Single-cell CAR T atlas reveals type 2 function in 8-year leukaemia remission.

Despite a high response rate in chimeric antigen receptor (CAR) T cell therapy for acute lymphocytic leukaemia (ALL)1-3, approximately 50% of patients relapse within the first year4-6, representing an urgent question to address in the next stage of cellular immunotherapy. Here, to investigate the molecular determinants of ultralong CAR T cell persistence, we obtained a single-cell multi-omics atlas from 695,819 pre-infusion CAR T cells at the basal level or after CAR-specific stimulation from 82 paediatric patients with ALL enrolled in the first two CAR T ALL clinical trials and 6 healthy donors. We identified that elevated type 2 functionality in CAR T infusion products is significantly associated with patients maintaining a median B cell aplasia duration of 8.4 years. Analysis of ligand-receptor interactions revealed that type 2 cells regulate a dysfunctional subset to maintain whole-population homeostasis, and the addition of IL-4 during antigen-specific activation alleviates CAR T cell dysfunction while enhancing fitness at both transcriptomic and epigenomic levels. Serial proteomic profiling of sera after treatment revealed a higher level of circulating type 2 cytokines in 5-year or 8-year relapse-free responders. In a leukaemic mouse model, type 2high CAR T cell products demonstrated superior expansion and antitumour activity, particularly after leukaemia rechallenge. Restoring antitumour efficacy in type 2low CAR T cells was attainable by enhancing their type 2 functionality, either through incorporating IL-4 into the manufacturing process or by priming manufactured CAR T products with IL-4 before infusion. Our findings provide insights into the mediators of durable CAR T therapy response and suggest potential therapeutic strategies to sustain long-term remission by boosting type 2 functionality in CAR T cells.

Exploring the Nature of Arhopalus ferus (Coleoptera: Cerambycidae: Spondylidinae) Pheromone Attraction.

Cerambycid species of the Spondylidinae subfamily are distributed worldwide and are known for being prolific invaders that infest conifers. In New Zealand, Arhopalus ferus (Mulsant), the burnt pine longhorn beetle, is well-established and requires monitoring at high-risk sites such as ports, airports, and sawmills as part of the requirements to meet pine log export standards set by the New Zealand Ministry of Primary Industries (MPI). Currently, its surveillance relies on traps baited with host volatiles (i.e., ethanol and α-pinene). We used volatile collections from adult beetles, electroantennograms, and field trapping bioassays to identify the pheromones emitted by the burnt pine longhorn beetle A. ferus and their effects on its behaviour. We show that A. ferus males emit mainly (E)-fuscumol and geranylacetone, as well as the minor components, α-terpinene and p-mentha-1,3,8-triene, and that all four compounds elicit a dose-dependent response in antennae of both sexes. Traps baited with the binary combination of geranylacetone plus fuscumol captured significantly more female A. ferus than did unbaited traps in two of three field experiments. α-Terpinene did not affect A. ferus trap catches and effects of p-mentha-1,3,8-triene on trap catch were not determined. Our findings provide further evidence of the use of fuscumol and geranylacetone as aggregation-sex pheromones by longhorn beetles in the Spondylidinae subfamily, and suggest that their deployment in survey traps may improve the efficacy of A. ferus monitoring in New Zealand and elsewhere.

Can adult polygenic scores improve prediction of body mass index in childhood?

BACKGROUND/OBJECTIVES: Modelling genetic pre-disposition may identify children at risk of obesity. However, most polygenic scores (PGSs) have been derived in adults, and lack validation during childhood. This study compared the utility of existing large-scale adult-derived PGSs to predict common anthropometric traits (body mass index (BMI), waist circumference, and body fat) in children and adults, and examined whether childhood BMI prediction could be improved by combining PGSs and non-genetic factors (maternal and earlier child BMI). SUBJECTS/METHODS: Participants (n = 1365 children, and n = 2094 adults made up of their parents) were drawn from the Longitudinal Study of Australian Children. Children were weighed and measured every two years from 0-1 to 12-13 years, and adults were measured or self-reported measurements were obtained concurrently (average analysed). Participants were genotyped from blood or oral samples, and PGSs were derived based on published genome-wide association studies. We used linear regression to compare the relative utility of these PGSs to predict their respective traits at different ages. RESULTS: BMI PGSs explained up to 12% of child BMI z-score variance in 10-13 year olds, compared with up to 15% in adults. PGSs for waist circumference and body fat explained less variance (up to 8%). An interaction between BMI PGSs and puberty (p = 0.001-0.002) suggests the effect of some variants may differ across the life course. Individual BMI measures across childhood predicted 10-60% of the variance in BMI at 12-13 years, and maternal BMI and BMI PGS each added 1-9% above this. CONCLUSION: Adult-derived PGSs for BMI, particularly those derived by modelling between-variant interactions, may be useful for predicting BMI during adolescence with similar accuracy to that obtained in adulthood. The level of precision presented here to predict BMI during childhood may be relevant to public health, but is likely to be less useful for individual clinical purposes.

