Insomnia and risk of mortality in older adults.

Existing evidence linking insomnia to all-cause mortality in older individuals remains inconclusive. We conducted a retrospective study of a large cohort of veterans aged 65-80 years old identified from the Corporate Data Warehouse, a large data repository derived from the Veterans Health Administration integrated medical records. Veterans' enrollees with and without International Classification of Diseases, Ninth and Tenth Revision, codes corresponding to insomnia diagnosis between 1 January 2010 and 30 March 2019 were assessed for eligibility. The primary outcome was all-cause mortality. A total of 36,269 veterans, 9584 with insomnia and 26,685 without insomnia, were included in the analysis. Baseline mean (SD) age was 72.6 (4.2) years. During a mean follow-up of 6.0 (2.9) years of the propensity score matched sample, the mortality rate was 34.8 [95% confidence interval: 33.2-36.6] deaths per 1000 person-years among patients with insomnia compared with 27.8 [95% confidence interval: 26.6-29.1] among patients without insomnia. In a Cox proportional hazards model, insomnia was significantly associated with higher mortality (hazard ratio: 1.39; [95% confidence interval: 1.27-1.52]). Patients with insomnia also had a higher risk of non-fatal cardiovascular events (hazard ratio: 1.21; [95% confidence interval: 1.06-1.37]). Secondary stratified analyses by sex, race, ethnicity and hypertension showed no evidence of effect modification. A higher risk of mortality (hazard ratio: 1.51; [95% confidence interval: 1.33-1.71]) was observed when depression was present compared with absent (hazard ratio: 1.26; [95% confidence interval: 1.12-1.44]; p = 0.02). In this cohort study, insomnia was associated with increased risk-adjusted mortality and non-fatal cardiovascular events in older individuals.

Sleep-wake state discrepancy among cancer survivors with insomnia symptoms.

PURPOSE: To evaluate the discrepancy and correlation between sleep-wake measures (i.e., time in bed (TIB), total sleep time (TST), sleep onset latency (SOL), wake after sleep onset (WASO), and sleep efficiency (SE%)) reported on sleep diary and measured by actigraphy among cancer survivors with insomnia symptoms; and examine the influences of sociodemographic and clinical variables on these measurement differences. METHODS: A heterogenous sample of cancer survivors with insomnia symptoms (n = 120; M age = 63.7 ± 10.1; female = 58.3%) was included. Seven consecutive days of sleep diary and actigraphic data were obtained along with information on demographic, sleep, and mental health symptoms. Bland-Altman plot, Pearson correlation coefficient, concordance correlation coefficient, and mixed linear model approach were used to conduct the analysis. RESULTS: Self-reported TIB, SOL, and WASO were longer than measured by actigraphy (TIB: 8.6 min. (95% CI, 3.7, 13.5; p < .001); SOL: 14.8 min. (95% CI, 9.4, 20.2; p < .0001); and WASO: 20.7 min. (95% CI, 9.4, 20.2; p < .0001), respectively); and self-reported TST and SE% were shorter than measured by actigraphy (TST: 6.8 min. (95% CI, -18.7, 5.13); and SE%: 0.7% (95%CI, -3.0, 2.0), respectively), but were not statistically significant. Sex, higher insomnia severity, and poor sleep quality were associated with discrepancy between several sleep-wake measures. CONCLUSION: Subjective and objective sleep-wake measures may present discrepant finding among cancer survivors with symptoms of insomnia. Future research is needed to validate appropriate sleep-wake assessment, and better understand factors that influence the discrepancy that exists between measures among this population. CLINICAL TRIAL REGISTRATION: Clinical trials identifier: NCT03810365. Date of registration: January 14, 2019.

Clinical and economic effectiveness of a pharmacy and primary care collaborative transition of care program.

