Prolonged Enteral Tube Feeding in Infants With a Functional Single Ventricle Is Associated With Adverse Outcomes After Fontan Completion.

OBJECTIVES: To define the baseline characteristics of long-term tube-fed (TF) single ventricle patients, investigate associations between long-term enteral tube feeding and growth, and determine associations with long-term outcomes after Fontan procedure. STUDY DESIGN: We performed a retrospective cohort study of patients in the Australia and New Zealand Fontan Registry undergoing treatment at the Royal Children's Hospital, the Children's Hospital at Westmead, Royal Melbourne Hospital, and Royal Prince Alfred Hospital from 1981 to 2018. Patients were defined as TF or non-tube-fed (NTF) based on enteral tube feeding at the age of 90 days. Feeding groups were compared regarding body mass index (BMI) trajectory, BMI at last follow-up, and long-term incidence of severe Fontan failure. RESULTS: Of 390 patients (56 [14%] TF, 334 [86%] NTF), TF was associated with right ventricular dominance, hypoplastic left heart syndrome, Norwood procedure, increased procedures prior to Fontan, extracardiac conduit Fontan, Fontan fenestration, and atrioventricular valve repair/replacement. TF patients were less likely to be in the higher compared with lowest 0-6 month BMI trajectory (P < .01; P = .03), had lower 6 month weight-for-age z-scores (P < .01) and length-for-age z-scores (P = .01). TF were less likely to be overweight/obese at pediatric follow-up (hazard ratio [HR] = 0.31, 95% CI: 0.12-0.80; P = .02) and more likely to be underweight at adult follow-up (HR = 16.51; 5% CI: 2.70-101.10; P < .01). TF compared with NTF was associated with increased risk of severe Fontan failure (HR = 4.13; 95% CI = 1.65-10.31; P < .01). CONCLUSIONS: Prolonged infant enteral tube feeding is an independent marker of poor growth and adverse clinical outcomes extending long-term post-Fontan procedure.

Causes of hypercapnic respiratory failure and associated in-hospital mortality.

BACKGROUND AND OBJECTIVE: Hypercapnic respiratory failure (HRF) can occur due to severe respiratory disease but also because of multiple coexistent causes. There are few data on the prevalence of antecedent causes for HRF and the effect of these causes on prognosis, especially where study inclusion has not been biased with respect to primary diagnosis, interventions received or clinical outcome. We sought to determine the prevalence of pre-specified conditions among patients with HRF and to determine the effect of these causes on in-hospital mortality. METHODS: Cross-sectional study of patients with HRF from 2013 to 2017. Inclusion criteria were PaCO2  >45 mm Hg and pH ≤7.45. Causes of interest were identified using diagnosis codes from hospital records. We used directed acyclic graphs to inform logistic regression models for the outcome of in-hospital death. RESULTS: We identified 873 persons with HRF in the study period. Mean (SD) age was 69 years and 50.4% were males. Acidosis (pH <7.35) was present in 488 (55%) cases. Most (83%) had one or more of the following: obstructive lung disease, lower respiratory tract infection, congestive cardiac failure, sleep disordered breathing, neuromuscular disease, opioid or benzodiazepine use. In-hospital mortality was 12.8%. Obstructive lung disease and cardiac failure were associated with a lower risk of death, whereas respiratory tract infection and neuromuscular disease were associated with increased risk of death. CONCLUSION: HRF is associated with a range of potentially causative conditions, which significantly impact hospital survival. Systematic evaluation of patients with HRF may increase detection of treatable comorbidities.

Causes of hypercapnic respiratory failure: a population-based case-control study.