Does an inflammatory diet affect mental well-being in late childhood and mid-life? A cross-sectional study.

Inflammatory diets are increasingly recognised as a modifiable determinant of mental illness. However, there is a dearth of studies in early life and across the full mental well-being spectrum (mental illness to positive well-being) at the population level. This is a critical gap given that inflammatory diet patterns and mental well-being trajectories typically establish by adolescence. We examined the associations of inflammatory diet scores with mental well-being in 11-12-year-olds and mid-life adults. Throughout Australia, 1759 11-12-year-olds (49 % girls) and 1812 parents (88 % mothers) contributed cross-sectional population-based data. Alternate inflammatory diet scores were calculated from a twenty-six-item FFQ, based on the prior literature and prediction of inflammatory markers. Participants reported negatively and positively framed mental well-being via psychosocial health, quality of life and life satisfaction surveys. We used causal inference modelling techniques via generalised linear regression models (mean differences and risk ratios (RR)) to examine how inflammatory diets might influence mental well-being. In children and adults, respectively, a 1 sd higher literature-derived inflammatory diet score conferred between a 44 % (RR 95 % CI 1·2, 1·8) to 57 % (RR 95 % CI 1·3, 2·0) and 54 % (95 % CI 1·2, 2·0) to 86 % (RR 95 % CI 1·4, 2·4) higher risk of being in the worst mental well-being category (i.e. <16th percentile) across outcome measures. Results for inflammation-derived scores were similar. BMI mediated effects (21-39 %) in adults. Inflammatory diet patterns were cross-sectionally associated with mental well-being at age 11-12 years, with similar effects observed in mid-adulthood. Reducing inflammatory dietary components in childhood could improve population-level mental well-being across the life course.

Diet quality trajectories and cardiovascular phenotypes/metabolic syndrome risk by 11-12 years.

OBJECTIVE: To investigate associations between early-life diet trajectories and preclinical cardiovascular phenotypes and metabolic risk by age 12 years. METHODS: Participants were 1861 children (51% male) from the Longitudinal Study of Australian Children. At five biennial waves from 2-3 to 10-11 years: Every 2 years from 2006 to 2014, diet quality scores were collected from brief 24-h parent/self-reported dietary recalls and then classified using group-based trajectory modeling as 'never healthy' (7%), 'becoming less healthy' (17%), 'moderately healthy' (21%), and 'always healthy' (56%). At 11-12 years: During children's physical health Child Health CheckPoint (2015-2016), we measured cardiovascular functional (resting heart rate, blood pressure, pulse wave velocity, carotid elasticity/distensibility) and structural (carotid intima-media thickness, retinal microvasculature) phenotypes, and metabolic risk score (composite of body mass index z-score, systolic blood pressure, high-density lipoproteins cholesterol, triglycerides, and glucose). Associations were estimated using linear regression models (n = 1100-1800) adjusted for age, sex, and socioeconomic position. RESULTS: Compared to 'always healthy', the 'never healthy' trajectory had higher resting heart rate (2.6 bpm, 95% CI 0.4, 4.7) and metabolic risk score (0.23, 95% CI 0.01, 0.45), and lower arterial elasticity (-0.3% per 10 mmHg, 95% CI -0.6, -0.1) and distensibility (-1.2%, 95% CI -1.9, -0.5) (all effect sizes 0.3-0.4). Heart rate, distensibility, and diastolic blood pressure were progressively poorer for less healthy diet trajectories (linear trends p ≤ 0.02). Effects for systolic blood pressure, pulse wave velocity, and structural phenotypes were less evident. CONCLUSIONS: Children following the least healthy diet trajectory had poorer functional cardiovascular phenotypes and metabolic syndrome risk, including higher resting heart rate, one of the strongest precursors of all-cause mortality. Structural phenotypes were not associated with diet trajectories, suggesting the window to prevent permanent changes remains open to at least late childhood.