BACKGROUND: Primary care pharmacists are uniquely positioned to improve care quality by intervening within care transitions in the postdischarge period. However, additional evidence is required to demonstrate that pharmacist-led interventions can reduce health care utilization in a cost-effective manner. The study's objective was to evaluate the clinical and economic effectiveness of a pharmacy-led transition of care (TOC) program within a primary care setting. METHODS: This cluster randomized trial was conducted between 2019 and 2021 and included three primary care practices. Eligible patients were ≥18 years of age and at high risk of readmission. The multifaceted pharmacy intervention included medication reconciliation, comprehensive medication review, and patient and provider follow-up. The primary composite endpoint included hospital readmissions and emergency department (ED) visits within 30 days of discharge. Differences in outcomes were modeled using a generalized estimated equations approach and outcomes were assumed to be distributed as a Poisson random variable. A cost-benefit analysis was embedded within the study and estimated economic outcomes from a provider group/health system perspective. Cost measures included: net benefit, benefit to cost ratio (BCR), and return on investment (ROI). RESULTS: Of 300 eligible patients, 36 were in the intervention group and 264 in the control group. The intervention significantly reduced the primary composite outcome of all-cause readmissions and ED visits within 30 days (adjusted incidence rate ratio [aIRR], 0.54; 95% CI, 0.44-0.66; P < 0.001). There were significant reductions in both 30-day all-cause readmissions (aIRR, 0.64; 95% CI, 0.60-0.67; P < 0.001) and ED visits (aIRR, 0.25; 95% CI, 0.20, 0.31; P < 0.001) between groups. The net benefit of the intervention was $9,078, with a BCR of 2.11 and a ROI of 111%. Sensitivity analyses were robust to changes in economic inputs. CONCLUSION: This care transition program had positive clinical and economic benefits, providing further support for the essential role pharmacists demonstrate in providing TOC services.

Susceptibility networks reveal independent patterns of brain iron abnormalities in multiple sclerosis.

Brain iron homeostasis is necessary for healthy brain function. MRI and histological studies have shown altered brain iron levels in the brains of patients with multiple sclerosis (MS), particularly in the deep gray matter (DGM). Previous studies were able to only partially separate iron-modifying effects because of incomplete knowledge of iron-modifying processes and influencing factors. It is therefore unclear to what extent and at which stages of the disease different processes contribute to brain iron changes. We postulate that spatially covarying magnetic susceptibility networks determined with Independent Component Analysis (ICA) reflect, and allow for the study of, independent processes regulating iron levels. We applied ICA to quantitative susceptibility maps for 170 individuals aged 9-81 years without neurological disease ("Healthy Aging" (HA) cohort), and for a cohort of 120 patients with MS and 120 age- and sex-matched healthy controls (HC; together the "MS/HC" cohort). Two DGM-associated "susceptibility networks" identified in the HA cohort (the Dorsal Striatum and Globus Pallidus Interna Networks) were highly internally reproducible (i.e. "robust") across multiple ICA repetitions on cohort subsets. DGM areas overlapping both robust networks had higher susceptibility levels than DGM areas overlapping only a single robust network, suggesting that these networks were caused by independent processes of increasing iron concentration. Because MS is thought to accelerate brain aging, we hypothesized that associations between age and the two robust DGM-associated networks would be enhanced in patients with MS. However, only one of these networks was altered in patients with MS, and it had a null age association in patients with MS rather than a stronger association. Further analysis of the MS/HC cohort revealed three additional disease-related networks (the Pulvinar, Mesencephalon, and Caudate Networks) that were differentially altered between patients with MS and HCs and between MS subtypes. Exploratory regression analyses of the disease-related networks revealed differential associations with disease duration and T2 lesion volume. Finally, analysis of ROI-based disease effects in the MS/HC cohort revealed an effect of disease status only in the putamen ROI and exploratory regression analysis did not show associations between the caudate and pulvinar ROIs and disease duration or T2 lesion volume, showing the ICA-based approach was more sensitive to disease effects. These results suggest that the ICA network framework increases sensitivity for studying patterns of brain iron change, opening a new avenue for understanding brain iron physiology under normal and disease conditions.

Effect of musculature on mortality, a retrospective cohort study.