OBJECTIVE: There are no population-based data on the relative importance of specific causes of hypercapnic respiratory failure (HRF). We sought to quantify the associations between hospitalisation with HRF and potential antecedent causes including chronic obstructive pulmonary disease (COPD), obstructive sleep apnea, and congestive cardiac failure. We used data on the prevalence of these conditions to estimate the population attributable fraction for each cause. METHODS: A case-control study was conducted among residents aged ≥ 40 years from the Liverpool local government area in Sydney, Australia. Cases were identified from hospital records based on PaCO2 > 45 mmHg. Controls were randomly selected from the study population using a cluster sampling design. We collected self-reported data on medication use and performed spirometry, limited-channel sleep studies, venous sampling for N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, and sniff nasal inspiratory pressure (SNIP) measurements. Logistic regression analyses were performed using directed acyclic graphs to identify covariates. RESULTS: We recruited 42 cases and 105 controls. HRF was strongly associated with post-bronchodilator airflow obstruction, elevated NT-proBNP levels, reduced SNIP measurements and self-reported opioid medication use. There were no differences in the apnoea-hypopnea index or oxygen desaturation index between groups. COPD had the highest population attributable fraction (42%, 95% confidence interval 18% to 59%). CONCLUSIONS: COPD, congestive cardiac failure, and self-reported use of opioid medications, but not obstructive sleep apnea, are important causes of HRF among adults over 40 years old. No single cause accounts for the majority of cases based on the population attributable fraction.

Tree pollen exposure is associated with reduced lung function in children.

BACKGROUND: Allergic disease is a recognized global epidemic and a significant cause of ill health and poor quality of life. The prevalence of pollen allergy is high throughout the world, and pollen exposure itself plays a role in emergency department presentations and hospitalizations for asthma. Lung function and airway inflammation are important measures of asthma activity and control. OBJECTIVE: To examine associations between exposure to multiple pollen types and lung function and markers of airway inflammation at 8 and 14 years of age, and to explore potential modification by residential greenness. METHODS: A cohort of high-risk children living in Sydney, Australia had spirometry and fractional exhaled nitric oxide (FeNO) measured at 8 and 14 years of age. Ambient pollen concentration on the day of lung function measurement and up to three days prior was used as the exposure measure. Residential greenness was derived from satellite imagery. We modelled the association between six pollen types and lung function and FeNO. We also assessed modifying effects of residential greenness. RESULTS: Casuarina, cypress and Pinus pollen in the air the day before measurement and 3 days prior respectively, were associated with reduced lung function in 8-year-olds. The pollen exposures were associated with decreases in FEV1 and FVC; however, the FEV1 /FVC ratio was not affected. Effect modification by greenness was not observed due to loss of power. CONCLUSIONS & CLINICAL RELEVANCE: Airborne tree pollen of cypress, Casuarina and Pinus and not grass in some regions may be detrimental to childhood lung function.

Weight Gain Trajectories from Birth to Adolescence and Cardiometabolic Status in Adolescence.

OBJECTIVE: To assess the influence of the trajectory of weight gain from birth to adolescence on cardiovascular and metabolic risk. We studied childhood body mass index (BMI) trajectories from birth to age 14 years and cardiometabolic risk factors at age 14 years. STUDY DESIGN: In total, 410 children with weight and height measurements were assessed from birth throughout childhood, from the Childhood Asthma Prevention Study, a prospective community-based cohort. BMI trajectory groups were determined by latent basis growth mixture models. Of these subjects, 190 had detailed cardiometabolic risk factors assessed at age 14 years. RESULTS: Three BMI trajectory groups were identified; normal BMI, "early rising" excess BMI from 2 years, and "late rising" excess BMI from 5 years. Differences were found between normal and excess BMI in children at 14 years of age. In addition, children with an early rising BMI trajectory had statistically significantly higher central adiposity and a more atherogenic lipoprotein profile at age 14 years than children with a late rising BMI trajectory (P < .05). No differences between BMI trajectory groups in vascular structure or function was identified at age 14 years. CONCLUSIONS: Earlier onset of an elevated BMI trajectory persisting from birth to age 14 years results in an unfavorable cardiometabolic risk profile at age 14 years, including central adiposity and more atherogenic lipoproteins, independent of achieved BMI.

