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Abstract Background A low-fat vegan diet, supplemented with soybeans, has been shown effective in reducing postmenopausal hot flashes. This secondary analysis assessed the association of a plant-based index (PDI), healthful (hPDI), and unhealthful (uPDI), with changes in hot flashes in postmenopausal women. Methods Participants (n = 84) were randomly assigned to a low-fat vegan diet supplemented with soybeans (n = 42) or a control group (n = 42) for 12 weeks. Three-day dietary records were analyzed and PDI indices were calculated. A repeated measures analysis of variance (ANOVA) was used for statistical analysis. Results All three scores increased in the vegan group, compared with no change in the control group; the effect sizes were: PDI + 9.8 (95% CI + 5.8 to + 13.8; p

ObjectiveEvidence suggests that changes in dietary advanced glycation end-products (AGEs) may influence body weight, but the effects of different dietary patterns remain to be explored.The aim of this study was to compare the effects of a Mediterranean and a low-fat vegan diet on dietary AGEs and test their association with body weight.Materials and methodsIn this randomized cross-over trial, 62 overweight adults were assigned to a Mediterranean or a low-fat vegan diet for 16-week periods in random order, separated by a 4-week washout. Body weight was the primary outcome. Three-day diet records were analyzed using the Nutrition Data System for Research software and dietary AGEs were estimated, using an established database. Statistical approaches appropriate for crossover trials were implemented.ResultsDietary AGEs decreased by 73%, that is, by 9,413 kilounits AGE/day (95% −10,869 to −7,957); p < 0.001, compared with no change on the Mediterranean diet (treatment effect −10,303 kilounits AGE/day [95% CI −13,090 to −7,516]; p < 0.001). The participants lost 6.0 kg on average on the vegan diet, compared with no change on the Mediterranean diet (treatment effect −6.0 kg [95% CI −7.5 to −4.5]; p < 0.001). Changes in dietary AGEs correlated with changes in body weight (r = +0.47; p < 0.001) and remained significant after adjustment for total energy intake (r = +0.39; p = 0.003).ConclusionDietary AGEs did not change on the Mediterranean diet but decreased on a low-fat vegan diet, and this decrease was associated with changes in body weight, independent of energy intake.Clinical trial registrationhttps://clinicaltrials.gov/, identifier NCT03698955

Abstract Background Intensive care unit (ICU) patients on mechanical ventilation often require sedation and analgesia to improve comfort and decrease pain. Prolonged sedation and analgesia, however, may increase time on mechanical ventilation, risk for ventilator associated pneumonia, and delirium. Coordinated interruptions in sedation [spontaneous awakening trials (SATs)] and spontaneous breathing trials (SBTs) increase ventilator-free days and improve mortality. Coordination of SATs and SBTs is difficult with substantial implementation barriers due to difficult-to-execute sequencing between nurses and respiratory therapists. Telehealth-enabled remote care has the potential to overcome these barriers and improve coordinated SAT and SBT adherence by enabling proactive high-risk patient monitoring, surveillance, and real-time assistance to frontline ICU teams. Methods The telehealth-enabled, real-time audit and feedback for clinician adherence (TEACH) study will determine whether adding a telehealth augmented real-time audit and feedback to a usual supervisor-led audit and feedback intervention will yield higher coordinated SAT and SBT adherence and more ventilator-free days in mechanically ventilated patients than a usual supervisor-led audit and feedback intervention alone in a type II hybrid effectiveness-implementation cluster-randomized clinical trial in 12 Intermountain Health hospitals with 15 ICUs. In the active comparator control group (six hospitals), the only intervention is the usual supervisor-led audit and feedback implementation. The telehealth-enabled support (TEACH) intervention in six hospitals adds real-time identification of patients eligible for a coordinated SAT and SBT and consultative input from telehealth respiratory therapists, nurses, and physicians to the bedside clinicians to promote adherence including real-time assistance with execution. All intubated and mechanically ventilated patients ≥ 16 years of age are eligible for enrollment except for patients who die on the day of intubation or have preexisting brain death. Based on preliminary power analyses, we plan a 36-month intervention period that includes a 90-day run-in period. Estimated enrollment in the final analysis is up to 9900 mechanically ventilated patients over 33 months. Discussion The TEACH study will enhance implementation science by providing insight into how a telehealth intervention augmenting a usual audit and feedback implementation may improve adherence to coordinated SAT and SBT and increase ventilator-free days. Trial registration Clinicaltrials.gov, NCT05141396 , registered 12/02/2021.