BACKGROUND: While often life-saving, treatment for head and neck cancer (HNC) can be debilitating resulting in unplanned hospitalization. Hospitalizations in cancer patients may disrupt treatment and result in poor outcomes. Pre-treatment muscle quality and quantity ascertained through diagnostic imaging may help identify patients at high risk of poor outcomes early. The primary objective of this study was to determine if pre-treatment musculature was associated with all-cause mortality. METHODS: Patient demographic and clinical characteristics were abstracted from the cancer center electronic database (n = 403). Musculature was ascertained from pre-treatment CT scans. Propensity score matching was utilized to adjust for confounding bias when comparing patients with and without myosteatosis and with and without low muscle mass (LMM). Overall survival (OS) was evaluated using the Kaplan-Meier method and Cox multivariable analysis. RESULTS: A majority of patients were male (81.6%), white (89.6%), with stage IV (41.2%) oropharyngeal cancer (51.1%) treated with definitive radiation and chemotherapy (93.3%). Patients with myosteatosis and those with LMM were more likely to die compared to those with normal musculature (5-yr OS HR 1.55; 95% CI 1.03-2.34; HR 1.58; 95% CI 1.04-2.38). CONCLUSIONS: Musculature at the time of diagnosis was associated with overall mortality. Diagnostic imaging could be utilized to aid in assessing candidates for interventions targeted at maintaining and increasing muscle reserves.

A pilot school-based health center intervention to improve asthma chronic care in high-poverty schools.

OBJECTIVE: To test the feasibility and effectiveness of a multifaceted intervention administered through school-based health centers (SBHCs) to improve asthma control for children in high-poverty schools with not well controlled asthma. METHODS: Students 4-14 years old with persistent asthma were enrolled from three SBHCs. The centers' advanced practice providers received training on evidence-based asthma guidelines. Students randomized to the intervention received directly observed therapy of their asthma controller medication, medication adjustments as needed by the centers' providers, and daily self-management support. Students randomized to usual care were referred back to their primary care provider (PCP) for routine asthma care. RESULTS: We enrolled 29 students. Students in the intervention group received their controller medication 92% of days they were in school. Ninety-four percent of follow-up assessments were completed. During the study, 11 of 12 intervention students had a step-up in medication; 2 of 15 usual care students were stepped up by their PCP. Asthma Control Test scores did not differ between groups, although there were significant improvements from baseline to the 7 month follow-up within each group (both p < .01). Both FEV1% predicted and FEV1/FVC ratio significantly worsened in the usual care group (both p = .001), but did not change in the intervention group (p = .76 and .28 respectively). CONCLUSIONS: Our pilot data suggest that a multifaceted intervention can be feasibly administered through SBHCs in communities with health disparities. Despite the small sample size, spirometry detected advantages in the intervention group. Further study is needed to optimize the intervention and evaluate outcomes. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT03032744.

Cross-sectional analysis of myosteatosis and physical function in pretreatment head and neck cancer patients.

BACKGROUND: Head and neck cancer (HNC) and its treatment are associated with muscle weakness and considerable long-term comorbidity. The goal of this study was to determine whether skeletal muscle density (SMD) as quantified from pretreatment computed tomography (CT) scans will correlate with measures of function and strength prior to treatment in physical function in HNC patients. PATIENTS AND METHODS: A cross-sectional analysis was conducted on 90 HNC patients. SMD (myosteatosis vs. normal) was calculated from pretreatment CT scans using SliceOmatic software. Pretreatment physical function was assessed via handgrip strength (HGS), the timed up and go test (TUG), and the short physical performance battery (SPPB). Demographic, cancer, and social characteristics were also collected as confounders. Linear regression models assessed the association between myosteatosis and measures of physical function. RESULTS: The 90 patients were predominately White, male, former smokers with an average BMI of 28.7 ± 5.7 kg/m2. Among men, adjusted models indicate, as compared to those with normal muscle density, the total SPPB score of those with myosteatosis was 1.57 points lower (p = 0.0008), HGS was 0.85 kg lower (p = 0.73), and TUG took 1.34 s longer (p = 0.03). There were no differences in women. CONCLUSION: Myosteatosis is associated with physical function prior to treatment in HNC patients. Larger studies are needed to examine the importance of exercise programs prior to and during treatment to build lean mass and improve long-term prognosis in HNC.

