underwent later truncal valve intervention, five of whom had no truncal valve intervention during initial surgical repair. Multivariable analysis revealed truncal valve intervention during initial repair (HR 11.5; 95% CI 2.5, 53.2) and moderate or greater truncal insufficiency prior to initial repair (HR 4.0; 95% CI 1.1, 14.5) to be independently associated with later truncal valve intervention. In conclusion, in a multicenter cohort of children with truncus arteriosus, 17% had truncal valve intervention during initial surgical repair. For patients in whom variable truncal valve insufficiency is present and primary intervention was not performed, late interventions were uncommon. Conservative surgical approach to truncal valve management may be justifiable.

Antenatal corticosteroids (ACS) administration to pregnant women for threatened preterm labor is standard obstetric care to reduce neonatal respiratory distress syndrome and the associated respiratory morbidity. While ACS stimulates surfactant production in the fetal lung, the effects of ACS upon the subsequent growth and development of the lung are unclear. Follow-up studies outside of the neonatal period have been primarily limited to spirometry, and most subjects evaluated were born prematurely. To our knowledge, no study has assessed both airway and parenchymal function in infants or adults following ACS exposure. We hypothesized that ACS impairs lung growth and performed infant pulmonary function testing, which included spirometry, alveolar volume (V A ) and lung diffusion (D L ). As a pilot study, we limited our assessment to infants whose mothers received ACS for threatened preterm labor, but then proceeded to full term delivery. This approach evaluated a more homogenous population and eliminated the confounding effects of preterm birth. We evaluated 36 full-term infants between 4 to 12 months of age; 17 infants had ACS exposure and 19 infants had no ACS exposure. Infants exposed to ACS had a significantly lower forced vital capacity compared with non-ACS exposed infants (250 vs 313 mL; P = .0075). FEV 0.5 tended to be lower for the ACS exposed group (205 vs 237 mL; P = .075). V A and D L did not differ between the two groups. These findings suggest that ACS may impair subsequent growth of the lung parenchyma., (© 2020 Wiley Periodicals LLC.)

Mechanisms driving adaptive developmental responses to chronic high-altitude (HA) exposure are incompletely known. We developed a novel rat model mimicking the human condition of cardiopulmonary adaptation to HA starting at conception and spanning the in utero and postnatal timeframe. We assessed lung growth and cardiopulmonary structure and function and performed transcriptome analyses to identify mechanisms facilitating developmental adaptations to chronic hypoxia. To generate the model, breeding pairs of Sprague-Dawley rats were exposed to hypobaric hypoxia (equivalent to 9,000 ft elevation). Mating, pregnancy, and delivery occurred in hypoxic conditions. Six weeks postpartum, structural and functional data were collected in the offspring. RNA-Seq was performed on right ventricle (RV) and lung tissue. Age-matched breeding pairs and offspring under room air (RA) conditions served as controls. Hypoxic rats exhibited significantly lower body weights and higher hematocrit levels, alveolar volumes, pulmonary diffusion capacities, RV mass, and RV systolic pressure, as well as increased pulmonary artery remodeling. RNA-Seq analyses revealed multiple differentially expressed genes in lungs and RVs from hypoxic rats. Although there was considerable similarity between hypoxic lungs and RVs compared with RA controls, several upstream regulators unique to lung or RV were identified. We noted a pattern of immune downregulation and regulation patterns of immune and hormonal mediators similar to the genome from patients with pulmonary arterial hypertension. In summary, we developed a novel murine model of chronic hypoxia exposure that demonstrates functional and structural phenotypes similar to human adaptation. We identified transcriptomic alterations that suggest potential mechanisms for adaptation to chronic HA.

Background: Depression is associated with an increased risk of cardiovascular disease in human immunodeficiency virus (HIV). We hypothesized that reducing depressive symptoms would improve HIV-related cardiovascular risk., Methods: We conducted a single-center, randomized (1:1), controlled, parallel-group, assessor-blinded, pilot trial comparing Beating the Blues US (BtB)-an evidence-based, 8-session, internet cognitive-behavioral therapy for depression-with usual care (UC) in HIV-positive participants receiving virologically suppressive antiretroviral therapy and with Patient Health Questionnaire (PHQ)-9 scores ≥10. The primary endpoint was change in brachial artery flow-mediated dilation (FMD) at 12 weeks. Secondary endpoints were FMD change at 24 weeks and inflammation, coagulation, and metabolic biomarker changes at 12 and 24 weeks., Results: Fifty-four participants were randomized (27 in each arm). Mean reductions in PHQ-9 scores were significantly greater with BtB versus UC at 12 weeks (-5.60 vs -1.52; P  = .007) and 24 weeks (-6.00 vs -1.38; P  = .008); reductions in the Hopkins Symptom Checklist Depression Scale-20 scores were also significantly greater with BtB versus UC at 24 weeks (-0.72 vs -0.35; P  = .029). Changes in FMD between arms were not significantly different at 12 or 24 weeks. Significantly larger reductions in soluble (s)CD14 and sCD163 with BtB versus UC were found at 12 and 24 weeks, respectively., Conclusions: Compared with UC, internet cognitive-behavioral therapy using BtB resulted in greater improvements in depressive symptoms and monocyte activation markers but did not improve FMD in this pilot trial. These data support performing larger studies to determine the potential salutatory effects of behavioral therapies for depression on HIV-related inflammation., (© The Author(s) 2020. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Many children with inflammatory bowel disease (IBD) are taking immunosuppressant medications that place them at risk for vaccine preventable diseases. Despite national guidelines, children with IBD have low vaccination rates. Adult data suggest that there is concern about the safety of vaccines. There are no current studies addressing perceived safety about vaccinations among families of children with IBD., Methods: A total of 108 caregivers of children (ages 10-25 years) were surveyed during their outpatient visit, with approximately half having a diagnosis of IBD. The survey consisted of validated questions regarding vaccine safety and opinions. After enrollment, state-wide vaccine registry data was collected. Demographics between the two groups were compared using Ch-square and the Wilcoxon rank-sum tests to analyze Likert scale questions., Results: The majority of children followed for IBD were Caucasian males, had Crohn's disease (68%) and were immunosuppressed. Results from the survey revealed a concern about vaccine safety (40% vs. 16%, p=0.03) and overall effectiveness (34% vs. 12%, p<0.01) in the IBD group compared to the non-IBD. Furthermore, more IBD families were worried that vaccines would worsen their child's symptoms (36% vs. 10%, p=<0.01). The majority of children were missing the flu and/or HPV vaccine. Finally, 96% of the children on a biologic for their IBD were missing the PPSV23 booster., Conclusions: Caregivers of children with IBD are more concerned about vaccine safety and effectiveness than those with non-IBD diagnosis. Despite being on immunosuppressant medications, many patients were missing recommended vaccines.