Comparison of model estimates from an intra-city land use regression model with a national satellite-LUR and a regional Bayesian Maximum Entropy model, in estimating NO2 for a birth cohort in Sydney, Australia.

BACKGROUND: Methods for estimating air pollutant exposures for epidemiological studies are becoming more complex in an effort to minimise exposure error and its associated bias. While land use regression (LUR) modelling is now an established method, there has been little comparison between LUR and other recent, more complex estimation methods. Our aim was to develop a LUR model to estimate intra-city exposures to nitrogen dioxide (NO2) for a Sydney cohort, and to compare those with estimates from a national satellite-based LUR model (Sat-LUR) and a regional Bayesian Maximum Entropy (BME) model. METHODS: Satellite-based LUR and BME estimates were obtained using existing models. We used methods consistent with the European Study of Cohorts for Air Pollution Effects (ESCAPE) methodology to develop LUR models for NO2 and NOx. We deployed 46 Ogawa passive samplers across western Sydney during 2013/2014 and acquired data on land use, population density, and traffic volumes for the study area. Annual average NO2 concentrations for 2013 were estimated for 947 addresses in the study area using the three models: standard LUR, Sat-LUR and a BME model. Agreement between the estimates from the three models was assessed using interclass correlation coefficient (ICC), Bland-Altman methods and correlation analysis (CC). RESULTS: The NO2 LUR model predicted 84% of spatial variability in annual mean NO2 (RMSE: 1.2 ppb; cross-validated R2: 0.82) with predictors of major roads, population and dwelling density, heavy traffic and commercial land use. A separate model was developed that captured 92% of variability in NOx (RMSE 2.3 ppb; cross-validated R2: 0.90). The annual average NO2 concentrations were 7.31 ppb (SD: 1.91), 7.01 ppb (SD: 1.92) and 7.90 ppb (SD: 1.85), for the LUR, Sat-LUR and BME models respectively. Comparing the standard LUR with Sat-LUR NO2 cohort estimates, the mean estimates from the LUR were 4% higher than the Sat-LUR estimates, and the ICC was 0.73. The Pearson's correlation coefficients (CC) for the LUR vs Sat-LUR values were r = 0.73 (log-transformed data) and r = 0.69 (untransformed data). Comparison of the NO2 cohort estimates from the LUR model with the BME blended model indicated that the LUR mean estimates were 8% lower than the BME estimates. The ICC for the LUR vs BME estimates was 0.73. The CC for the logged LUR vs BME estimates was r = 0.73 and for the unlogged estimates was r = 0.69. CONCLUSIONS: Our LUR models explained a high degree of spatial variability in annual mean NO2 and NOx in western Sydney. The results indicate very good agreement between the intra-city LUR, national-scale sat-LUR, and regional BME models for estimating NO2 for a cohort of children residing in Sydney, despite the different data inputs and differences in spatial scales of the models, providing confidence in their use in epidemiological studies.

Asthma and atopy prevalence are not reduced among former tuberculosis patients compared with controls in Lima, Peru.