A Multilevel Approach to Investigate Relationships Between Healthcare Resources and Lung Cancer.

BACKGROUND: Screening for lung cancer is an evidence-based but underutilized measure to reduce the burden of lung cancer mortality. Lack of adequate data on geographic availability of lung cancer screening inhibits the ability of healthcare providers to help patients with decision-making and impedes equity-focused implementation of screening-supportive services. OBJECTIVES: This analysis used data from the 2012-2016 Surveillance, Epidemiology, and End Results (SEER) Program, the Behavioral Risk Factor Surveillance System, and the county health ranking to examine (a) which cancer resources and county-level factors are associated with late-stage lung cancer at diagnosis and (b) associations between county rurality and lung cancer incidence/mortality rates. METHODS: Using the New York state SEER data, we identified 68,990 lung cancer patients aged 20-112 years; 48.3% had late-stage lung cancers, and the average lung cancer incidence and mortality rates were 70.7 and 46.2 per 100,000, respectively. There were 144 American College of Radiology-designated lung cancer screening centers and 376 Federally Qualified Health Centers identified in New York state. County rurality was associated with a higher proportion of late-stage lung cancers and higher lung cancer mortality rates. DISCUSSION: Visual geomapping showed the scarcity of rural counties' healthcare resources. County rurality is a significant factor in differences in lung cancer screening resources and patient outcomes. Use of publicly available data with geospatial methods provides ways to identify areas for improvement, populations at risk, and additional infrastructure needs.

Brief Behavioral Treatment for Insomnia: A Meta-Analysis.

PURPOSE: The current study aims to quantify the effect of brief behavioral treatment for insomnia (BBTI) studies through meta-analysis. METHOD: Searches were performed from inception to February 2020, reporting on the effects of BBTI using randomized controlled trials (RCT) (adults aged 32 to 84). The main outcome measures were sleep onset latency (SOL), wake after sleep onset (WASO), sleep efficiency (SE%), and total sleep time (TST). RESULTS: BBTI showed improved SOL compared with control group in mean difference at early (-15.42 [95% CI: -33.05 to -12.01; I2 =49%]) and late follow-up (-10.52 [95% CI: -1.12 to 0.54; I2=93%]). This was statistically significant at early follow-up, but not at late follow-up. The improvement of WASO by BBTI over the control group was shown at early follow-up (-17.47 [95% CI: -2.67 to 0.45; I2=90%]), and was statistically significant. For WASO, a non-statistically significant improvement of BBTI over the control group was shown at late follow-up (-12.77 [95% CI: -22.47 to -3.08; I2=0%]). SE% was shown improved statistically significant by BBTI over control group at early (4.47 [95% CI: -0.35 to 9.29; I2=98%]) and at late follow-up (6.52 [95% CI: -4.00 to 17.05; I2=89%]). The TST was shown no improvement by BBTI at early follow-up in mean difference (-2.97 [95% CI -38.83 to 32.90; I2=96%]). At late follow-up, TST was shown improvement in BBTI with mean difference (14.52 [95% CI: -31.64 to 60.68; I2=94%]) compared with the control group. CONCLUSION: Current evidence suggests that BBTI can be considered preliminarily efficacious and can be used for samples of middle-aged and older adults.

The Nightmare Quality of Life Questionnaire.