Objective: Understanding lung cancer screening behaviour is crucial to identifying potentially modifiable factors for future intervention. Qualititative work has explored attitudes and beliefs about lung cancer screening from the perspective of the participant, but the theoretically grounded factors that influence screening-eligible individuals to screen are unknown. We tested an explanatory framework for lung cancer screening participation from the individual's perspective., Methods: Data were collected as part of a sequential explanatory mixed methods study, the quantitative component of which is reported here. A national purposive sample of 515 screening-eligible participants in the United States was recruited using Facebook-targeted advertisement. Participants completed surveys assessing constructs of the Conceptual Model for Lung Cancer Screening Participation. Path analysis was used to assess the relationships between variables., Results: Path analyses revealed that a clinician recommendation to screen, higher self-efficacy scores, and lower mistrust scores were directly associated with screening participation (p < 0.05). However, the link between screening behaviour and self-efficacy appeared to be fully mediated by fatalism, lung cancer fear, lung cancer family history, knowledge of lung cancer risk and screening, income, clinician recommendation, and social influence (p < 0.05)., Conclusions: This study found that medical mistrust, self-efficacy, and clinician recommendation were significant in the decision of whether to screen for lung cancer. These findings offer insight into potentially modifiable targets most appropriate on which to intervene. This understanding is critical to design meaningful clinician- and patient-focused interventions.

Importance: An important aspect of high-quality care is ensuring that treatments are in alignment with patient or surrogate decision-maker goals. Treatment discordant with patient goals has been shown to increase medical costs and prolong end-of-life difficulties., Objectives: To evaluate discordance between surrogate decision-maker goals of care and medical orders and treatments provided to hospitalized, incapacitated older patients., Design, Setting, and Participants: This prospective cohort study included 363 patient-surrogate dyads. Patients were 65 years or older and faced at least 1 major medical decision in the medical and medical intensive care unit services in 3 tertiary care hospitals in an urban Midwestern area. Data were collected from April 27, 2012, through July 10, 2015, and analyzed from October 5, 2018, to December 5, 2019., Main Outcomes and Measures: Each surrogate's preferred goal of care was determined via interview during initial hospitalization and 6 to 8 weeks after discharge. Surrogates were asked to select the goal of care for the patient from 3 options: comfort-focused care, life-sustaining treatment, or an intermediate option. To assess discordance, the preferred goal of care as determined by the surrogate was compared with data from medical record review outlining the medical treatment received during the target hospitalization., Results: A total of 363 dyads consisting of patients (223 women [61.4%]; mean [SD] age, 81.8 [8.3] years) and their surrogates (257 women [70.8%]; mean [SD] age, 58.3 [11.2] years) were included in the analysis. One hundred sixty-nine patients (46.6%) received at least 1 medical treatment discordant from their surrogate's identified goals of care. The most common type of discordance involved full-code orders for patients with a goal of comfort (n = 41) or an intermediate option (n = 93). More frequent in-person contact between surrogate and patient (adjusted odds ratio [AOR], 0.43; 95% CI, 0.23-0.82), patient residence in an institution (AOR, 0.44; 95% CI, 0.23-0.82), and surrogate-rated quality of communication (AOR, 0.98; 95% CI, 0.96-0.99) were associated with lower discordance. Surrogate marital status (AOR for single vs married, 1.92; 95% CI, 1.01-3.66), number of family members involved in decisions (AOR for ≥2 vs 0-1, 1.84; 95% CI, 1.05-3.21), and religious affiliation (AOR for none vs any, 4.87; 95% CI, 1.12-21.09) were associated with higher discordance., Conclusions and Relevance: This study found that discordance between surrogate goals of care and medical treatments for hospitalized, incapacitated patients was common. Communication quality is a modifiable factor associated with discordance that may be an avenue for future interventions.

Background: When working with surrogate decision-makers, physicians often encounter ethical challenges that may cause moral distress which can have negative consequences for physicians., Objective: To determine frequency of and factors associated with physicians' moral distress caring for patients requiring a surrogate., Design: Prospective survey., Participants: Physicians (n = 154) caring for patients aged 65 years and older and their surrogate decision-makers (n = 362 patient/surrogate dyads). Patients were admitted to medicine or medical intensive care services, lacked decisional capacity and had an identified surrogate., Main Measures: Moral distress thermometer., Key Results: Physicians experienced moral distress in the care of 152 of 362 patients (42.0%). In analyses adjusted for physician, patient, and surrogate characteristics, physician/surrogate discordance in preferences for the plan of care was not significantly associated with moral distress. Physicians were more likely to experience moral distress when caring for older patients (1.06, 1.02-1.10), and facing a decision about life-sustaining treatment (3.58, 1.54-8.32). Physicians were less likely to experience moral distress when caring for patients residing in a nursing home (0.40, 0.23-0.69), patients who previously discussed care preferences (0.56, 0.35-0.90), and higher surrogate ratings of emotional support from clinicians (0.94, 0.89-0.99). Physicians' internal discordance when they prefer a more comfort-focused plan than the patient is receiving was associated with significantly higher moral distress (2.22, 1.33-3.70) after adjusting for patient, surrogate, and physician characteristics., Conclusions: Physician moral distress occurs more frequently when the physician is male, the patient is older or requires decisions about life-sustaining treatments. These findings may help target interventions to support physicians. Prior discussions about patient wishes is associated with lower distress and may be a target for patient-centered interventions.