BACKGROUND: Although there are theoretical reasons for believing that asthma and atopy may be negatively correlated with tuberculosis, epidemiological studies have had conflicting findings. OBJECTIVE: To determine if people with confirmed tuberculosis were less likely to be atopic and less likely to have atopic disease including asthma compared to those with no previous tuberculosis. METHODS: Patients in Lima, Peru with a prior history of tuberculosis were identified from clinic records in this cohort study. A representative sample of individuals without a prior tuberculosis diagnosis was recruited from the same community. Allergen skin prick testing was performed to classify atopic status. Allergic rhinitis was identified by history. Asthma was defined by symptoms and spirometry. Eosinophilic airway inflammation was measured using exhaled nitric oxide levels. RESULTS: We evaluated 177 patients with, and 161 individuals without, previous tuberculosis. There was a lower prevalence of atopy among people with prior tuberculosis on univariate analysis (odds ratio 0.57; 95% confidence interval 0.37-0.88) but, after adjustment for potential confounders, this was no longer statistically significant (aOR 0.64, 95% CI 0.41-1.01). The prevalence of allergic rhinitis (aOR 0.76, 95% CI 0.47 to 1.24 and asthma (aOR 1.18, 95% CI 0.69 to 2.00) did not differ significantly between the two groups. We also found no significant difference in the prevalence of elevated exhaled nitric oxide (aOR 1.30, 95% CI 0.78 to 2.17) or a combined index of atopic disease (aOR 0.86, 95% CI 0.54 to 1.36). CONCLUSION: In this urban environment in a middle-income country, prior tuberculosis may be associated with a reduced risk of atopy but does not protect against asthma and atopic disease.

Effect of season of birth on cord blood IgE and IgE at birth: A systematic review and meta-analysis.

BACKGROUND: Elevated cord blood IgE is important on the pathway to allergic disease. The association between season of birth and infant cord blood IgE is not well-established. Study findings differ on which birth season is associated with higher cord blood IgE risk and its magnitude. We conducted a systematic review and meta-analysis of studies on season of birth and cord blood IgE. METHODS: We searched Medline, Web of Science, Scopus and ProQuest Health databases, and reviewed reference lists of articles that met the inclusion criteria. All included studies measured IgE as a binary variable using various cut-off values. We performed multivariate-random-effects meta-analysis to handle an exposure with multiple categories of Season of Birth. RESULTS: Our search identified 275 records and 10 had sufficient data to be included in a meta-analysis. Relative to summer, winter birth had the greatest odds of high IgE (≥ 0.1IU/ml), meta-analysis OR = 1.24 (95%CI: 1.01-1.52). A similar OR, was found for IgE ≥ 0.5 IU/ml, OR = 1.30 (95%CI: 0.99-1.71). CONCLUSIONS: A winter season of birth was associated with statistically significant higher odds of elevated cord blood IgE at cut-off ≥ 0.1IU/ml but borderline at cut-off ≥ 0.5IU/ml. This winter effect is likely to be a marker for a range of other environmental exposures during specific stages of pregnancy, such as aeroallergen exposures, maternal infections and vitamin D levels. Further research is required to support our finding and to identify the exact mechanisms that lead to the winter season of birth effect on circulating IgE levels, as this may have implications for allergic disease prevention.

Impact of childhood asthma on growth trajectories in early adolescence: Findings from the Childhood Asthma Prevention Study (CAPS).

BACKGROUND AND OBJECTIVE: Understanding the associations between childhood asthma and growth in early adolescence by accounting for the heterogeneity of growth during puberty has been largely unexplored. The objective was to identify sex-specific classes of growth trajectories during early adolescence, using a method which takes the heterogeneity of growth into account and to evaluate the association between childhood asthma and different classes of growth trajectories in adolescence. METHODS: Our longitudinal study included participants with a family history of asthma born during 1997-1999 in Sydney, Australia. Hence, all participants were at high risk for asthma. Asthma status was ascertained at 8 years of age using data from questionnaires and lung function tests. Growth trajectories between 11 and 14 years of age were classified using a latent basis growth mixture model. Multinomial regression analyses were used to evaluate the association between asthma and the categorized classes of growth trajectories. RESULTS: In total, 316 participants (51.6% boys), representing 51.3% of the entire cohort, were included. Sex-specific classes of growth trajectories were defined. Among boys, asthma was not associated with the classes of growth trajectories. Girls with asthma were more likely than girls without asthma to belong to a class with later growth (OR: 3.79, 95% CI: 1.33, 10.84). Excluding participants using inhaled corticosteroids or adjusting for confounders did not significantly change the results for either sex. CONCLUSION: We identified sex-specific heterogeneous classes of growth using growth mixture modelling. Associations between childhood asthma and different classes of growth trajectories were found for girls only.