Abstract Background Evidence suggests that changes in advanced glycation end‐products (AGEs) may influence body weight. Previous studies have focused on cooking methods as the primary way how to reduce the dietary AGEs but little is known about the effects of a change in diet composition. Objective The aim of this study was to assess the effects of a low‐fat plant‐based diet on dietary AGEs and test the association with body weight, body composition, and insulin sensitivity. Methods Participants who were overweight (n = 244) were randomly assigned to an intervention (low‐fat plant‐based) (n = 122) or control group (n = 122) for 16 weeks. Before and after the intervention period, body composition was measured by dual X‐ray absorptiometry. Insulin sensitivity was assessed with the predicted insulin sensitivity index (PREDIM). Three‐day diet records were analyzed using the Nutrition Data System for Research software and dietary AGEs were estimated, using a database. Repeated measure ANOVA was used for statistical analysis. Results Dietary AGEs decreased in the intervention group by 8768 ku/day on average (95% −9611 to −7925; p

Objective: This study examined the role of gut microbiome changes in mediating the effects of a dietary intervention on the frequency and severity of postmenopausal vasomotor symptoms Methods: Postmenopausal women (n = 84) reporting ≥2 moderate-to-severe hot flashes daily were randomly assigned, in 2 successive cohorts, to an intervention including a low-fat, vegan diet and cooked soybeans (½ cup [86 g] daily) or to stay on their usual diet. Over a 12-week period, frequency and severity of hot flashes were recorded with a mobile application. In a subset of 11 women, gut microbiome was analyzed at baseline and after 12 weeks of the dietary intervention (low-fat vegan diet with soybeans), using deep shotgun metagenomic sequencing. Differences in the microbiome between baseline and 12 weeks were assessed by comparing alpha diversity with Wilcoxon signed rank tests, beta diversity with permanovaFL, and taxon abundance with Wilcoxon signed rank tests. Pearson correlations were used to assess the association between changes in hot flashes and gut bacteria. Results: In the subset for which microbiome testing was done, total hot flashes decreased by 95 % during the dietary intervention (p = 0.007); severe hot flashes disappeared (from 0.6 to 0.0/day; p = 0.06); and moderate-to-severe hot flashes decreased by 96 % (p = 0.01). Daytime and nighttime hot flashes were reduced by 96 % (p = 0.01) and 94 % (p = 0.004), respectively. Alpha and beta diversity did not significantly differ in the intervention group between baseline and 12 weeks. Two families (Enterobacteriaceae and Veillonellaceae), 5 genera (Erysipelatoclostridium, Fusicatenibacter, Holdemanella, Intestinimonas, and Porphyromonas), and 6 species (Clostridium asparagiforme, Clostridium innocuum, Bacteroides thetaiotaomicron, Fusicatenibacter saccharivorans, Intestinimonas butyriciproducens, Prevotella corporis, and Streptococcus sp.) were differentially abundant, but after correction for multiple comparisons, these differences were no longer significant. Changes in the relative abundance of Porphyromonas and Prevotella corporis were associated with the reduction in severe day hot flashes both unadjusted (r = 0.61; p = 0.047; and r = 0.69; p = 0.02), respectively), and after adjustment for changes in body mass index (r = 0.63; p = 0.049; and r = 0.73; p = 0.02), respectively). Changes in relative abundance of Clostridium asparagiforme were associated with the reduction in total severe hot flashes (r = 0.69; p = 0.019) and severe night hot flashes (r = 0.82; p = 0.002) and the latter association remained significant after adjustment for changes in body mass index (r = 0.75; p = 0.01). Conclusions: This exploratory analysis revealed potential associations between changes in vasomotor symptoms in response to a diet change and changes in the gut microbiome. Larger randomized clinical trials are needed to investigate these findings.

Abstract Background Thrombotic microangiopathy-induced thrombocytopenia-associated multiple organ failure and hyperinflammatory macrophage activation syndrome are important causes of late pediatric sepsis mortality that are often missed or have delayed diagnosis. The National Institutes of General Medical Science sepsis research working group recommendations call for application of new research approaches in extant clinical data sets to improve efficiency of early trials of new sepsis therapies. Our objective is to apply machine learning approaches to derive computable 24-h sepsis phenotypes to facilitate personalized enrollment in early anti-inflammatory trials targeting these conditions. Methods We applied consensus, k-means clustering analysis to our extant PHENOtyping sepsis-induced Multiple organ failure Study (PHENOMS) dataset of 404 children. 24-hour computable phenotypes are derived using 25 available bedside variables including C-reactive protein and ferritin. Results Four computable phenotypes (PedSep-A, B, C, and D) are derived. Compared to all other phenotypes, PedSep-A patients (n = 135; 2% mortality) were younger and previously healthy, with the lowest C-reactive protein and ferritin levels, the highest lymphocyte and platelet counts, highest heart rate, and lowest creatinine (p