RATIONALE: Patient-centered outcomes are increasingly sought to evaluate social interactions and healthcare interventions in patients with sleep disorders. Yet, measures to assess quality of life (QoL) are lacking for those who experience nightmares. OBJECTIVE: The aim of the study is to describe the development and validation of a new health-related quality of life (HRQoL) instrument for patients with nightmares. METHODS: Attributes obtained from a focus group of patients (n = 113) with established nightmares were analyzed using exploratory factor analysis to elicit salient QoL themes for the new instrument. A validation cohort (n = 34) was used to determine the psychometric performance of the 16-item questionnaire including item-scaling, concurrent validity, and test-retest reliability tested four weeks apart. RESULTS: Four factors (sleep health, emotional and psychological well-being, social interaction, and motivation) explained 53.9% of the total variance. The Nightmare Quality of Life (NQoL) showed good internal consistency (Cronbach's alpha 0.85) and test-retest reliability (ICC = 0.89). Concurrent validity was evidenced by a strong correlation with the Nightmare Distress Questionnaire (r = 0.87; p < .001) and more modest associations with the Nightmare Frequency Questionnaire (r = , 0.69; p < .001), SF-36 (r = -0.68; p < .001), and PSQI (r = 0.45; p = .007). CONCLUSIONS: The NQoL has demonstrable construct validity and reliability and represents a promising multi-dimensional instrument to assess outcome measures for quality of life in patients with nightmares.

Teaching surgery novices and trainees advanced laparoscopic suturing: a trial and tribulations.

INTRODUCTION: The benefits of minimally invasive surgery are numerous; however, considerable variability exists in its application and there is a lack of standardized training for important advanced skills. Our goal was to determine whether participation in an advanced laparoscopic curriculum (ALC) results in improved laparoscopic suturing skills. METHODS AND PROCEDURES: Study design was a prospective, randomized controlled trial. Surgery novices and trainees underwent baseline FLS training and were pre-tested on bench models. Participants were stratified by pre-test score and randomized to undergo either further FLS training (control group) or ALC training (intervention group). All were post-tested on the same bench model. Tests for differences between post-test scores of cohorts were performed using least squared means. Multivariable regression identified predictors of post-test score, and Wilcoxon rank sum test assessed for differences in confidence improvement in laparoscopic suturing ability between groups. RESULTS: Between November 2018 and May 2019, 25 participants completed the study (16 females; 9 males). After adjustment for relevant variables, participants randomized to the ALC group had significantly higher post-test scores than those undergoing FLS training alone (mean score 90.50 versus 82.99, p = 0.001). The only demographic or other variables found to predict post-test score include level of training (p = 0.049) and reported years of video gaming (p = 0.034). There was no difference in confidence improvement between groups. CONCLUSIONS: Training using the ALC as opposed to basic laparoscopic skills training only is associated with superior advanced laparoscopic suturing performance without affecting improvement in reported confidence levels. Performance on advanced laparoscopic suturing tasks may be predicted by lifetime cumulative video gaming history and year of training but does not appear to be associated with other factors previously studied in relation to basic laparoscopic skills, such as surgical career aspiration or musical ability.

Impact of low arousal threshold on treatment of obstructive sleep apnea in patients with post-traumatic stress disorder.

PURPOSE: We sought to determine the prevalence of low arousal threshold (LAT) in veterans with post-traumatic stress disorder (PTSD) and whether or not LAT is associated with decreased use of continuous positive airway pressure (CPAP). METHODS: We conducted a retrospective study of all veterans with documented PTSD who had an apnea hypopnea index > 5/h over a 27-month period. Demographic, clinical characteristics, and CPAP usage were extracted from the medical records. A multivariate analysis was conducted to assess predictors of CPAP use at 3 months in patients with LAT after adjusting for severity of PTSD. RESULTS: LAT was identified in 55% of 119 patients with PTSD and newly diagnosed OSA. LAT was associated with younger age (odds ratio [OR] 0.91; 95% confidence interval [CI] 0.86-0.95), lower BMI (OR 0.82; 95% CI 0.73-0.91), presence of insomnia (OR 1.34; 95% CI 1.19-1.81), and use of antidepressant (OR 1.14; 95% CI 1.09-2.01). PTSD severity, REM rebound, and the presence of baseline comorbid insomnia were each associated with CPAP use at 3 months. Neither daytime sleepiness, body mass index (BMI), nor LAT endotype was correlated with CPAP utilization. Insomnia was the only factor associated with decreased CPAP use in patients with PTSD and LAT (P = 0.04). CONCLUSION: The LAT endotype is common among veterans with PTSD. An improved understanding of how insomnia in this population affects CPAP utilization would be instrumental in designing targeted therapy to improve sleep quality.