Backyard benefits? A cross-sectional study of yard size and greenness and children's physical activity and outdoor play.

BACKGROUND: The home environment is the most important location in young children's lives, yet few studies have examined the relationship between the outdoor home environment and child physical activity levels, and even fewer have used objectively measured exposures and outcomes. This study examined relationships between objectively assessed home yard size and greenness, and child physical activity and outdoor play. METHODS: Data were drawn from the HealthNuts study, a longitudinal study of 5276 children in Melbourne, Australia. We used cross-sectional data from a sample at Wave 3 (2013-2016) when participants were aged 6 years (n = 1648). A sub-sample of 391 children had valid accelerometer data collected from Tri-axial GENEActive accelerometers worn on their non-dominant wrist for 8 consecutive days. Yard area and greenness were calculated using geographic information systems. Objective outcome measures were minutes/day in sedentary, light, and moderate-vigorous physical activity (weekday and weekend separately). Parent-reported outcome measures were minutes/day playing outdoors (weekend and weekday combined). Multi-level regression models (adjusted for child's sex, mother's age at the birth of child, neighbourhood socioeconomic index, maternal education, and maternal ethnicity) estimated effects of yard size and greenness on physical activity. RESULTS: Data were available on outdoor play for 1648 children and usable accelerometer data for 391. Associations between yard size/greenness and components of physical activity were minimal. For example, during weekdays, yard size was not associated with daily minutes in sedentary behaviour (ß: 2.4, 95% CI: - 6.2, 11.0), light physical activity (ß: 1.4, 95% CI: - 5.7, 8.5) or MVPA (ß: -2.4, 95% CI: - 6.5, 1.7), with similar patterns at weekends. There was no relationship between median annual yard greenness and physical activity or play. CONCLUSION: In our study of young children residing in higher socio-economic areas of Melbourne yard characteristics did not appear to have a major impact on children's physical activity. Larger studies with greater variation in yard characteristics and identification of activity location are needed to better understand the importance of home outdoor spaces and guide sustainable city planning.

A prospective multi-center quality improvement initiative (NINJA) indicates a reduction in nephrotoxic acute kidney injury in hospitalized children.

Nephrotoxic medication (NTMx) exposure is a common cause of acute kidney injury (AKI) in hospitalized children. The Nephrotoxic Injury Negated by Just-in time Action (NINJA) program decreased NTMx associated AKI (NTMx-AKI) by 62% at one center. To further test the program, we incorporated NINJA across nine centers with the goal of reducing NTMx exposure and, consequently, AKI rates across these centers. NINJA screens all non-critically ill hospitalized patients for high NTMx exposure (over three medications on the same day or an intravenous aminoglycoside over three consecutive days), and then recommends obtaining a daily serum creatinine level in exposed patients for the duration of, and two days after, exposure ending. Additionally, substitution of equally efficacious but less nephrotoxic medications for exposed patients starting the day of exposure was recommended when possible. The main outcome was AKI as defined by the Kidney Disease Improving Global Outcomes (KDIGO) serum creatinine criteria (increase of 50% or 0.3 mg/dl over baseline). The primary outcome measure was AKI episodes per 1000 patient-days. Improvement was defined by statistical process control methodology and confirmed by Autoregressive Integrated Moving Average (ARIMA) modeling. Eight consecutive bi-weekly measure rates in the same direction from the established baseline qualified as special cause change for special process control. We observed a significant and sustained 23.8% decrease in NTMx-AKI rates by statistical process control analysis and by ARIMA modeling; similar to those of the pilot single center. Thus, we have successfully applied the NINJA program to multiple pediatric institutions yielding decreased AKI rates.

Early clinical markers of overweight/obesity onset and resolution by adolescence.