Supine awake oximetry as a screening tool for daytime hypercapnia in super-obese patients.

BACKGROUND: Evidence-based screening tools are required for detection of daytime hypercapnia in high-risk patient populations. AIMS: To determine the validity of supine awake oximetry as a test for daytime hypercapnia and severe sleep disordered breathing (SDB) in super-obese patients. METHODS: This was a cross-sectional diagnostic test evaluation of super-obese adults (body mass index >50 kg/m2 ) presenting to Liverpool Hospital, Australia, between 2009 and 2015 for diagnostic polysomnography (PSG) and arterial blood gas measurement. Supine awake oxygen saturation (SpO2 ) was determined using oximetry measurements from the first three awake epochs of raw PSG data. Sensitivity and specificity of SpO2 for detecting patients with daytime hypercapnia (PaCO2 >45 mmHg) and severe SDB (respiratory disturbance index (RDI) >30 events/h) were assessed at various cut-off points and displayed using a receiver operating characteristic (ROC) curve. Area under the ROC curve and positive and negative predictive values (PPV and NPV) in the present patient population were derived. RESULTS: Of 52 patients, 23 (44%) had daytime hypercapnia. SpO2 measured awake in the supine position was associated with the presence of daytime hypercapnia but not with the presence of severe SDB. Overall, awake supine SpO2 <91.2% had 34.8% sensitivity, 96.6% specificity and 88.8% PPV, and SpO2 <96.7% had 87.0% sensitivity, 20.7% specificity and 66.7% NPV for the presence of daytime hypercapnia. CONCLUSION: Awake supine oximetry is an easily performed test that may have novel use in identifying patients at high risk of respiratory failure. Future studies are required to evaluate prospectively its role in screening patients at risk of daytime hypercapnia.

Change in the manifestations of asthma and asthma-related traits in childhood: a latent transition analysis.

It is known that asthma is a heterogeneous entity whose manifestations vary with age. Our objective was to examine changes in the manifestation of asthma and asthma-related traits in childhood by defining empirically derived childhood asthma phenotypes and examining their transitions over time.To define the phenotypes we used data on respiratory symptoms, healthcare utilisation, medications, spirometry, airway hyperresponsiveness (AHR), exhaled nitric oxide concentration and atopy from a birth cohort recruited on the basis of having a first-degree relative with asthma. Data were acquired at ages 1.5-11.5 years and analysed using latent transition analysis.In a study population of 370 participants, we classified subjects into four phenotypes: 1) nonatopic, few symptoms (prevalence range from 1.5 to 5 years: 52-60%), 2) atopic, few symptoms (3-21%), 3) nonatopic, asthma and rhinitis symptoms (13-35%), and 4) atopic, asthma and rhinitis symptoms (2-14%) in early childhood; and 1) nonatopic, no respiratory disease (prevalence range from 8 to 11.5 years: 41-46%), 2) atopic, no respiratory disease (23-33%), 3) nonatopic, asthma symptoms, no AHR or airway inflammation (8-12%) and 4) atopic asthma (19%) in mid-childhood. Transitioning between phenotypes was common in early childhood, but less common in later childhood.This analysis represents the first attempt to incorporate longitudinal patterns of several manifestations of asthma into a single model to simultaneously define phenotypes and examine their transitions over time. It provides quantitative support for the view that asthma is a heterogeneous entity, and that some children with wheeze and other respiratory symptoms in early life progress to asthma in mid-childhood, while others become asymptomatic.

Absence of back to school peaks in human rhinovirus detections and respiratory symptoms in a cohort of children with asthma.