Assessing the assessment: a comparison of the IPASS and ICCAS to measure change in interprofessional competencies following a large-scale interprofessional forum.

Measuring the effectiveness of interprofessional education (IPE) experiences is essential but challenging. Surveying learners before (pretest) and after (posttest) an IPE experience may result in minimal change due to response shift bias. Retrospective pretest/posttest assessment may ameliorate response shift bias but may also result in inflated change scores due to social desirability bias. We studied a cohort of 675 students from 12 health professions who completed the Interprofessional Attitudes Scale (IPAS) within the 4 weeks before (pretest) and the 3 weeks after (posttest) an IPE forum and completed the Interprofessional Collaborative Competency Attainment Survey (ICCAS) within the 3 weeks after the forum as a retrospective pretest/posttest. We found higher scores on the pretest IPAS than the retrospective pretest ICCAS and greater change in scores on the ICCAS than the IPAS, indicating potential response shift and social desirability biases. Furthermore, we found few significant correlations between change scores in subscales of the two tests, but a high number of strong and significant correlation among the ICCAS subscale change scores. Our results indicate the timing of pretest administration may impact change scores or that subscales of IPAS may be more unique than those of ICCAS. These findings suggest that educators should consider the potential impact of response shift and social desirability biases when interpreting results of the IPAS and ICCAS in response to an IPE learning experience.

Trait Conscientiousness predicts rate of longitudinal SDMT decline in multiple sclerosis.

BACKGROUND: Many people with multiple sclerosis (MS) exhibit cognitive decline over several years. Baseline differences may put people at greater risk for such decline. OBJECTIVE: To characterize rates of longitudinal cognitive decline and investigate baseline clinical predictors. METHODS: We report a retrospective analysis of 531 MS patients whose data were gleaned from a multi-study database, aggregated over 16 years. Linear mixed effects modeling was applied to estimate the average rate of decline on Symbol Digit Modalities Test (SDMT) performance and to predict rates of decline using baseline clinical variables. RESULTS: Participants exhibited an average estimated decline of 0.22 SDMT raw-score points/year (95% confidence interval (CI) (-0.32, -0.12)). We observed a significant main effect of time from baseline (t = -2.78, p = 0.006), test form (t = 2.13, p = 0.034), disease course (t = 2.91, p = 0.004), age (t = -2.76, p = 0.006), sex (t = -2.71, p = 0.007), subjective cognitive impairment (t = -2.00, p = 0.046), premorbid verbal intelligence (t = 5.14, p < 0.001), and trait Conscientiousness (t = 2.69, p = 0.008). A significant interaction emerged for Conscientiousness and time from baseline (t = 2.57, p = 0.011). CONCLUSION: Higher baseline trait Conscientiousness predicts slower rates of longitudinal cognitive decline in MS. This relationship, the average rate of decline, and practice effects can inform future research and clinical treatment decisions.

Trait Conscientiousness predicts rate of brain atrophy in multiple sclerosis.

BACKGROUND: Conscientiousness is a core personality trait with favorable prognosis in neuropsychiatric disease. OBJECTIVE: We aimed to determine whether baseline Conscientiousness predicts future brain atrophy in multiple sclerosis (MS) after accounting for demographic and basic clinical characteristics. METHODS: Trait Conscientiousness, clinical features, and Expanded Disability Status Scale (EDSS) were obtained at baseline. Lateral ventricle volume (LVV) was measured longitudinally. In a retrospective general linear mixed effects model, data from 424 patients were analyzed (mean 6 time-points, up to 15 years). RESULTS/CONCLUSION: We observed significant age and Conscientiousness by time-from-baseline interactions indicating that younger age and higher Conscientiousness are associated with reduced progression of brain atrophy.

Predictive Model for Operative Intervention after Blunt Abdominal Trauma in Children with Equivocal CT Findings: A Pilot Study.