Abstract Background Retaining participants over time is a frequent challenge in research studies evaluating long-term health outcomes. This study’s objective was to compare the impact of prepaid and postpaid incentives on response to a six-month follow-up survey. Methods We conducted an experiment to compare response between participants randomized to receive either prepaid or postpaid cash card incentives within a multisite study of children under 15 years in age who were hospitalized for a serious, severe, or critical injury. Participants were parents or guardians of enrolled children. The primary outcome was survey response. We also examined whether demographic characteristics were associated with response and if incentive timing influenced the relationship between demographic characteristics and response. We evaluated whether incentive timing was associated with the number of calls needed for contact. Results The study enrolled 427 children, and parents of 420 children were included in this analysis. Follow-up survey response did not differ according to the assigned treatment arm, with the percentage of parents responding to the survey being 68.1% for the prepaid incentive and 66.7% with the postpaid incentive. Likelihood of response varied by demographics. Spanish-speaking parents and parents with lower income and lower educational attainment were less likely to respond. Parents of Hispanic/Latino children and children with Medicaid insurance were also less likely to respond. We found no relationship between the assigned incentive treatment and the demographics of respondents compared to non-respondents. Conclusions Prepaid and postpaid incentives can obtain similar participation in longitudinal pediatric critical care outcomes research. Incentives alone do not ensure retention of all demographic subgroups. Strategies for improving representation of hard-to-reach populations are needed to address health disparities and ensure the generalizability of studies using these results.

Abstract Introduction Hospital readmission rates are an indicator of the health care quality provided by hospitals. Applying machine learning (ML) to a hospital readmission database offers the potential to identify patients at the highest risk for readmission. However, few studies applied ML methods to predict hospital readmission. This study sought to assess ML as a tool to develop prediction models for all-cause 90-day hospital readmission for dental patients. Methods Using the 2013 Nationwide Readmissions Database (NRD), the study identified 9260 cases for all-cause 90-day index admission for dental patients. Five ML classification algorithms including decision tree, logistic regression, support vector machine, k-nearest neighbors, and artificial neural network (ANN) were implemented to build predictive models. The model performance was estimated and compared by using area under the receiver operating characteristic curve (AUC), and accuracy, sensitivity, specificity, and precision. Results Hospital readmission within 90 days occurred in 1746 cases (18.9%). Total charges, number of diagnosis, age, number of chronic conditions, length of hospital stays, number of procedures, primary expected payer, and severity of illness emerged as the top eight important features in all-cause 90-day hospital readmission. All models had similar performance with ANN (AUC = 0.743) slightly outperforming the rest. Conclusion This study demonstrates a potential annual saving of over $500 million if all of the 90-day readmission cases could be prevented for 21 states represented in the NRD. Among the methods used, the prediction model built by ANN exhibited the best performance. Further testing using ANN and other methods can help to assess important readmission risk factors and to target interventions to those at the greatest risk.

Background: Although some pediatric sepsis survivors experience worsening health-related quality of life (HRQL), many return to their pre-illness HRQL. Whether children can improve beyond baseline is not known. We examined a cohort of pediatric sepsis survivors to determine if those with baseline HRQL scores below the population mean could exhibit ≥10% improvement and evaluated factors associated with improvement.Methods: In this secondary analysis of the Life After Pediatric Sepsis Evaluation prospective study, children aged 1 month to 18 years admitted to 12 academic PICUs in the United States with community-acquired septic shock who survived to 3 months and had baseline HRQL scores ≤ 80 (i.e., excluding those with good baseline HRQL to allow for potential improvement) were included. HRQL was measured using the Pediatric Quality of Life Inventory or Stein-Jessop Functional Status Scale.Findings: One hundred and seventeen children were eligible. Sixty-one (52%) had ≥ 10% improvement in HRQL by 3 months. Lower pre-sepsis HRQL was associated with increased odds of improvement at 3 months [aOR = 1.08, 95% CI (1.04–1.11), p < 0.001] and 12 months [OR = 1.05, 95% CI (1.02–1.11), p = 0.005]. Improvement in HRQL was most prevalent at 3 month follow-up; at 12 month follow-up, improvement was more sustained among children without severe developmental delay compared to children with severe developmental delay.Interpretation: More than half of these children with community acquired septic shock experienced at least a 10% improvement in HRQL from baseline to 3 months. Children with severe developmental delay did not sustain this improvement at 12 month follow-up.