OBJECTIVES: We examined how combinations of clinical indicators at various ages predict overweight/obesity development, as well as resolution, by 10-11 and 14-15 years of age. METHODS: Data were derived from Birth (N = 3469) and Kinder (N = 3276) cohorts of the Longitudinal Study of Australian Children, followed from ages 2-3 and 4-5 years, respectively. Every two years, 25 potential obesity-relevant clinical indicators were quantified. Overweight/obesity was defined using International Obesity Taskforce cutpoints at 10-11 years and 14-15 years. RESULTS: In both cohorts, three factors predicted both development and resolution of overweight/obesity in multivariable models. Among normal weight children, increased odds of developing overweight/obesity were associated with higher child (odd ratio (OR) 1.67-3.35 across different study waves) and maternal (OR 1.05-1.09) BMI, and inversely with higher maternal education (OR 0.60-0.62, when assessed at age 2-7 years). Lower odds of resolving existing overweight/obesity were related with higher child (OR 0.51-0.79) and maternal (OR 0.89-0.95) BMI, and inversely with higher maternal education (OR 1.62-1.92, when assessed at age 2-5 years). The prevalence of overweight/obesity at the age of 14-15 years was 13% among children with none of these risk factors at age 6-7 years, compared with 71% among those with all 3 risk factors (P < 0.001). CONCLUSIONS: From early childhood onwards, child and maternal BMI and maternal education predict overweight/obesity onset and resolution by adolescence. A simple risk score, easily available to child health clinicians, could help target treatment or prevention.

Do body mass index and waist-to-height ratio over the preceding decade predict retinal microvasculature in 11-12 year olds and midlife adults?

BACKGROUND/OBJECTIVES: Microvascular changes may contribute to obesity-associated cardiovascular disease. We examined whether body mass index (BMI) and waist-to-height ratio (WHtR) (1) at multiple earlier time points and (2) decade-long trajectories predicted retinal microvascular parameters in mid-childhood/adulthood. METHODS: Participants/design: 1288 11-12 year olds (51% girls) and 1264 parents (87% mothers) in the population-based Child Health CheckPoint (CheckPoint) module within the Longitudinal Study of Australian Children (LSAC). LSAC exposure measures: biennial BMI z-score and WHtR for children at five time points from age 2-3 to 10-11 years and self-reported parent BMI at six time points from child age 0-1 years to 10-11 years. CheckPoint outcome measures: retinal arteriolar and venular caliber. ANALYSES: BMI/WHtR trajectories were identified by group-based trajectory modeling; linear regression models estimated associations between BMI/WHtR at each time point/trajectories and later retinal vascular caliber, adjusted for age, sex, and family socioeconomic status. RESULTS: In time point analyses, higher child BMI/WHtR from age 4 to 5 years was associated with narrower arteriolar caliber at the age of 11-12 years, but not venular caliber. For example, each standard deviation higher in BMI z-score at 4-5 years was associated with narrower arteriolar caliber at 11-12 years (standardized mean difference (SMD): -0.05, 95% confidence interval (CI): -0.10 to 0.01); by 10-11 years, associations had doubled to -0.10 (95% CI: -0.16 to -0.05). In adults, these finding were similar, except the magnitude of BMI and arteriolar associations were similar across all time points (SMD: -0.11 to -0.13). In child and adult BMI trajectory analyses, less favorable trajectories predicted narrower arteriolar (p-trend < 0.05), but not venular (p-trend > 0.1), caliber. Compared with those in the average BMI trajectory, SMDs in arterial caliber for children and adults in the highest trajectory were -0.25 (95% CI: -0.44 to -0.07) and -0.42 (95% CI: -0.73 to -0.10), respectively. Venular caliber showed late associations with child WHtR, but not with BMI in children or adults. CONCLUSIONS: Associations of decade-long high BMI trajectories with narrowed retinal arteriolar caliber emerge in children, and are clearly evident by midlife. Adiposity appears to exert its early adverse life course impacts on the microcirculation more via arteriolar than venular mechanisms.

Cardiovascular health and retinal microvascular geometry in Australian 11-12 year-olds.