BACKGROUND: To study the clinical and radiologic factors predicting the need for surgical intervention after blunt abdominal trauma (BAT) in children with equivocal computed tomography (CT) scan findings. METHODS: We performed a retrospective review of the trauma database at our level I pediatric trauma center between 2011 and 2019. We selected patients with BAT and equivocal findings for surgical intervention on CT scan. We studied five factors: abdominal wall bruising (AWB), abdominal pain/tenderness (APT), thoracolumbar fracture, the presence of free fluid (FF), and the presence of solid organ injury, all previously reported in the literature to predict the need for operative intervention. We used t-test, the Kruskal-Wallis test and logistic regression to study the association of these factors with the need for operation in our pediatric cohort. RESULTS: Of 3044 blunt trauma patients, 288 had abdominal CT scans with 61 patients demonstrating equivocal findings. Operation was performed for 12 patients (19.7%) confirming surgically correctable traumatic injuries. The need for surgical intervention was significantly associated with the age of the patients (P = 0.03), the presence of APT (P = 0.001), AWB (P = 0.01), and FF (P = 0.04). The presence of thoracolumbar fracture and solid organ injury were not significantly associated with the need for operation. For the subset of 37 patients who were injured in a motor vehicle crash, five (13.5%) required surgical intervention, which was significantly associated with the presence of AWB (P = 0.04), APT (P = 0.01), and FF (P = 0.03). A predictive model that used these factors produced a receiver operating characteristic curve of 0.86. CONCLUSIONS: In cases of equivocal abdominal CT scan findings to evaluate BAT in children, the presence of abdominal wall tenderness, AWB, or FF may be significant factors predicting more accurately the need for operative intervention. A predictive model using the combination of clinical and image findings might determine with more certainty, the need for surgical intervention in children with BAT and equivocal CT findings. Validation on a larger multi-institutional data set should be done.

Do Histological Features of Eosinophilic Esophagitis in Children Correlate With Peripheral Eosinophils?

AIM: Eosinophilic esophagitis (EoE) is a chronic, relapsing inflammatory disease of the esophagus. We investigate whether peripheral eosinophils can be a good indicator of esophageal eosinophilia and whether they correlate with histological findings, such as basilar hyperplasia, spongiosis, microabscesses, number of lymphocytes, and number of neutrophils. METHODS: A retrospective chart review was conducted with EoE patients ages <18 years after obtaining IRB approval. Biopsies obtained from 57 EoE patients were analyzed. Patient demographics, symptoms; complete blood count with differentials obtained at the time of endoscopies or within a month of the procedure, were documented. RESULTS: A significant correlation was observed between peripheral absolute eosinophil count (AEC) and peak esophageal eosinophil count (P value: 0.0009). Subjects with biopsies suggestive of ongoing disease activity or active status had a higher mean of AEC at 577.41 ±â€Š202.60 compared with subjects with inactivity with mean of 305.26 ±â€Š526.67. However, when the subjects were broadly divided with 500 AEC as a cut off (<500 and >500 AEC), it was found that, out of 27 EoE inactive patients, 24 had AEC count less than or equal to 500 and out of 66 EoE active patients, 32 had AEC more than 500. CONCLUSION: Active EoE status meant a higher mean of AEC compared with inactive status; but AEC was not found to be a sensitive tool for detecting active EoE.

Computational Segmentation and Classification of Diabetic Glomerulosclerosis.

BACKGROUND: Pathologists use visual classification of glomerular lesions to assess samples from patients with diabetic nephropathy (DN). The results may vary among pathologists. Digital algorithms may reduce this variability and provide more consistent image structure interpretation. METHODS: We developed a digital pipeline to classify renal biopsies from patients with DN. We combined traditional image analysis with modern machine learning to efficiently capture important structures, minimize manual effort and supervision, and enforce biologic prior information onto our model. To computationally quantify glomerular structure despite its complexity, we simplified it to three components consisting of nuclei, capillary lumina and Bowman spaces; and Periodic Acid-Schiff positive structures. We detected glomerular boundaries and nuclei from whole slide images using convolutional neural networks, and the remaining glomerular structures using an unsupervised technique developed expressly for this purpose. We defined a set of digital features which quantify the structural progression of DN, and a recurrent network architecture which processes these features into a classification. RESULTS: Our digital classification agreed with a senior pathologist whose classifications were used as ground truth with moderate Cohen's kappa κ = 0.55 and 95% confidence interval [0.50, 0.60]. Two other renal pathologists agreed with the digital classification with κ1 = 0.68, 95% interval [0.50, 0.86] and κ2 = 0.48, 95% interval [0.32, 0.64]. Our results suggest computational approaches are comparable to human visual classification methods, and can offer improved precision in clinical decision workflows. We detected glomerular boundaries from whole slide images with 0.93±0.04 balanced accuracy, glomerular nuclei with 0.94 sensitivity and 0.93 specificity, and glomerular structural components with 0.95 sensitivity and 0.99 specificity. CONCLUSIONS: Computationally derived, histologic image features hold significant diagnostic information that may augment clinical diagnostics.