Background: Patients with Alzheimer's disease and related dementias (ADRD) and traumatic brain injury (TBI) and their caregivers require cognitive and behavioral symptom management, interdisciplinary care, support for caregivers, and seamless care coordination between providers. Caring for someone with ADRD or TBI is associated with higher rates of psychological morbidity and burden, social isolation, financial hardship, and deterioration of physical health. Tremendous need exists for primary care-based interventions that concurrently address the care needs of dyads and aim to improve care and outcomes for both individuals with ADRD and TBI and their family caregivers., Methods: The Aging Brain Care Acquiring New Skills While Enhancing Remaining Strengths (ABC ANSWERS) study is a randomized controlled trial that tests the effectiveness of an intervention based on two evidence-based programs that have been developed for and previously tested in populations with ADRD, TBI, stroke, and late-life depression and/or who have survived an intensive care unit stay. This study includes 200 dyads comprised of a veteran with a diagnosis of ADRD or TBI and the veteran's primary informal caregiver. Dyads are randomized to receive the ABC ANSWERS intervention or routine Veterans Health Administration (VHA) primary care with a standardized educational and resource information packet. Data collection occurs at baseline and three follow-up time points (3 months, 6 months, and 12 months). The primary outcome is caregiver quality of life (QoL). A secondary measure for the caregiver is caregiver burden. Secondary measures for both the veteran and caregiver include symptoms of depression and anxiety., Discussion: The ABC ANSWERS intervention integrates common features of an evidence-based collaborative care model for brain health while concurrently attending to the implementation barriers of delivering care and skills to dyads. We hypothesize that caregivers in dyads randomized to the ABC ANSWERS program will experience higher levels of QoL and lower levels of depression, anxiety, dyadic strain, and caregiver burden at 12 months than those receiving usual VHA primary care., Trial Registration: ClinicalTrials.gov, NCT03397667. Registered on 12 January 2018.

Objective: To correlate the clinical severity of laryngomalacia (LM) with endoscopic findings, swallowing evaluations and polysomnography in a cohort of patients. Method: We conducted a retrospective analysis between 2017-2018 on a cohort of patients diagnosed with upper airway obstruction (UAO), stridor, noisy breathing or laryngomalacia. This study took place at the Pediatric Pulmonology Department, Riley Children's Hospital, Indianapolis, United States of America., Results:   There were 157 patients with laryngomalacia included in the study. Patients with severe LM were significantly younger than those with mild LM (p=0.0214) and moderate LM (p=0.0220). Subjects with type I of LM were significantly older than type III (p=0.0051). When associations were tested between polysomnogram (PSG) variables and clinical severity, there were significant associations with age at PSG. The overall apnea-hypopnea index (AHI) in mild (p=0.0103) and moderate (p=0.0242) were significantly lower than the severe group. The rapid eye movement (REM) AHI was significantly lower in moderate cases than severe (p=0.0134). The end-tidal carbon dioxide (EtCO2) peak was significantly lower in mild cases than severe (p=0.0141). The total sleep time (TST) peripheral capillary oxygen saturation (SpO2) 90% occurs in both mild (p=0.0197) and moderate (p=0.0498) were significantly lower than the severe group., Conclusions: The severity of the clinical manifestations of LM did not correlate with the different endoscopic types in our study. The presence of cyanosis was associated with type III LM. Rapid eye movement AHI and EtCO2 in polysomnogram were remained significantly associated with clinical severity.

Exposure to high-dose total body irradiation (TBI) can result in hematopoietic acute radiation syndrome (H-ARS), characterized by leukopenia, anemia, and coagulopathy. Death from H-ARS occurs from hematopoietic insufficiency and opportunistic infections. Following radiation exposure, red blood cells (RBCs) undergo hemolysis from radiation-induced hemoglobin denaturation, causing the release of iron. Free iron can have multiple detrimental biological effects, including suppression of hematopoiesis. We investigated the impact of radiation-induced iron release on the bone marrow following TBI and the potential impact of the ACE inhibitor captopril, which improves survival from H-ARS. C57BL/6J mice were exposed to 7.9 Gy, 60 Co irradiation, 0.6 Gy/min (LD 70-90/30 ). RBCs and reticulocytes were significantly reduced within 7 days of TBI, with the RBC nadir at 14-21 days. Iron accumulation in the bone marrow correlated with the time course of RBC hemolysis, with an ∼10-fold increase in bone marrow iron at 14-21 days post-irradiation, primarily within the cytoplasm of macrophages. Iron accumulation in the bone marrow was associated with increased expression of genes for iron binding and transport proteins, including transferrin, transferrin receptor 1, ferroportin, and integrin αMβ2. Expression of the gene encoding Nrf2, a transcription factor activated by oxidative stress, also increased at 21 days post-irradiation. Captopril did not alter iron accumulation in the bone marrow or expression of iron storage genes, but did suppress Nrf2 expression. Our study suggests that following TBI, iron is deposited in tissues not normally associated with iron storage, which may be a secondary mechanism of radiation-induced tissue injury., Competing Interests: Conflict of interest disclosure All authors confirm that there are no financial or nonfinancial conflicts of interest., (Published by Elsevier Inc.)