Traditional retinal microvascular parameters (smaller arteriolar and greater venular caliber) are associated with cardiovascular risk factors, pre-clinical vascular phenotypes and clinical cardiovascular events in adults. Although novel retinal microvascular geometric parameters showed analogous associations in adults, less is known whether these parameters are associated with cardiovascular health from childhood. In a population-based cross-sectional study in children (n = 1126, mean age 11.4 years, 50.3% girls), we examined associations of cardiovascular risk factors and pre-clinical arterial phenotypes with retinal geometric parameters. Cardiovascular parameters included body mass index (BMI), an inflammatory marker (GlycA), low-density lipoprotein and high-density lipoprotein (HDL) cholesterol, systolic (SBP) and diastolic blood pressure, large artery functional (pulse wave velocity, PWV and carotid arterial elasticity) and structural (carotid intima-media thickness) phenotypes. Retinal geometric parameters (fractal dimension (Df) and tortuosity) were quantified from retinal images. Multivariable regression models were performed and adjusted for potential confounders. Higher values for BMI, SBP and PWV showed weak associations with lower (i.e. worse) arteriolar but not venular Df (standardized mean difference (SMD) ranging from -0.07 to -0.09, 95% CIs -0.15 to -0.01). Higher HDL was associated with greater arteriolar Df (SMD 0.07, 95% CI 0.01 to 0.13). Only higher SBP was associated with higher (i.e. worse) arteriolar but not venular tortuosity (SMD 0.09, 95% CI 0.02 to 0.16). In generally healthy children, some risk factors and pre-clinical arterial phenotypes show small associations with retinal geometric parameters. In childhood, emerging relationships between microvascular parameters and cardiometabolic risk may be better described by retinal vascular caliber than by geometric parameters.

Light-Weight Portable Electroantennography Device as a Future Field-Based Tool for Applied Chemical Ecology.

Portable electroantennograms (pEAG) can further our understanding of odor plume dynamics and complement laboratory-based electroantennogram tools. pEAG's can help to address important questions such as the influence of plume structure on insect behavior, the active space of semiochemical-baited traps, and the impact of biotic and abiotic factors on this active space. Challenges associated with pEAGs include their miniaturization and sensitivity, confounding environmental odors, and processing of data. Here, we describe a pEAG built with modern engineering hardware and techniques that is portable in being both light in weight (516 g) and smaller (12 × 12 × 8 cm, volume 1152 cm3) than earlier models. It is able to incorporate insects of a range of sizes (4 to 30 mm antennal length), has wireless communication (communication range of 600 m urban, 10 km line of sight), a stand-alone power supply, and uses both antennae of the test insect. We report normalized antennal responses from Epiphyas postvittana in a dose response experiment where our pEAG compared favorably with traditional laboratory EAG equipment for this species. Dose-response comparisons between E. postvittana, Agrotis ipsilon, and Lymantria dispar dispar showed mean detection limits from a pheromone source dose of 100, 100, and 1 ng, respectively, for our pEAG. This pEAG should allow future real-time analysis of EAG responses in the field in research on how insects interact with odor plumes and the factors that influence the active space of semiochemical-baited traps.

Child and adult snack food intake in response to manipulated pre-packaged snack item quantity/variety and snack box size: a population-based randomized trial.

OBJECTIVES: Snacks contribute to overconsumption of energy-dense foods and thence obesity. Previous studies in this area are limited by self-reported data and small samples. In a large population-based cohort of parent-child dyads, we investigated how modification of pre-packaged snack food, i.e. (a) item quantity and variety, and (b) dishware (boxed container) size affected intake. METHODS: Design: Randomized trial nested within the cross-sectional Child Health CheckPoint of the Longitudinal Study of Australian Children, clustered by day of visit. SAMPLE: 1299 11-12 year olds, 1274 parents. EXPOSURE: 2 × 2 manipulation of snack box container size and item quantity/variety: (1) small box, few items, (2) large box, few items, (3) small box, more items, (4) large box, more items. PROCEDURE: Participants received a snack box during a 15 min break within their 3.5 h visit; any snacks remaining were weighed. OUTCOMES: Consumed quantity (grams) and energy intake (kilojoules). ANALYSES: Unadjusted linear regression. RESULTS: Children who were offered a greater quantity and variety of snack items consumed considerably more energy and a slightly higher food mass (main effect for energy intake: 349 kJ, 95% CI 282-416, standardized mean difference (effect size) 0.66; main effect for mass: 10 g, 95% CI 3-17, effect size 0.17). In contrast, manipulating box size had little effect on child consumption, and neither box size nor quantity/variety of items consistently affected adults' consumption. CONCLUSION: In children, reducing the number and variety of snack food items available may be a more fruitful intervention than focusing on container or dishware size. Effects observed among adults were small, although we could not exclude social desirability bias in adults aware of observation.

Bidirectional associations between diet and body composition measures from 2 to 15 years: Longitudinal Study of Australian Children.

