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.

Estimating the contribution of subclinical tuberculosis disease to transmission: An individual patient data analysis from prevalence surveys.

Background: Individuals with bacteriologically confirmed pulmonary tuberculosis (TB) disease who do not report symptoms (subclinical TB) represent around half of all prevalent cases of TB, yet their contribution to Mycobacterium tuberculosis (Mtb) transmission is unknown, especially compared to individuals who report symptoms at the time of diagnosis (clinical TB). Relative infectiousness can be approximated by cumulative infections in household contacts, but such data are rare. Methods: We reviewed the literature to identify studies where surveys of Mtb infection were linked to population surveys of TB disease. We collated individual-level data on representative populations for analysis and used literature on the relative durations of subclinical and clinical TB to estimate relative infectiousness through a cumulative hazard model, accounting for sputum-smear status. Relative prevalence of subclinical and clinical disease in high-burden settings was used to estimate the contribution of subclinical TB to global Mtb transmission. Results: We collated data on 414 index cases and 789 household contacts from three prevalence surveys (Bangladesh, the Philippines, and Viet Nam) and one case-finding trial in Viet Nam. The odds ratio for infection in a household with a clinical versus subclinical index case (irrespective of sputum smear status) was 1.2 (0.6-2.3, 95% confidence interval). Adjusting for duration of disease, we found a per-unit-time infectiousness of subclinical TB relative to clinical TB of 1.93 (0.62-6.18, 95% prediction interval [PrI]). Fourteen countries across Asia and Africa provided data on relative prevalence of subclinical and clinical TB, suggesting an estimated 68% (27-92%, 95% PrI) of global transmission is from subclinical TB. Conclusions: Our results suggest that subclinical TB contributes substantially to transmission and needs to be diagnosed and treated for effective progress towards TB elimination. Funding: JCE, KCH, ASR, NS, and RH have received funding from the European Research Council (ERC) under the Horizon 2020 research and innovation programme (ERC Starting Grant No. 757699) KCH is also supported by UK FCDO (Leaving no-one behind: transforming gendered pathways to health for TB). This research has been partially funded by UK aid from the UK government (to KCH); however, the views expressed do not necessarily reflect the UK government's official policies. PJD was supported by a fellowship from the UK Medical Research Council (MR/P022081/1); this UK-funded award is part of the EDCTP2 programme supported by the European Union. RGW is funded by the Wellcome Trust (218261/Z/19/Z), NIH (1R01AI147321-01), EDTCP (RIA208D-2505B), UK MRC (CCF17-7779 via SET Bloomsbury), ESRC (ES/P008011/1), BMGF (OPP1084276, OPP1135288 and INV-001754), and the WHO (2020/985800-0).

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.

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.

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.

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.

Prevalence and genetic basis of first-line drug resistance of Mycobacterium tuberculosis in Ca Mau, Vietnam.

Background and objective: Data on the prevalence of anti-tuberculous drug resistance and its association with genetic mutations in Mycobacterium tuberculosis are limited. Our study explores the genomics of tuberculosis in Ca Mau, Vietnam. Methods: Patients ≥15 years in Ca Mau Province, Vietnam, were screened annually for tuberculosis between 2014 and 2017. Isolates underwent drug susceptibility testing (DST) using the breakpoint method. DNA was extracted and whole genome sequencing (WGS) was performed. Results: We identified 365 positive sputum cultures for M. tuberculosis and processed 237 for DST and 265 for WGS. Resistance to isoniazid was present in 19.8% (95% CI 14.7 to 24.9%), rifampicin in 3.5% (1.1 to 5.7%) and ethambutol in 2.5% (0.9 to 5.4%) of isolates. Relevant mutations in rpoB gene were detected in 3.8% (1.8 to 6.8%). katG, inhA or fabG1 mutations were found in 19.6% (15.0 to 24.9%) with KatG being most common at 12.8% (9.1-17.5%). We found 38.4% of isolates were of Beijing lineage, 49.4% East-African-Indian lineage and 8.4% European-American lineage. There were no associations between resistance profiles and clinical features. Conclusion: The high burden of isoniazid resistance and the katG mutation highlights the challenges facing Vietnam in its efforts to achieve its EndTB goals.

Body Mass Index Trajectory and Outcome Post Fontan Procedure.