Extracorporeal membrane oxygenation (ECMO) is a low-volume, high-risk modality of care. Clinical specialists (CS) who manage ECMO circuit emergencies vary in background and approach to circuit emergencies based on institutional training standards, leading to variation that may impact the quality of care. Validated checklists to assess CS performance are crucial to eliminate disparities and improve efficiency. This study focused on the development and validation of checklists to evaluate the clinical performance of ECMO CS in three ECMO circuit emergencies. A research team with diverse clinical background from our institution developed the first iteration of three ECMO emergency checklists: (1) venous air, (2) arterial air, and (3) oxygenator failure. A modified Delphi technique with a panel of 11 national content experts in ECMO was used to develop content validity evidence. Rating scales from 1 to 7 were used to evaluate each checklist item. The response rate for three rounds of Delphi was 100%. Items with mean score >4 were kept, and new item recommendations were added based on comments from the panel. The venous air, arterial air, and oxygenator failure checklists were revised from 10, 13, and 9 items to 12, 12, and 10 items, respectively. A Cronbach's α of 0.74 during the second round of responses indicated an acceptable degree of agreement. This study demonstrated content validation of three ECMO emergency checklists to assess performance of ECMO CS using a consensus-based Delphi technique. Future validity evidence should be acquired by implementing these checklists in the simulation environments.

Background: Kidney transplant (KT) recipients have higher incidence of malignancies, including Human Papillomavirus (HPV)-associated cancers. Thus, HPV vaccines may have an important role in preventing HPV-related disease in this population; however, immunogenicity and safety data are lacking. Objective: To examine the immunological response and tolerability to HPV vaccination in pediatric KT recipients compared to future KT candidates. Methods: The quadrivalent HPV vaccine was administered to girls and boys age 9-18 recruited from seven centers part of the Pediatric Nephrology Research Consortium. Subjects were recruited for three groups: (1) CKD: chronic kidney disease stages 3, 4, and 5 not on dialysis; (2) Dialysis; (3) KT recipients. The outcome consisted of antibody concentrations against HPV 6, 11, 16, and 18. Geometric mean titers (GMTs) and seroconversion rates were compared. Vaccine tolerability was assessed. Results: Sixty-five participants were recruited: 18 in the CKD, 18 in the dialysis, and 29 into the KT groups. KT patients had significantly lower GMTs after vaccination for all serotypes. The percentages of subjects who reached seroconversion were overall lower for the KT group, reaching statistical significance for HPV 6, 11, and 18. Comparing immunosuppressed subjects (anyone taking immunosuppression medications, whether KT recipient or not) with the non-immunosuppressed participants, the former had significantly lower GMTs for all the HPV serotypes and lower seroconversion rates for HPV 6, 11, and 18. KT females had higher GMTs and seroconversion rates for certain serotypes. There were no adverse events in either group. Conclusions: HPV vaccine was well-tolerated in this population. Pediatric KT recipients had in general lower GMTs and seroconversion rates compared to their peers with CKD or on dialysis. Immunosuppression played a role in the lack of seroconversion. Our results emphasize the importance of advocating for HPV vaccination prior to KT and acknowledge its safety post transplantation. Future studies are needed to investigate the effect of a supplemental dose of HPV vaccine in KT recipients who do not seroconvert and to evaluate the long-term persistence of antibodies post-KT., (Copyright © 2020 Nailescu, Nelson, Verghese, Twombley, Chishti, Mills, Mahan, Slaven and Shew.)

Context: Although religion and spirituality are important to surrogate decision makers, little is known about the role of religion in decision making regarding life-sustaining treatments., Objectives: To determine the relationships between dimensions of religion and spirituality and medical treatment decisions made by surrogates., Methods: This prospective observational study enrolled patient/surrogate dyads from three hospitals in one metropolitan area. Eligible patients were 65 years or older and admitted to the medicine or medical intensive care services. Baseline surveys between hospital days 2 and 10 assessed seven dimensions of religion and spirituality. Chart reviews of the electronic medical record and regional health information exchange six months after enrollment identified the use of life-sustaining treatments and hospice for patients who died., Results: There were 291 patient/surrogate dyads. When adjusting for other religious dimensions, demographic, and illness factors, only surrogates' belief in miracles was significantly associated with a lower surrogate preference for do-not-resuscitate status (adjusted odds ratio [aOR] 0.39; 95% CI 0.19, 0.78). Among patients who died, higher surrogate intrinsic religiosity was associated with lower patient receipt of life-sustaining treatments within the last 30 days (aOR 0.66; 95% CI 0.45, 0.97). Belief in miracles (aOR 0.30; 95% CI 0.10, 0.96) and higher intrinsic religiosity (aOR 0.70; 95% CI 0.53, 0.93) were associated with lower hospice utilization., Conclusion: Few religious variables are associated with end-of-life preferences or treatment. Belief in miracles and intrinsic religiosity may affect treatment and should be identified and explored with surrogates by trained chaplains or other clinicians with appropriate training., (Copyright © 2019 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: Buprenorphine (BUP) is commonly used for opioid maintenance therapy in pregnancy. Our goal was to determine whether liver dysfunction related to hepatitis C virus (HCV) infection impacts BUP dosing requirements in pregnancy., Study Design: This was a retrospective cohort study of pregnant women with antenatal exposure to BUP to compare dosing between individuals positive versus negative for HCV infection. Spearman correlation tests were used to assess the relationship between BUP dose and HCV status., Results: HCV infection was present in 103 (39%) of the patients. Patients with HCV infection required lower dose increases of BUP throughout pregnancy ( p  = 0.02). HCV viral load was positively correlated with the liver enzymes aspartate transaminase ( r  = 0.30, p  = 0.003) and alanine transaminase ( r  = 0.25, p  = 0.01). There was a negative correlation between HCV viral load and BUP dose during the second trimester ( r  = -0.27, p  = 0.01) and third trimester ( r  = -0.20, p  = 0.04)., Conclusion: Women with HCV infection required less of an increase in BUP dose throughout pregnancy compared with women without HCV infection. Severity of HCV infection, as measured by viral load and liver enzymes, was also associated with BUP dosing., Competing Interests: None declared., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Background: Late preterm infants (born 34-36 weeks gestation) without cystic fibrosis (CF) are at risk for growth failure during the first 2 years of life. Infants with CF are at risk of being born premature, and thus at risk for growth failure. The aim for this study was to assess weight-for-length (WFL) at 2 years of age for late preterm infants compared with term infants with CF., Methods: Data were collected from the US CF Foundation Patient Registry. We compared growth parameters between late preterm and term infants with CF born from 2010 to 2013. Our primary outcome was WFL <10 and <50 percentile at 2 years of age. A multivariate logistical regression analysis evaluated late preterm gestation and WFL<10 or <50 percentile., Results: A total of 2955 infants were born from 2010 to 2013 with CF. Eight percentage late preterm. Forty-five percentage late preterm versus 43% term were below the 50th percentile for WFL at age 2 years (P = 0.75). Twelve percentage late preterm versus 6% term for WFL <10 percentile at age 2 years (P = 0.010). The multivariate regression model identified 2-fold increased odds of being <10th percentile for WFL at age 2 years (P = 0.025) for preterm over term. Late preterm infants used higher calorie dense feeds and more feeding tubes (P = 0.035 and P = 0.006)., Conclusions: Late preterm infants with CF are at higher risk of being below the 10th percentile for WFL at 2 years of age compared with their term peers. This indicates a population that is at risk for growth failure.