Objective: To model pre-injury child and family factors associated with the trajectory of internalizing and externalizing behavior problems across the first 3 years in children with pediatric traumatic brain injury (TBI) relative to children with orthopedic injuries (OI). Parent-reported emotional symptoms and conduct problems were expected to have unique and shared predictors. We hypothesized that TBI, female sex, greater pre-injury executive dysfunction, adjustment problems, lower income, and family dysfunction would be associated with less favorable outcomes.Methods: In a prospective longitudinal cohort study, we examined the level of behavior problems at 12 months after injury and rate of change from pre-injury to 12 months and from 12 to 36 months in children ages 4–15 years with mild to severe TBI relative to children with OI. A structural equation model framework incorporated injury characteristics, child demographic variables, as well as pre-injury child reserve and family attributes. Internalizing and externalizing behavior problems were indexed using the parent-rated Emotional Symptoms and Conduct Problems scales from the Strengths and Difficulties questionnaire.Results: The analysis cohort of 534 children [64% boys, M (SD) 8.8 (4.3) years of age] included 395 with mild to severe TBI and 139 with OI. Behavior ratings were higher after TBI than OI but did not differ by TBI severity. TBI, higher pre-injury executive dysfunction, and lower income predicted the level and trajectory of both Emotional Symptoms and Conduct Problems at 12 months. Female sex and poorer family functioning were vulnerability factors associated with greater increase and change in Emotional Symptoms by 12 months after injury; unique predictors of Conduct Problems included younger age and prior emotional/behavioral problems. Across the long-term follow-up from 12 to 36 months, Emotional Symptoms increased significantly and Conduct Problems stabilized. TBI was not a significant predictor of change during the chronic stage of recovery.Conclusions: After TBI, Emotional Symptoms and Conduct Problem scores were elevated, had different trajectories of change, increased or stayed elevated from 12 to 36 months after TBI, and did not return to pre-injury levels across the 3 year follow-up. These findings highlight the importance of addressing behavioral problems after TBI across an extended time frame.

ObjectiveEfforts directed at mitigating neurological disability in preterm infants with intraventricular hemorrhage (IVH) and post hemorrhagic hydrocephalus (PHH) are limited by a dearth of quantifiable metrics capable of predicting long-term outcome. The objective of this study was to examine the relationships between candidate cerebrospinal fluid (CSF) biomarkers of PHH and neurodevelopmental outcomes in infants undergoing neurosurgical treatment for PHH.Study designPreterm infants with PHH were enrolled across the Hydrocephalus Clinical Research Network. CSF samples were collected at the time of temporizing neurosurgical procedure (n = 98). Amyloid precursor protein (APP), L1CAM, NCAM-1, and total protein (TP) were compared in PHH versus control CSF. Fifty-four of these PHH subjects underwent Bayley Scales of Infant Development-III (Bayley-III) testing at 15-30 months corrected age. Controlling for false discovery rate (FDR) and adjusting for post-menstrual age (PMA) and IVH grade, Pearson's partial correlation coefficients were used to examine relationships between CSF proteins and Bayley-III composite cognitive, language, and motor scores.ResultsCSF APP, L1CAM, NCAM-1, and TP were elevated in PHH over control at temporizing surgery. CSF NCAM-1 was associated with Bayley-III motor score (R = -0.422, p = 0.007, FDR Q = 0.089), with modest relationships noted with cognition (R = -0.335, p = 0.030, FDR Q = 0.182) and language (R = -0.314, p = 0.048, FDR Q = 0.194) scores. No relationships were observed between CSF APP, L1CAM, or TP and Bayley-III scores. FOHR at the time of temporization did not correlate with Bayley-III scores, though trends were observed with Bayley-III motor (p = 0.0647 and R = -0.2912) and cognitive scores (p = 0.0506 and R = -0.2966).ConclusionCSF NCAM-1 was associated with neurodevelopment in this multi-institutional PHH cohort. This is the first report relating a specific CSF protein, NCAM-1, to neurodevelopment in PHH. Future work will further investigate a possible role for NCAM-1 as a biomarker of PHH-associated neurological disability.