Background Patients with a single ventricle who experience early life growth failure suffer high morbidity and mortality in the perisurgical period. However, long-term implications of poor infant growth, as well as associations between body mass index (BMI) and outcome in adulthood, remain unclear. We aimed to model BMI trajectories of patients with a single ventricle undergoing a Fontan procedure to determine trajectory-based differences in baseline characteristics and long-term clinical outcomes. Methods and Results We performed a retrospective analysis of medical records from patients in the Australia and New Zealand Fontan Registry receiving 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. BMI trajectories were modeled in 496 patients using latent class growth analysis from 0 to 6 months, 6 to 60 months, and 5 to 16 years. Trajectories were compared regarding long-term incidence of severe Fontan failure (defined as mortality, heart transplantation, Fontan takedown, or New York Heart Association class III/IV heart failure). Three trajectories were found for male and female subjects at each age group-lower, middle, higher. Subjects in the lower trajectory at 0 to 6 months were more likely to have an atriopulmonary Fontan and experienced increased mortality long term. No association was found between higher BMI trajectory, current BMI, and long-term outcome. Conclusions Poor growth in early life correlates with increased long-term severe Fontan failure. Delineation of distinct BMI trajectories can be used in larger and older cohorts to find optimal BMI targets for patient outcome.

Feasibility and preliminary efficacy of iConquerFear: a self-guided digital intervention for fear of cancer recurrence.

PURPOSE: Approximately 50% of cancer survivors experience moderate-severe fear of cancer recurrence (FCR). Self-guided digital interventions have potential to address the high level of FCR-related unmet needs at scale, but existing digital interventions have demonstrated variable engagement and efficacy. This study aimed to evaluate the feasibility and preliminary efficacy of iConquerFear, a five-module self-guided digital FCR intervention. METHODS: Eligible curatively treated breast cancer survivors were recruited. Participants reporting clinically significant FCR (≥ 13 on the Fear of Cancer Recurrence Inventory-Short Form; FCRI-SF) were given access to iConquerFear. Feasibility was indicated by > 50% of eligible participants enrolling in iConquerFear and recording moderate (≥ 120 min) or greater usage. Preliminary efficacy was evaluated via changes in self-reported FCR severity, anxiety, depression, intrusions and metacognitions from baseline to immediately and 3 months post-intervention. RESULTS: Fifty-four (83%) of 65 eligible participants enrolled in iConquerFear; six subsequently withdrew. Thirty-nine (83%) participants recorded moderate (n = 24; 120-599 min) or high (n = 15; ≥ 600 min) usage. Engagement levels increased with participant age (p = 0.043), but were lower in participants with higher baseline FCR (p = 0.028). Qualitative feedback indicated engagement was sometimes limited by difficulties with navigation and relating to featured survivors. Participants reported significantly improved FCR (mean reduction (95%CI): baseline to post-intervention - 3.44 (- 5.18, - 1.71), baseline to 3-month follow-up - 4.52 (- 6.25, - 2.78), p = < 0.001). CONCLUSION: iConquerFear is a feasible and potentially efficacious intervention for reducing FCR in breast cancer survivors. Easier navigation and more relatable examples may enhance engagement. IMPLICATIONS FOR CANCER SURVIVORS: iConquerFear may help address moderate but burdensome FCR levels in cancer survivors.

Associations Between Ambient Particulate Air Pollution and Cognitive Function in Indonesian Children Living in Forest Fire-Prone Provinces.

Smoke from forest fires can reach hazardous levels for extended periods of time. We aimed to determine if there is an association between particulate matter ≤2.5 µm in aerodynamic diameter (PM2.5) and living in a forest fire-prone province and cognitive function. We used data from the Indonesian Family and Life Survey. Cognitive function was assessed by the Ravens Colored Progressive Matrices (RCPM). We used regression models to estimate associations between PM2.5 and living in a forest fire-prone province and cognitive function. In multivariable models, we found very small positive relationships between PM2.5 levels and RCPM scores (PM2.5 level at year of survey: ß = 0.1%; 95% confidence interval (CI) [0.01, 0.19%]). There were no differences in RCPM scores for children living in forest fire-prone provinces compared with children living in non-forest fire-prone provinces (mean difference = -1.16%, 95% CI [-2.53, 0.21]). RCPM scores were lower for children who had lived in a forest fire-prone province all their lives compared with children who lived in a non-forest fire-prone province all their life (ß = -1.50%; 95% CI [-2.94, -0.07]). Living in a forest fire-prone province for a prolonged period of time negatively affected cognitive scores after adjusting for individual factors.

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.

Ability of the LACE index to predict 30-day hospital readmissions in patients with community-acquired pneumonia.

BACKGROUND AND OBJECTIVE: Hospital readmissions within 30 days are used as an indicator of quality of hospital care. We aimed to evaluate the ability of the LACE (Length of stay, Acuity of admission, Comorbidities based on Charlson comorbidity score and number of Emergency visits in the last 6 months) index to predict the risk of 30-day readmissions in patients hospitalised for community-acquired pneumonia (CAP). METHODS: In this retrospective cohort study a LACE index score was calculated for patients with a principal diagnosis of CAP admitted to a tertiary hospital in Sydney, Australia. The predictive ability of the LACE score for 30-day readmissions was assessed using receiver operator characteristic curves with C-statistic. RESULTS: Of 3996 patients admitted to hospital for CAP at least once, 8.0% (n=327) died in hospital and 14.6% (n=584) were readmitted within 30 days. 17.8% (113 of 636) of all 30-day readmissions were again due to CAP, followed by readmissions for chronic obstructive pulmonary disease, heart failure and chest pain. The LACE index had moderate discriminative ability to predict 30-day readmission (C-statistic=0.6395) but performed poorly for the prediction of 30-day readmissions due to CAP (C-statistic=0.5760). CONCLUSIONS: The ability of the LACE index to predict all-cause 30-day hospital readmissions is comparable to more complex pneumonia-specific indices with moderate discrimination. For the prediction of 30-day readmissions due to CAP, the performance of the LACE index and modified risk prediction models using readily available variables (sex, age, specific comorbidities, after-hours, weekend, winter or summer admission) is insufficient.