Background & Aims: Mucosal exposure devices improve detection of lesions during colonoscopy and have reduced examination times in uncontrolled studies. We performed a randomized trial of Endocuff Vision vs standard colonoscopy to compare differences in withdrawal time (the primary end point). We proposed that Endocuff Vision would allow complete mucosal inspection in a shorter time without impairing lesion detection., Methods: Adults older than 40 years undergoing screening or surveillance colonoscopies were randomly assigned to the Endocuff group (n=101, 43.6% women) or the standard colonoscopy group (n=99; 57.6% women). One of 2 experienced endoscopists performed the colonoscopies, aiming for a thorough evaluation of the proximal sides of all haustral folds, flexures, and valves in the shortest time possible. Inspection time was measured with a stopwatch and calculated by subtracting washing, suctioning, polypectomy and biopsy times from total withdrawal time., Results: There were significantly fewer women in the Endocuff arm (P = .0475) but there were no other demographic differences between groups. Mean insertion time with Endocuff was 4.0 min vs 4.4 min for standard colonoscopy (P = .14). Mean inspection time with Endocuff was 6.5 min vs 8.4 min for standard colonoscopy (P < .0001). Numbers of adenomas detected per colonoscopy (1.43 vs 1.07; P = .07), adenoma detection rate (61.4% vs 52%; P = .21), number of sessile serrated polyps per colonoscopy (0.27 vs 0.21; P = .12), and sessile serrated polyp detection rate (19.8% vs 11.1%; P = .09) were all higher with Endocuff Vision. Results did not differ significantly when we controlled for age, sex, or race., Conclusion: In a randomized trial, we found inclusion of Endocuff in screening or surveillance colonoscopies to decrease examination time without reducing lesion detection. ClinicalTrials.gov, Number: NCT03361917., (Copyright © 2020 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Objective: Tracheostomy-dependent pediatric patients will often have respiratory cultures positive for Stenotrophomonas maltophilia (multidrug-resistant Gram-negative rod). There are limited data available to guide treatment in this population. The objective of this single-center, retrospective study was to evaluate if antibiotic treatment of S maltophilia improved clinical outcomes in tracheostomy-dependent pediatric patients., Methods: We included tracheostomy-dependent pediatric patients who had a respiratory culture positive for S maltophilia. Patients were divided into 2 groups: 1) treatment and 2) no treatment., Results: Forty patients with 55 encounters were included in this study. S maltophilia was treated with sulfamethoxazole-trimethoprim in 20 encounters (19 patients) and no antimicrobial treatment was given in 35 encounters (30 patients). The time to return to stable respiratory status was 5 days (0-10) (median [range]) in the treated group and 4 days (0-19) in the untreated group (p = 0.52). There was no statistically significant difference in time to baseline respiratory status between patients treated and those not treated for S maltophilia. There was no difference in hospital length of stay between patients who were or not treated., Conclusions: Based on these results, these data would suggest that there might not be a benefit to treating cultures positive for S maltophilia in tracheostomy-dependent pediatric patients., Competing Interests: Disclosure The authors declare no conflicts or financial interest in any product or service mentioned in the manuscript, including grants, equipment, medications, employment, gifts, and honoraria. The authors had full access to all the data and take responsibility for the integrity and accuracy of the data analysis., (Copyright Published by the Pediatric Pharmacy Association. All rights reserved. For permissions, email: mhelms@pediatricpharmacy.org 2019.)