This study investigates how dietary patterns and scores are associated with subsequent BMI and waist:height ratio (WHtR), and how BMI and WHtR are associated with subsequent dietary patterns or scores, from 2-3 to 10-11 and 4-5 to 14-15 years of age. In the Longitudinal Study of Australian Children, height, weight and waist circumference were measured biennially in children, yielding BMI z-score and WHtR. Parents, latterly children, reported frequency of child consumption of 12-16 food/drink items during the previous 24 h. At each wave, we empirically derived dietary patterns using factor analyses, and dietary scores based on the 2013 Australian Dietary Guidelines. We used structural-equation modelling to investigate cross-lagged associations (n 1972-2882) between diet and body composition measures in univariable and multivariable analyses. Dietary scores/patterns did not consistently predict WHtR and BMI z-score in the next wave, nor did BMI z-score and WHtR consistently predict diet in the next wave. The few associations seen were weak and often in the opposite direction to that hypothesised. The largest effect, associated with each standard deviation increase in BMI in wave 5 of the K cohort (age 12-13 years), was a 0·06 standard deviation estimated mean increase in dietary score (higher quality diet) in the subsequent wave (95 % CI 0·02, 0·11, P=0·003). Associations between dietary patterns/scores and body composition were not strongly evident in either direction. Better quantitative childhood dietary tools feasible for large-scale administration are needed to quantify how dietary patterns, energy intake and anthropometry co-develop.

Eating disorder symptoms across the weight spectrum in Australian adolescents.

OBJECTIVE: Despite known associations between eating disorders and obesity, little is known about the current prevalence of symptoms of eating disorders across the weight spectrum. This study therefore aimed to estimate the population prevalence of eating disorder symptoms in relation to weight status in adolescents. METHOD: The sample comprised 3,270 participants (14-15 years; 52% boys) drawn from Wave 6 of the Longitudinal Study of Australian Children. Symptoms of anorexia nervosa (AN) and bulimia nervosa (BN) were assessed using self-report on the Branched Eating Disorder Test. This measure identifies clinically significant symptoms in the past 3 months according to the Diagnostic and Statistical Manual of Mental Disorders, fifth edition. Using study-derived cross-sectional population weights, the prevalence of each symptom was estimated for the total population and by sex and weight status. RESULTS: The estimated population prevalence was high (14.3-25.7%) for body image symptoms such as fear of weight gain and overvaluation of body weight but lower (0.5-3.7%) for behavioral symptoms such as binge eating and compensatory behaviors. Symptoms were more prevalent among adolescents with overweight or obesity. Although most symptoms tended to have higher prevalence among girls than boys, boys with obesity had higher prevalence of binge eating and excessive exercise than girls with obesity. The overall estimated population prevalence for AN and BN was 0.20% and 0.10%, respectively. DISCUSSION: The study highlights a need for clinicians to be cognizant of disordered eating behaviors regardless of weight status and has implications for both eating disorder and obesity prevention and intervention.

Fostering interprofessional teamwork through an immersive study abroad experience.

In 2017, American university students representing seven healthcare professions traveled to Australia (AU) for a 17-day study abroad course focused on expanding students' knowledge of interprofessional education (IPE) and global communities. This innovative course allowed for an immersive IPE learning experience through an examination of healthcare and culture. Based upon pilot study survey data from the 12 participating students (i.e., students from athletic training, nursing, occupational therapy, physical therapy, physician assistant studies, pre-medical, and speech-language pathology), positive perceptions of the experience related to teamwork, learning, and healthcare differences were achieved. However, survey data from the Readiness for Interprofessional Learning Scale (RIPLS) showed no significant change in attitudes or perceptions of collaboration, professional identity, or roles and responsibilities. These results suggest the potential that students who elect to participate in optional IPE study abroad programs already have positive attitudes toward IPE. Study abroad may be an appropriate setting to expand healthcare students' appreciation of IPE, teamwork, and global awareness. The results of this study may assist other professionals in developing future IPE activities in the international setting.

Preoperative Evaluation Is Not Predictive of Transpyloric Feeding Conversion in Gastrostomy-dependent Pediatric Patients.