Much of what is known about the seasonality of human rhinovirus (hRV) infections has been learned from the study of acute asthma exacerbations presenting to emergency care, including those among children at the start of the school term. Much less is known about the patterns of hRVs in the community. In this study, viruses and day-to-day symptoms of asthma and colds were monitored twice weekly in 67 children with asthma aged 5-12 years, over a 15 month period in Sydney, Australia. Overall hRV was detected in 314/1232 (25.5%) of nasal wash samples and 142/1231 (11.5%) of exhaled breath samples; of these, 231 and 24 respectively were genotyped. HRVs were detected with similar prevalence rate throughout the year, including no peak in hRV prevalence following return to school. No peaks were seen in asthma and cold symptoms using twice-weekly diary records. However, over the same period in the community, there were peaks in asthma emergency visits both at a large local hospital and in state-wide hospitalizations, following both return to school (February) and in late autumn (May) in children of the same age. This study suggests that hRV infections are common throughout the year among children, and differences in virus prevalence alone may not account for peaks in asthma symptoms.

Cervicitis aetiology and case definition: a study in Australian women attending sexually transmitted infection clinics.

OBJECTIVES: Studies examining cervicitis aetiology and prevalence lack comparability due to varying criteria for cervicitis. We aimed to outline cervicitis associations and suggest a best case definition. METHODS: A cross-sectional study of 558 women at three sexually transmitted infection clinics in Sydney, Australia, 2006-2010, examined pathogen and behavioural associations of cervicitis using three cervicitis definitions: 'microscopy' (>30 pmnl/hpf (polymorphonuclear leucocytes per high-powered field on cervical Gram stain)), 'cervical discharge' (yellow and/or mucopurulent cervical discharge) or 'micro+cervical discharge' (combined 'microscopy' and 'cervical discharge'). RESULTS: Chlamydia trachomatis (CT), Mycoplasma genitalium (MG), Trichomonas vaginalis (TV) and Neisseria gonorrhoeae (NG) had the strongest associations with cervicitis definitions 'micro+cervical discharge': CT adjusted prevalence ratio (APR)=2.13 (95% CI 1.38 to 3.30) p=0.0006, MG APR=2.21 (1.33 to 3.69) p=0.002, TV APR=2.37 (1.44 to 3.90) p=0.0007 NG PR=4.42 (3.79 to 5.15) p<0.0001 and 'cervical discharge': CT APR=1.90 (1.25 to 2.89) p=0.003, MG APR=1.93 (1.17 to 3.19) p=0.011, TV APR=2.02 (1.24 to 3.31) p=0.005 NG PR=3.88 (3.36 to 4.48) p<0.0001. Condom use for vaginal sex 'always/sometimes' reduced cervicitis risk: ('micro+cervical discharge') APR=0.69 (0.51 to 0.93) p=0.016. Combined population attributable risk % (PAR%) of these four pathogens was only 18.0% with a protective PAR% of condoms of 25.7%. Exposures not associated with cervicitis included bacterial vaginosis, Mycoplasma hominis, Ureaplasma urealyticum, herpes simplex virus 1&2, cytomegalovirus, Candida, age, smoking and hormonal contraception. CONCLUSIONS: Cervicitis was associated with CT, MG, TV and NG with combined PAR% of these pathogens only 18% in this setting, suggesting other factors are involved. Condoms significantly reduced cervicitis risk. Cervicitis definitions with best clinical utility and pathogen prediction were 'cervical discharge' and 'micro+cervical discharge'.

Rhinoviruses significantly affect day-to-day respiratory symptoms of children with asthma.