Background: Viral infections contribute to morbidity in cystic fibrosis (CF), but the impact of respiratory viruses on the development of airway disease is poorly understood., Methods: Infants with CF identified by newborn screening were enrolled prior to 4 months of age to participate in a prospective observational study at 4 centers. Clinical data were collected at clinic visits and weekly phone calls. Multiplex PCR assays were performed on nasopharyngeal swabs to detect respiratory viruses during routine visits and when symptomatic. Participants underwent bronchoscopy with bronchoalveolar lavage (BAL) and a subset underwent pulmonary function testing. We present findings through 8.5 months of life., Results: Seventy infants were enrolled, mean age 3.1 ± 0.8 months. Rhinovirus was the most prevalent virus (66%), followed by parainfluenza (19%), and coronavirus (16%). Participants had a median of 1.5 viral positive swabs (range 0-10). Past viral infection was associated with elevated neutrophil concentrations and bacterial isolates in BAL fluid, including recovery of classic CF bacterial pathogens. When antibiotics were prescribed for respiratory-related indications, viruses were identified in 52% of those instances., Conclusions: Early viral infections were associated with greater neutrophilic inflammation and bacterial pathogens. Early viral infections appear to contribute to initiation of lower airway inflammation in infants with CF. Antibiotics were commonly prescribed in the setting of a viral infection. Future investigations examining longitudinal relationships between viral infections, airway microbiome, and antibiotic use will allow us to elucidate the interplay between these factors in young children with CF., (Copyright © 2019. Published by Elsevier B.V.)

In the Intensive Care Unit (ICU), family members experience psychological and spiritual distress as they cope with fear, grief, and medical decisions for patients. The study team developed and pilot tested a semistructured chaplain intervention that included proactive contact and spiritual assessment, interventions, and documentation. An interdisciplinary team developed the intervention, the Spiritual Care Assessment and Intervention (SCAI) Framework. Three chaplains delivered the intervention to surrogates in two ICUs. There were 25 of 73 eligible patient/surrogate dyads enrolled. Surrogates had a mean age of 57.6, were 84% female and 32% African American. The majority (84%) were Protestant. All received at least one chaplain visit and 19 received three visits. All agreed they felt supported by the chaplains, and qualitative comments showed spiritual and emotional support were valued. A semistructured spiritual care intervention for ICU surrogates is feasible and acceptable. Future work is needed to demonstrate the intervention improves outcomes for surrogates and patients.

Acute kidney injury (AKI) is a common complication in hospitalized patients with cirrhosis. Uromodulin, a protein uniquely produced by the kidney and released both in the urine and circulation, has been shown to regulate AKI and is linked to tubular reserve. Although low levels of urine uromodulin are associated with AKI after cardiac surgery, it is unclear whether circulating uromodulin can stratify the risk of AKI, particularly in a susceptible population such as hospitalized patients with cirrhosis. Thus, we investigated whether plasma uromodulin measured at the time of admission is associated with subsequent hospital-acquired AKI (defined by a rise in serum creatinine >0.3mg/dL within 48 h or ≥ 1.5 times baseline) in patients with cirrhosis. A total of 98 patients [mean age 54 yr, Model for Endstage Liver Disease Sodium (MELD-Na) score 19, and baseline creatinine of 0.95 mg/dL] were included, of which 13% ( n = 13) developed AKI. Median uromodulin levels were significantly lower in patients who developed AKI compared with patients who did not (9.30 vs. 13.35 ng/mL, P = 0.02). After adjusting for age, sex, diabetes, hypertension, albumin, and MELD-Na score as covariates on multivariable logistic regression, uromodulin was independently associated with AKI [odd ratios of 1.19 (95% confidence interval 1.02, 1.37; P = 0.02)]. Lower uromodulin levels on admission are associated with increased odds of subsequent AKI in hospitalized patients with cirrhosis. Further studies are needed to better understand the role of uromodulin in the pathogenesis and as a predictive biomarker of AKI in this population. NEW & NOTEWORTHY In this study, we found that admission plasma uromodulin levels are significantly lower in patients who developed subsequent acute kidney injury (AKI) during their hospital stay compared with patients who did not. Additionally, uromodulin is independently associated with AKI development after adjusting for clinically relevant parameters such as age, sex, diabetes, hypertension, severity of cirrhosis, and kidney function. To our knowledge, this is the first study linking plasma uromodulin with AKI development in patients with cirrhosis.

: Heightened systemic inflammation contributes to cardiovascular (CVD) events in people living with HIV (PLWH), although not all PLWH develop CVD, thus suggesting a genetic modifying role. We examined GCH1 polymorphisms, which have been associated with reduced endothelial function in European populations with CVD and increased inflammation, in a racially diverse cohort of US PLWH initiating antiretroviral therapy (ART). GCH1 polymorphisms differed by race and were not associated with flow-mediated dilation or carotid intima-media thickness before or after 48 weeks of ART.

Objectives: To investigate the effect of meal intake on liver stiffness measurement (LSM) and controlled attenuation parameter (CAP) in patients with biopsy-proven nonalcoholic fatty liver disease undergoing vibration-controlled transient elastography., Methods: LSM and CAP were assessed at baseline and serially for 6 hours after meal intake in 24 patients., Results: A significant increase in LSM was seen up to the 2-hour time point (26 ± 25%, P = 0.02). The CAP scores changed minimally with a maximal change of 3% (P > 0.1)., Conclusions: Three hours of fasting is necessary before evaluation with vibration-controlled transient elastography.