OBJECTIVES: Limited literature exists as to whether preoperative gastrostomy (GT) evaluation may predict which patients will go onto require gastrojejunostomy (GJ) tube feeding. The goal of this study was to compare the preoperative evaluations between patients maintained on GT feeds versus patients who required conversion to GJ feeds. METHODS: We identified patients at Boston Children's Hospital who underwent GT tube placement and required GJ feeding between 2006 and 2012. GT patients were matched according to age, neurologic, and cardiac status with GJ-converted patients. Preoperative characteristics, rates of total hospitalizations, and respiratory-related admissions were reviewed. RESULTS: A total of 79 GJ patients (median interquartile range (IQR): age 15 (4.3, 55.7) months; weight 8.8 (4.6, 14.5) kg) were matched with 79 GT patients (median (IQR): age 14.6 (4.7, 55.7) months; weight 8.5 (5, 13.6) kg). Median time from GT to GJ conversion was 8 (IQR 3, 16) months. Both groups had similar rates of successful preoperative nasogastric feeding trials (GT (84.5%) versus GJ (83.1%), P = 1.0), upper gastrointestinal series (GT (89.1%) versus GJ (93.2%), P = 0.73), abnormal videofluoroscopic swallow studies (GT (53.8%) versus GJ (62.2%), P = 0.4), and completion of gastric emptying studies (GT (10.1%) versus GJ (5.1%), P = 0.22). No differences were seen in preoperative hospitalization rates (P = 0.25), respiratory admissions (P = 0.36), although GJ patients had a mean reduction in the number of hospitalization of -1.5 ±â€Š0.5 days, P < 0.001, after conversion. CONCLUSIONS: No differences in preoperative patient characteristics or diagnostic evaluations were seen in GT fed versus GJ converted patients. GJ patients did experience an overall decrease in total admissions after GJ conversion.

Parental health behaviour predictors of childhood and adolescent dietary trajectories.

OBJECTIVE: To determine which parental health behaviours early in childhood most strongly predict whole-of-childhood dietary trajectories. DESIGN: Population-based Longitudinal Study of Australian Children (LSAC, waves 1-6; 2004-2014). Exposures were parents' fruit/vegetable consumption, alcohol, smoking and physical activity at child age 0-1 years (B Cohort) or 4-5 years (K Cohort). Outcomes, from repeated biennial short diet diaries, were group-based trajectories of (i) dietary scores and empirically derived patterns of (ii) healthful and (iii) unhealthful foods consumed, spanning ages 2-3 to 10-11 years (B Cohort) and 4-5 to 14-15 years (K Cohort). We investigated associations of baseline parental health behaviours with child dietary trajectories using multinomial logistic regression. SETTING: Australian homes. SUBJECTS: Of children, 4443 (87·0 %) from the B Cohort and 4620 (92·7 %) from the K Cohort were included in all trajectories. Multivariable analyses included 2719 to 2905 children and both parents. RESULTS: Children whose primary caregiver reported the lowest fruit/vegetable consumption had markedly higher odds of belonging to the least healthy score and pattern trajectories (K Cohort: OR=8·7, 95 % CI 5·0, 15·1 and OR=8·4, 95 % CI 4·8, 14·7, respectively); associations were weaker (K Cohort: OR=2·3, 95 % CI 1·0, 5·2) for the unhealthiest pattern trajectory. Secondary caregiver fruit/vegetable associations were smaller and inconsistent. Parental alcohol, smoking and physical activity were not predictive in multivariable analyses. Results were largely replicated for the B Cohort. CONCLUSIONS: Low primary caregiver fruit/vegetable consumption increased nearly ninefold the odds of children being in the lowest intake of healthy, but only weakly predicted unhealthy, food trajectories. Healthy and unhealthy food intake may have different determinants.

Childhood dietary trajectories and adolescent cardiovascular phenotypes: Australian community-based longitudinal study.

OBJECTIVE: With the intention to inform future public health initiatives, we aimed to determine the extent to which typical childhood dietary trajectories predict adolescent cardiovascular phenotypes. DESIGN: Longitudinal study. Exposure was determined by a 4 d food diary repeated over eight waves (ages 4-15 years), coded by Australian Dietary Guidelines and summed into a continuous diet score (0-14). Outcomes were adolescent (Wave 8, age 15 years) blood pressure, resting heart rate, pulse wave velocity, carotid intima-media thickness, retinal arteriole-to-venule ratio. Latent class analysis identified 'typical' dietary trajectories from childhood to adolescence. Adjusted linear regression models assessed relationships between trajectories and cardiovascular outcomes, adjusted for a priori potential confounders. SETTING: Community sample, Melbourne, Australia. SUBJECTS: Children (n 188) followed from age 4 to 15 years. RESULTS: Four dietary trajectories were identified: unhealthy (8 %); moderately unhealthy (25 %); moderately healthy (46 %); healthy (21 %). There was little evidence that vascular phenotypes associated with the trajectories. However, resting heart rate (beats/min) increased (ß; 95 % CI) across the healthy (reference), moderately healthy (4·1; -0·6, 8·9; P=0·08), moderately unhealthy (4·5; -0·7, 9·7; P=0·09) and unhealthy (10·5; 2·9, 18·0; P=0·01) trajectories. CONCLUSIONS: Decade-long dietary trajectories did not appear to influence macro- or microvascular structure or stiffness by mid-adolescence, but were associated with resting heart rate, suggesting an early-life window for prevention. Larger studies are needed to confirm these findings, the threshold of diet quality associated with these physiological changes and whether functional changes in heart rate are followed by phenotypic change.