Bumpy and Smoother Pathways of Puberty Hormone Change: A Novel Way to Define Gonadal Hormone Trajectories in Adolescents.

CONTEXT: The study of gonadal hormone effects on adolescent wellbeing has been limited by logistical challenges. Urine hormone profiling offers new opportunities to understand the health and behavioral implications of puberty hormones. OBJECTIVE: To characterize pubertal change in urinary testosterone and estradiol among male and female adolescents, respectively. DESIGN: Three-year prospective cohort study. SETTING: Australian regional community. PARTICIPANTS: 282 (163 male) normally developing adolescents aged 11.8 ± 1.0 years at baseline. MAIN OUTCOME MEASURE: Quarterly urine measurements of testosterone and estradiol (mass spectrometry); annual anthropometric assessment and Tanner stage (TS) self-report. RESULTS: Two-class sigmoidal and quadratic growth mixture models (centered on age at TS3) were identified as best-fit for describing testosterone (male) and estradiol (female) change. Classes 1 (male: 63%; female: 82%) and 2 (male: 37%; female: 18%) were respectively named the "stable" and "unstable" trajectories, characterized by different standard deviation of quarterly hormone change and magnitude of hormone peaks and troughs (all P < 0.001). Compared with class 1 (stable), class 2 males were taller at baseline (154 vs 151 cm), reported earlier and faster TS progression (P < 0.01), and showed higher serum testosterone levels at baseline and 3 years (P ≤ 0.01). Class 2 females exhibited smaller height and weight gains over the 3 years and had higher baseline serum estradiol (249 vs 98 pmol/L; P = 0.002) than class 1. CONCLUSIONS: Adolescents showed 2 distinct urinary gonadal hormone trajectories, characterized by stability of change over time, which were not associated with consistent anthropometric differences. Results provide a methodology for studying gonadal hormone impacts on other aspects of biopsychosocial wellbeing. Identification of potential "at-risk" hormone groups would be important for planning supportive interventions.

Foot Length Growth as a Novel Marker of Early Puberty.

Foot growth is part of overall pubertal growth but its relation to other anthropometric and hormonal changes is unclear. Our objective was to determine how foot length changes relate to changes in other growth parameters (height and weight), Tanner stage, and serum hormones. Adolescents (n = 342) were recruited to a 3-year longitudinal cohort study, underwent annual anthropometric assessments (height, weight, and foot length), and provided self-rated Tanner staging. They also provided blood samples that were analyzed using liquid chromatography-tandem mass spectrometry for serum testosterone and estradiol and classified as pre-pubertal or pubertal based on circulating hormone levels. Average annual percent increase in foot length was greater for pre-pubertal adolescents compared with pubertal. Increased foot length was associated with increases in height, weight, Tanner stage, and serum hormones in males and pre-menarcheal females but not post-menarcheal females. Foot length offers a novel, noninvasive, cost-effective, and easily demonstrable marker of early pubertal changes.

Self-rated Tanner stage and subjective measures of puberty are associated with longitudinal gonadal hormone changes.

Introduction In large community-based studies of puberty, Tanner staging by a clinician is often not possible. We compared self-rated Tanner staging and other subjective ratings of pubertal development with serum hormone levels measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS) to reassess the utility of self-rated pubertal stage using highly sensitive and specific hormone analysis. Methods Adolescents and their parents enrolled in the Adolescent Rural Cohort study of Hormones and health, Education, environments and Relationships (ARCHER) answered annual survey questions on pubertal development. Annually, adolescents provided blood samples for serum testosterone and estradiol measured by LC-MS/MS. Results Longitudinally, self-rated Tanner stage was positively associated with serum testosterone and estradiol levels in both sexes. Confirmation by adolescent and parent that puberty had commenced was associated with higher gonadal hormone levels in both sexes. Parent and adolescent responses demonstrated 'fair' to 'moderate' agreement. Conclusions Over a 3-year follow-up, self-rated Tanner staging and simple questions regarding pubertal onset and development are positively associated with adolescent gonadal hormone concentrations in serum measured by mass spectrometry. Thus, self-report of puberty stage still has a role in large community-based studies where physical examination is not feasible.

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.