Introduction: There are few data on adherence and low-cost measurement tools for children living with HIV. We collected prospective data on adherence to antiretroviral therapy (ART) among a multinational cohort of children to evaluate an adherence questionnaire., Methods: We enrolled 319 children ages 0 to 16 years on ART in Kenya (n = 110), South Africa (n = 109) or Thailand (n = 100). Children were followed up for six months of adherence monitoring between March 2015 and August 2016 using Medication Event Monitoring Systems (MEMS ® ) with at least one viral load measure. At month 3 and 6, children or their caregivers were administered a 10-item adherence questionnaire. Repeated measures analyses were used to compare responses on questionnaire items to external adherence criteria: MEMS ® dichotomized adherence (≥90% of doses taken vs. <90%), 48-hour MEMS ® treatment interruptions and viral suppression (<1000 copies/mL). Items associated with outcomes (p < 0.10) were coefficient-weighted to calculate a total adherence score, which was tested in multivariate regression against MEMS ® and viral suppression outcomes. Odds ratios (OR) and 95% confidence intervals (95% CI) were calculated., Results: Mean child age was 11 years and 54% were female. Children from Thailand (median age 14 years) were significantly older compared to Kenya (10 years) and South Africa (10 years). Prevalence of viral suppression was 97% in Thailand, 81% in South Africa and 69% in Kenya, while the prevalence of MEMS ® adherence ≥90% was 57% in Thailand, 58% in South Africa and 40% in Kenya. Across sites, child-reported adherence using the questionnaire was significantly associated with dichotomized MEMS ® adherence (OR 1.8, 95% CI 1.4 to 2.4), 48-hour treatment interruptions (OR 0.41, 95% CI 0.3 to 0.6), and viral suppression (OR 3.4, 95% CI 1.7 to 6.7). We did find, however, that different cut-points for the adherence score may be context-specific. For example, MEMS ® non-adherent children in Kenya had a lower adherence score (0.98) compared to South Africa (1.77) or Thailand (1.58)., Conclusions: We found suboptimal adherence to ART was common by multiple measures in this multi-country cohort of children. The short-form questionnaire demonstrated reasonable validity to screen for non-adherence in these diverse settings., (© 2019 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.)

When life-sustaining treatments (LST) are no longer effective or consistent with patient preferences, limitations may be set so that LSTs are withdrawn or withheld from the patient. Many studies have examined the frequency of limitations of LST in intensive care unit (ICU) settings in the past 30 years. This systematic review describes variation and patient characteristics associated with limitations of LST in critically ill patients in all types of ICUs in the United States. A comprehensive search of the literature was performed by a medical librarian between December 2014 and April 2017. A total of 1,882 unique titles and abstracts were reviewed, 113 were selected for article review, and 36 studies were fully reviewed. Patient factors associated with an increased likelihood of limiting LST included white race, older age, female sex, poor preadmission functional status, multiple comorbidities, and worse illness severity score. Based on several large, multicenter studies, there was a trend toward a higher frequency of limitation of LST over time. However, there is large variability between ICUs in the proportion of patients with limitations and on the proportion of deaths preceded by a limitation. Increases in the frequency of limitations of LST over time suggests changing attitudes about aggressive end-of-life-care. Limitations are more common for patients with worse premorbid health and greater ICU illness severity. While some differences in the frequency of limitations of LST may be explained by personal factors such as race, there is unexplained wide variability between units.

Objective: Describe the implementation and effects of Mobile Acute Care for Elders (MACE) consultation at a Veterans Affairs Medical Center (VAMC)., Design: Retrospective cohort analysis., Intervention: Veterans aged 65 or older who were admitted to the medicine service between October 1, 2012, and September 30, 2014, were screened for geriatric syndromes via review of medical records within 48 hours of admission. If the screen was positive, the MACE team offered the admitting team a same-day consultation involving comprehensive geriatric assessment and ongoing collaboration with the admitting team and supportive services to implement patient-centric recommendations for geriatric syndromes., Results: Veterans seen by MACE (n = 421) were compared with those with positive screens but without consultation (n = 372). The two groups did not significantly differ in age, comorbidity, sex, or race. All outcomes (30-day readmission, 30-day mortality, readmission costs) were in the expected direction for patients receiving MACE but did not reach statistical significance. Patients receiving MACE had lower odds of 30-day readmission (11.9% vs 14.8%; odds ratio [OR] = 0.82; 95% confidence interval [CI] = 0.54-1.25; p = .360) and 30-day mortality (5.5% vs 8.6%; OR = 0.64; CI = 0.36-1.12; p = .115), and they had lower 30-day readmission costs (MACE $15,502; CI = $12,242-$19,631; comparison = $18,335; CI = $14,641-$22,962; p = .316) than those who did not receive MACE after adjusting for age and Charlson Comorbidity Index., Conclusion: Our MACE consultation model for older veterans with geriatric syndromes leverages the limited supply of clinicians with expertise in geriatrics. Although not statistically significant in this study of 793 subjects, MACE patients had lower odds of 30-day readmission and mortality, and lower readmission costs. J Am Geriatr Soc 67:818-824, 2019., (© 2018 The American Geriatrics Society.)

Study Objectives: Polysomnography (PSG) is increasingly used in the assessment of infants. Newborn PSG reference values based on recent standardization are not available. This study provides reference values for PSG variables in healthy newborn infants., Methods: Cross-sectional study of normal term newborn infants using standardized PSG collection and American Academy of Sleep Medicine interpretation criteria., Results: Thirty infants born between 37 and 42 weeks gestation underwent PSG testing before 30 days of age (mean 19.6 days). The infants had a mean sleep efficiency of 71% with average proportions of transitional, NREM and REM sleep estimated at 16.1%, 43.3% and 40.6% respectively. Mean arousal index was 14.7 events/h with respiratory arousal index of 1.2 events/h. Mean apnea-hypopnea index (AHI) was 14.9 events/h. Central, obstructive, and mixed apnea indices were 5.4, 2.3, and 1.2 events/h respectively. Mean oxygen saturation in sleep was 97.9% with a nadir of 84.4%. Mean end tidal CO 2 was 35.4 mmHg with an average of 6.2% of sleep time spent above end-tidal CO 2 45 mmHg and 0.6% above 50 mmHg., Conclusions: The sleep efficiency was significantly lower and the AHI was significantly higher compared to healthy children older than 1 year. The AHI was also higher than reported in healthy infants older than 1 month. These findings suggest current severity classifications of sleep apnea may not apply to newborn infants., (© 2019 American Academy of Sleep Medicine.)