BACKGROUND: Viruses are frequently associated with acute exacerbations of asthma, but the extent to which they contribute to the level of day-to-day symptom control is less clear. OBJECTIVE: We sought to explore the relationship between viral infections, host and environmental factors, and respiratory symptoms in children. METHODS: Sixty-seven asthmatic children collected samples twice weekly for an average of 10 weeks. These included nasal wash fluid and exhaled breath for PCR-based detection of viral RNA, lung function measurements, and records of medication use and asthma and respiratory symptoms in the previous 3 days. Atopy, mite allergen exposure, and vitamin D levels were also measured. Mixed-model regression analyses were performed. RESULTS: Human rhinoviruses (hRVs) were detected in 25.5% of 1232 nasal samples and 11.5% of breath samples. Non-hRV viruses were detected in less than 3% of samples. hRV in nasal samples was associated with asthma symptoms (cough and phlegm: odds ratio = 2.0; 95% CI = 1.4-2.86, P = .0001; wheeze and chest tightness: odds ratio = 2.34, 95% CI = 1.55-3.52, P < .0001) and with cold symptoms, as reported concurrently with sampling and 3 to 4 days later. No differences were found between the 3 hRV genotypes (hRV-A, hRV-B, and hRV-C) in symptom risk. A history of inhaled corticosteroid use, but not atopic status, mite allergen exposure, or vitamin D levels, modified the association between viruses and asthma symptoms. CONCLUSION: The detection of nasal hRV was associated with a significantly increased risk of day-to-day asthma symptoms in children. Host, virus genotype, and environmental factors each had only a small or no effect on the relationship of viral infections to asthma symptoms.

Are measures and related symptoms of cachexia recorded as outcomes in gastrointestinal cancer chemotherapy clinical trials?

BACKGROUND: Cachexia is prevalent in gastrointestinal cancers and worsens patient outcomes and chemotherapy compliance. We examined to what extent registered gastrointestinal cancer chemotherapy clinical trials record measures and related symptoms of cachexia as outcomes, and whether these were associated with trial characteristics. METHODS: Four public trial registries (2012-2022) were accessed for Phase II and/or III randomized controlled pancreatic, gastric, and colorectal cancer chemotherapy trial protocols. Trial outcome measures of overall survival and toxicity/side effects, and those related to cachexia [physical activity, weight/body mass index (BMI), dietary limitations, caloric intake, lean muscle mass] and symptoms (appetite loss, diarrhoea, pain, fatigue/insomnia, constipation, nausea, vomiting, and oral mucositis) were extracted, along with the number and types of performance status and patient-reported outcomes (PROs) tools. Data were summarized descriptively. Chi-square tests examined associations between outcomes and trial characteristics (cancer type, trial location, funding source, PROs tools, and commencement year). Statistical significance was set at P < 0.05. RESULTS: We included 540 trial protocols (pancreatic (35.2%), colorectal (33.3%) and gastric (31.5%)), with most trials from Europe (44.1%). Trial lead investigator was from academia (28.3%), industry (27.6%) and government (26.3%). Allied health professional involvement (26.9%) occurred at eligibility. Adjuvant therapy in trials was mainly treatment-related (68.1%). Additional medication included anti-nausea (2.2%) and analgesia (0.9%). Trial protocols mostly recorded overall survival (90.4%) and toxicity (78.9%), and the symptoms appetite loss (26.1%) and diarrhoea (19.1%), with the other symptoms recorded in <10% of the trials. Reporting of physical activity (P = 0.001), dietary limitations (P = 0.002), lean muscle mass (P = 0.027), appetite loss (P < 0.001), pain (P = 0.001), nausea (P = 0.012), and oral mucositis (P = 0.049) varied depending cancer type. Toxicity/side effects (P = 0.022), physical activity (P < 0.001), appetite loss, nausea, and vomiting (all P < 0.001), diarrhoea (P = 0.010), pain (P = 0.001), fatigue/insomnia (P = 0.001) varied depending on the trial location. Trial funding was predominantly from private/industry (34.3%) and influenced the reporting of overall survival (P = 0.049), weight/BMI (P = 0.005), caloric intake (P = 0.015), and pain (P = 0.031). Performance status and PROs tools were mentioned in 91.2% and 46.3% of the trials, respectively. Trials that incorporated PROs tools were more likely to report cachexia related outcomes, except for overall survival, lean muscle mass, and oral mucositis. The proportion of trials measuring weight/BMI increased with trial commencement year (P = 0.04). CONCLUSIONS: Cachexia-related outcomes were under-recorded in gastrointestinal cancer chemotherapy trials. As trial patients experience a high symptom burden, cachexia-relevant measures and symptoms should be assessed throughout the trial, and integrated with primary endpoints to support their progress.