Effects of Partially Hydrolyzed Formula on Severity and Outcomes of Neonatal Abstinence Syndrome.

OBJECTIVE: This study compares the effect of partially hydrolyzed formula (PHF) and standard formula (SF) on the severity and short-term outcomes of neonatal abstinence syndrome (NAS). STUDY DESIGN: We performed a retrospective chart review of 124 opioid-dependent mothers and their term or near-term infants. Infants were categorized according to the predominant type of formula consumed during the hospital stay. Finnegan's scale was used to assess symptoms of withdrawal. RESULTS: A total of 110 infants met our inclusion criteria. Thirty-four (31%) infants were fed predominantly PHF, 60 (54%) infants were fed SF, and 16 (15%) infants were fed maternal breast milk. There was no difference between the infants in the PHF and SF groups with respect to requirement of morphine (MSO4) therapy, maximum dose of MSO4 used, duration of MSO4 treatment or length of hospital stay after performing multivariate analyses to control for type of drug used by the mother, maternal smoking, regular prenatal care, inborn status, and maximum Finnegan score prior to MSO4 treatment. CONCLUSION: Use of PHF failed to impact short-term outcomes in infants treated for NAS including maximum MSO4 dose, duration of MSO4 treatment, and length of hospital stay. A prospective randomized controlled trial may be indicated to confirm this finding.

Reduced-Intensity Conditioning with Fludarabine, Melphalan, and Total Body Irradiation for Allogeneic Hematopoietic Cell Transplantation: The Effect of Increasing Melphalan Dose on Underlying Disease and Toxicity.

Disease relapse and toxicity are the shortcomings of reduced-intensity conditioning (RIC) for allogeneic hematopoietic cell transplantation (alloHCT). We hypothesized that adding total body irradiation (TBI) to and decreasing melphalan (Mel) from a base RIC regimen of fludarabine (Flu) and Mel would increase cytoreduction and improve disease control while decreasing toxicity. We performed a phase II trial of Flu 160 mg/m2, Mel 50 mg/m2, and TBI 400 cGy (FluMelTBI-50, n = 61), followed by a second phase II trial of Flu 160 mg/m2, Mel 75 mg/m2, and TBI 400cGy (FluMelTBI-75, n = 94) as RIC for alloHCT. Outcomes were compared with a contemporaneous cohort of 162 patients who received Flu 125 mg/m2 and Mel 140 mg/m2. Eligibility criteria were equivalent for all 3 regimens. All patients were ineligible for myeloablative/intensive conditioning. The median (range) follow-up for all patients was 51 (15 to 103) months. Day 100 donor lymphoid chimerism and transplant-related mortality, neutrophil and platelet engraftment, acute and chronic graft versus host disease incidence, overall survival (OS), and progression-free survival (PFS) were equivalent between FluMel, FluMelTBI-50, and FluMelTBI-75. Stomatitis wasdecreased for FluMelTBI versus FluMel (P < .01). PFS for patients not in complete remission on alloHCT was improved for FluMelTBI-75 versus FluMel (P = .03). On multivariate analysis, OS (P = .05) and PFS (P = .05) were significantly improved for FluMelTBI-75 versus FluMel. FluMelTBI-75 is better tolerated than FluMel, with improved survival and disease control.