Context: Adults who have advanced cancer experience distress, and many use religion and spirituality to cope. Research on the spiritual experiences of patients with advanced cancer will help guide the provision of high-quality spiritual care., Objectives: To qualitatively describe advanced cancer patients' spiritual experiences of illness., Methods: We conducted semistructured qualitative interviews at a single cancer center with 21 patients with stage IV solid malignancies who had a prognosis of less than 12 months, as estimated by each patient's medical oncologist. Five investigators conducted a thematic analysis of the transcribed interviews., Results: We found 31 patients who were eligible for enrollment, and 21 (67.7%) participated in interviews to thematic saturation. Using a thematic-analysis approach, five major themes emerged. Relationships with family and friends was the most important theme among all 21 patients irrespective of their religious or spiritual identity. Relationship with God and faith community was frequently identified by those who considered themselves spiritually religious. Cancer often led to reflection about the meaning of life and the nature of existential suffering. Patients addressed the extent to which identity was changed or maintained through the cancer experience, and some expressed acceptance as a way of coping with illness., Conclusions: Spiritual care for dying cancer patients should always include the exploration of relationships with family and friends, as well as God and faith community for some patients. Relationships with family, friends, and God can be a source of strength for many. Making meaning, addressing identity concerns, supporting acceptance as a resource for coping with illness, and acknowledging existential suffering will often arise for these patients., (Copyright © 2018 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Patient satisfaction surveys as a metric for quality-based financial incentives carry a risk of bias toward women and underrepresented physicians. Previous assessments in our department of medicine found that most women faculty were rated in the bottom quartile of patient satisfaction scores, whereas analysis of scores for underrepresented physicians had not been performed. To investigate, we compared patient satisfaction scores and relevant demographics of faculty physicians during 1 year when quality-related financial incentives were offered based on this metric. Methods: Patient satisfaction and communication scores collected during academic year 2015-2016 were obtained for 369 physicians (119 women and 250 men) at Indiana University Health system. Independent variables included physician gender, race, ethnicity, and subspecialty or division; 190 physicians constituted the study cohort for whom data were available for comparison. Statistical analyses were performed to determine if there were differences between gender and race in patient satisfaction scores (mean, median, t -tests, and Chi-square tests). A factorial analysis of variance model was performed to incorporate both main effects and to determine if there was a significant interaction between them. Results: Median and mean of scores were lower for women physicians and underrepresented physicians. Analysis demonstrated nonsignificant effect between gender-segregated cohorts. Racially underrepresented physicians had significantly lower mean scores than their white colleagues [ F (4, 185)=2.46, p =0.046]. Conclusion and Relevance: Our results indicate a significant difference in patient satisfaction scores between underrepresented and white physicians. These data may suggest a potential bias, among patients and institutional practices, ultimately leading to pay inequities through differences in financial incentives toward underrepresented physicians., Competing Interests: All authors attest that they have no financial conflicts of interest, real or apparent, nor relations with industry relevant to the content of this article.

Background: Recent studies have suggested that removing foods from the diet to manage atopic dermatitis (AD), based on positive allergy test results, may lead to immediate allergic reactions on reintroduction of that food., Objective: To examine the frequency of oral food challenge (OFC) failures among foods removed from the diet as suspected AD triggers, focusing on the 5 major food allergens in the United States., Methods: OFCs to egg, milk, peanut, soy, and wheat, performed from 2008 to 2014, at a children's hospital's allergy clinics, were reviewed. OFCs were offered based on history and laboratory values. Reasons for food avoidance were classified as food allergy (IgE-mediated reaction occurring within 2 hours); sensitization only (lack of introduction because of positive test results); and removal because of test results during AD evaluation., Results: There were 442 OFCs performed, with 89 failures (20.1%). Reasons for OFCs included a history of food allergy (320 of 442 [72.4%]), food sensitization without any introduction (77 of 442 [17.4%]), and AD (45 of 442 [10.2%]). OFC failures among those who had food allergy (70 of 320 [21.9%]), sensitization only (13 of 77 [16.9%]), and suspected AD trigger (6 of 45 [13.3%]) did not significantly differ (P = .63). Wheat was more likely to be avoided than the other 4 foods for AD concerns (P < .001)., Conclusion: The frequency of OFC failure among those who removed foods suspected as AD triggers was 13.3%, indicating a loss of tolerance. Restriction of foods to manage AD must be done with caution and close monitoring., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background:: The Physician Orders for Life-Sustaining Treatment (POLST) form is an advance care planning tool designed for seriously ill patients. The discussions needed for high-quality POLST decision-making are time intensive and often do not occur in the outpatient setting., Objective:: We conducted a single-arm feasibility study of POLST facilitation by nonphysicians using Respecting Choices Last Steps, a standardized, structured approach to facilitation of POLST conversations., Setting/participants:: Community-dwelling adults aged 65 and older enrolled in a complex care management program in a Midwestern urban hospital., Measurements:: We assessed the feasibility and acceptability by determining the proportion of eligible patients who enrolled and completed the study, by adherence to the Respecting Choices protocol, and by responses to qualitative and quantitative survey items about the intervention., Results:: We enrolled 18 (58.1%) of 31 eligible patients, with a mean age of 77.8 years (standard deviation: 6.95); 12 were African American. The POLST facilitation was delivered to all 18; 10 (55.6%) completed POLST forms. Direct observation of intervention delivery using a checklist found 85% of the required elements were performed by facilitators. We completed 6- to 8-week follow-up interviews in 16 of 18 patients (88.9%). We found 87.5% of decision makers agreed or strongly agreed that "Talking about the (POLST) form helped me think about what I really want.", Conclusions:: The POLST facilitation can be successfully delivered to frail older adults in a complex care management setting, with high fidelity to protocol. Further research is needed to demonstrate the effects of this approach on decision quality and other patient-reported outcomes.