Impact of growth, gonadal hormones, adiposity and the sodium-to-potassium ratio on longitudinal adolescent measures of blood pressure at puberty.

Blood pressure (BP) rises rapidly at puberty. While this is partly due to normal development, factors like excess adiposity and a high intake of dietary sodium relative to potassium may contribute to a true increase in hypertension risk. This study aimed to assess the relative impact of growth, gonadal hormones, adiposity and the sodium-to-potassium ratio (Na:K) on longitudinal BP measures at puberty. This study analysed data from a three-year longitudinal cohort study of pubertal adolescents. Anthropometry, body composition (bio-electrical impedance), serum testosterone and oestradiol (mass spectrometry) were measured annually. Na:K was measured from three-monthly urine samples. These variables were used to predict annual BP measures using mixed modelling and ordinal regression. Data from 325 adolescents (11.7 ± 1.0 y; 55% male) were analysed, showing typical growth patterns at puberty. Systolic BP increased over time in both sexes (p < 0.01), with boys exhibiting a significantly steeper rise compared to girls. Adiposity variables (BMI z-score, percent body fat, fat mass, waist-to-height ratio) strongly and consistently predicted systolic and diastolic BP in both sexes (all p < 0.05). Systolic BP was also significantly and positively related to height (p < 0.05). No associations with BP were identified in either sex for gonadal hormones or Na:K. Similar results were obtained when BP was classified into hypertension categories. Relative to other developmental and diet-related variables tested, adiposity was found to be the strongest most consistent predictor of BP in pubertal adolescents. Findings highlight the importance of dedicated youth obesity management interventions and policy measures for reducing long-term hypertension and cardiovascular disease risks.Australian New Zealand Clinical Trials Registry ACTRN12617000964314.

Association of urinary sex hormones with mood and behavior changes in a community adolescent cohort.

OBJECTIVE: To examine the contribution of variation in sex hormone excretion to mood and behavioral changes in adolescent females and males. DESIGN: Prospective, longitudinal observational cohort study. METHODS: Participants were 342 volunteers aged 10-12 years living in rural Australia. Urinary estradiol and testosterone levels measured by liquid chromatography-mass spectrometry were obtained at three-month intervals for three years. Integrated measures (area-under-curve) of urinary steroid excretion summarised as absolute and variability during each 12-month period of the study. Psychosocial data were gathered annually with the primary outcome of depressive symptomatology. Secondary outcomes were the other subscales of the Youth Self-Report, impulsive-aggression, sleep habits, and self-harm. RESULTS: 277 (158 male) participants contributed data over the full duration of the study and could be included in the analyses. In females, analyses of absolute urine hormone levels found no relationship between estradiol and any outcome, but higher testosterone was significantly associated with depression and poorer sleep. Greater variability of both urine estradiol and testosterone was associated with lower total psychopathology, anxious/depressed and social problems scores. Greater variability in urine estradiol was associated with lower attention problems and impulsive aggression in females. In males, higher testosterone and estradiol levels were associated with rule-breaking, and poorer sleep, and no associations were found for gonadal hormone variability for males. CONCLUSIONS: Longitudinal measurement of both iso-sexual and contra-sexual gonadal hormones contributes to a more nuanced view of the impact of sex steroids on mood and behavior in adolescents. These findings may enlighten the understanding of the impact of sex steroids during normal male and female puberty with implications for hormone replacement therapies as well as management of common mood and behavioral problems.