Abstract Background Quality of cardiopulmonary resuscitation (CPR) is associated with survival, but recommended guidelines are often not met, and less than half the children with an in-hospital arrest will survive to discharge. A single-center before-and-after study demonstrated that outcomes may be improved with a novel training program in which all pediatric intensive care unit staff are encouraged to participate in frequent CPR refresher training and regular, structured resuscitation debriefings focused on patient-centric physiology. Methods/design This ongoing trial will assess whether a program of structured debriefings and point-of-care bedside practice that emphasizes physiologic resuscitation targets improves the rate of survival to hospital discharge with favorable neurologic outcome in children receiving CPR in the intensive care unit. This study is designed as a hybrid stepped-wedge trial in which two of ten participating hospitals are randomly assigned to enroll in the intervention group and two are assigned to enroll in the control group for the duration of the trial. The remaining six hospitals enroll initially in the control group but will transition to enrolling in the intervention group at randomly assigned staggered times during the enrollment period. Discussion To our knowledge, this is the first implementation of a hybrid stepped-wedge design. It was chosen over a traditional stepped-wedge design because the resulting improvement in statistical power reduces the required enrollment by 9 months (14%). However, this design comes with additional challenges, including logistics of implementing an intervention prior to the start of enrollment. Nevertheless, if results from the single-center pilot are confirmed in this trial, it will have a profound effect on CPR training and quality improvement initiatives. Trial registration ClinicalTrials.gov, NCT02837497. Registered on July 19, 2016.

Atherosclerosis is the major cause of coronary artery disease (CAD), and oxidized LDL (oxLDL) is believed to play a key role in the initiation of the atherosclerotic process. Recent studies show that inflammation and autoimmune reactions are also relevant in atherosclerosis. In this study, we examined the association of antibodies against oxLDL (anti-oxLDL) with the severity of CAD in 558 Women's Ischemia Syndrome Evaluation (WISE) study samples (465 whites; 93 blacks) determined by coronary stenosis (50% stenosis). We also examined the relationship of anti-oxLDL with serum lipid levels and nine candidate genes including APOE, APOH, APOA5, LPL, LRP1, HL, CETP, PON1, and OLR1. IgM anti-oxLDL levels were significantly higher in the >20% stenosis group than in the ≥20% stenosis group in whites (0.69 ± 0.02 vs. 0.64 ± 0.01, respectively; P = 0.02). IgM anti-oxLDL levels correlated significantly with total cholesterol (r2= 0.01; P = 0.03) and LDL cholesterol (r2= 0.017; P = 0.004) in whites. Multiple regression analysis revealed a suggestive association of LPL/S447X single-nucleotide polymorphism (SNP) with both IgG anti-oxLDL (P = 0.02) and IgM anti-oxLDL (P = 0.07), as well as between IgM anti-oxLDL and the OLR1/3′UTR SNP (P = 0.020). Our data suggest that higher IgM anti-oxLDL levels may provide protection against coronary stenosis and that genetic variation in some candidate genes are determinants of anti-oxLDL levels.

Neurological outcomes of preterm infants with post-hemorrhagic hydrocephalus (PHH) remain among the worst in infancy, yet there remain few instruments to inform the treatment of PHH. We previously observed PHH-associated elevations in cerebrospinal fluid (CSF) amyloid precursor protein (APP), neural cell adhesion molecule-L1 (L1CAM), neural cell adhesion molecule-1 (NCAM-1), and other protein mediators of neurodevelopment.The objective of this study was to examine the association of CSF APP, L1CAM, and NCAM-1 with ventricular size as an early step toward developing CSF markers of PHH.CSF levels of APP, L1CAM, NCAM-1, and total protein (TP) were measured in 12 preterm infants undergoing PHH treatment. Ventricular size was determined using cranial ultrasounds. The relationships between CSF APP, L1CAM, and NCAM-1, occipitofrontal circumference (OFC), volume of CSF removed, and ventricular size were examined using correlation and regression analyses.CSF levels of APP, L1CAM, and NCAM-1 but not TP paralleled treatment-related changes in ventricular size. CSF APP demonstrated the strongest association with ventricular size, estimated by frontal-occipital horn ratio (FOR) (Pearson R = 0.76, p = 0.004), followed by NCAM-1 (R = 0.66, p = 0.02) and L1CAM (R = 0.57,p = 0.055). TP was not correlated with FOR (R = 0.02, p = 0.95).Herein, we report the novel observation that CSF APP shows a robust association with ventricular size in preterm infants treated for PHH. The results from this study suggest that CSF APP and related proteins at once hold promise as biomarkers of PHH and provide insight into the neurological consequences of PHH in the preterm infant.