Associations of mental health with cardiovascular risk phenotypes and adiposity in adolescence: A cross-sectional community-based study.

AIM: Cardiovascular disease and mental illness commonly co-occur in later life, but it is unknown how early these associations arise. We aimed to determine the extent to which: (i) childhood mental health is associated with functional and structural cardiovascular risk phenotypes and adiposity in late childhood/adolescence, and (ii) associations between mental health and cardiovascular phenotypes may be explained by differential body mass index. METHODS: This cross-sectional study drew on three longitudinal community-based cohort studies (two enriched for overweight/obesity) in metropolitan Melbourne, Australia, with harmonized follow-up in 2014. Mental health exposures included emotional and behavioural problems (Strength and Difficulties Questionnaire) and psychosocial health and general well-being (Pediatric Quality of Life Inventory (PedsQL)), which were assessed by self- and parent-proxy report. Cardiovascular risk phenotypes and adiposity measures included mean arterial pressure, pulse wave velocity, carotid artery intima-media thickness, retinal arterioleto-venule ratio, waist circumference, % body fat, and BMI z-score. We used multivariable linear regression models, adjusting for age, sex and neighbourhood disadvantage, to examine associations. RESULTS: Of the 364 participants (mean age 14.7, standard deviation 2.0, years), 30% were overweight and 16% obese. All adiposity indicators were positively associated with higher behavioural/emotional problems and poorer psychosocial health and negatively associated with better ratings of positive general well-being, as reported by parents and children (all P ≤ 0.03). However, there was little evidence that cardiovascular functional or structural phenotypes varied by mental health. CONCLUSIONS: By late childhood/adolescence, mental health is strongly associated with adiposity but not with cardiovascular structure or function. This suggests that the known relationship between these constructs may not develop until early or mid-adulthood.

Monitoring Patients on Metformin: Recent Changes and Rationales.

Objective: The Food and Drug Administration recently updated metformin prescribing recommendations for patients with diabetes and renal disease. The American Diabetes Association as well as the American Association of Clinical Endocrinologists and American Clinical Endocrinologists also recommend periodic monitoring of vitamin B12 levels for patients using metformin. A review of the literature was conducted to assess data to evaluate the recent updates to metformin usage and provide rationales for these recommendations. Data Sources: PubMed MESH terms "Diabetes Mellitus, Type 2" and "Renal Insufficiency, Chronic" and "Metformin" were searched with an English limitation from 1990 to May 2017. A MEDLINE search was conducted using the terms "metformin" and "renal disease" from 1990 to May 2017. A PubMed search was conducted using the MESH terms "vitamin b12 deficiency" and "metformin" from 1970 to May 2017. A MEDLINE search was conducted using terms "metformin" and "vitamin B12 deficiency" with an English limitation from 1970 to May 2017. Study Selection and Data Extraction: Retrospective and prospective clinical trials, meta-analyses, and systematic reviews were considered for inclusion. Citations from identified articles were also reviewed for inclusion. Data Synthesis: The incidence of metformin-associated lactic acidosis is minimal. Data indicate metformin-treated patients with an estimated glomerular filtration rate above 30 mL/min/1.73 m2 have a reduction in mortality. Additionally, data suggest metformin may lead to vitamin B12 deficiency. Conclusion: Data support recommendations for metformin use in patients with diabetes and renal insufficiency with an estimated glomerular filtration rate above 30 mL/min/1.73 m2. Data also suggest that baseline and periodic testing of vitamin B12 levels are warranted and supported by clinical guidelines due to the risk of vitamin B12 deficiency in metformin-treated patients.