Thymidylate synthase expression and outcome of patients receiving pemetrexed for advanced nonsquamous non-small-cell lung cancer in a prospective blinded assessment phase II clinical trial

INTRODUCTION In retrospective analyses of patients with nonsquamous non-small-cell lung cancer treated with pemetrexed, low thymidylate synthase (TS) expression is associated with better clinical outcomes. This phase II study explored this association prospectively at the protein and mRNA-expression level. METHODS Treatment-naive patients with nonsquamous non-small-cell lung cancer (stage IIIB/IV) had four cycles of first-line chemotherapy with pemetrexed/cisplatin. Nonprogressing patients continued on pemetrexed maintenance until progression or maximum tolerability. TS expression (nucleus/cytoplasm/total) was assessed in diagnostic tissue samples by immunohistochemistry (IHC; H-scores), and quantitative reverse-transcriptase polymerase chain reaction. Cox regression was used to assess the association between H-scores and progression-free/overall survival (PFS/OS) distribution estimated by the Kaplan-Meier method. Maximal χ analysis identified optimal cutpoints between low TS- and high TS-expression groups, yielding maximal associations with PFS/OS. RESULTS The study enrolled 70 patients; of these 43 (61.4%) started maintenance treatment. In 60 patients with valid H-scores, median (m) PFS was 5.5 (95% confidence interval [CI], 3.9-6.9) months, mOS was 9.6 (95% CI, 7.3-15.7) months. Higher nuclear TS expression was significantly associated with shorter PFS and OS (primary analysis IHC, PFS: p < 0.0001; hazard ratio per 1-unit increase: 1.015; 95%CI, 1.008-1.021). At the optimal cutpoint of nuclear H-score (70), mPFS in the low TS- versus high TS-expression groups was 7.1 (5.7-8.3) versus 2.6 (1.3-4.1) months (p = 0.0015; hazard ratio = 0.28; 95%CI, 0.16-0.52; n = 40/20). Trends were similar for cytoplasm H-scores, quantitative reverse-transcriptase polymerase chain reaction and other clinical endpoints (OS, response, and disease control). CONCLUSIONS The primary endpoint was met; low TS expression was associated with longer PFS. Further randomized studies are needed to explore nuclear TS IHC expression as a potential biomarker of clinical outcomes for pemetrexed treatment in larger patient cohorts. © 2013 by the International Association for the Study of Lung Cancer.

Objectively measured physical activity behavior in children attending a half day preschool program

Obesity rates are increasing in children of all ages, and reduced physical activity (PA) is a likely contributor to this trend. Little is known about the physical activity behavior of preschool-age children, or about the influence of preschool attendance on physical activity. Purpose The purpose of this study was to quantify the physical activity levels of children attending a center-based half-day preschool program. Methods Forty-two 3-to-5-year old children (Mean age = 4.0 ± 0.7, 54.8% Male, Mean BMI = 16.5 ± 5.5, Mean BMI %tile = 52.1 ± 33.5) from four class groups (two morning and two afternoon), wore an Actigraph 7164 accelerometer for the entire halfday program (including classroom learning experiences, snack and recess time) 2 times per week, for 10 weeks (20 activity monitoring records in total). Activity counts for each 5-sec interval were uploaded to a customized data reduction program to determine total counts, minutes of moderate PA (MPA) (3–5.9 METs), and minutes of vigorous PA (VPA) (> = 6 METs) per session. Counts were categorized as either MPA or VPA using the cutpoints developed by Sirard and colleagues (2001). Results Across the four 2.5 hour programs, the average MPA, VPA and total counts (× 103) were 12.4 ± 3.1 minutes, 18.3 ± 4.6 minutes, and 171.1 ± 29.7 counts, respectively. Thus, on average, children accumulated just over 12 minutes of moderateto-vigorous PA per hour of program attendance. The PA variables did not differ significantly by gender, weight status, or time of day. There were, however, significant age differences, with 3-year-olds exhibiting significantly less PA than their 4- and 5-year-old counterparts. Conclusions These results suggest that young children are relatively lowactive while attending preschool. Accordingly, interventions to increase movement opportunities during the preschool day are warranted.

The provision of compulsory school physical activity : associations with physical activity, fitness and overweight in childhood and twenty years later

Background
To determine whether the provision of higher levels of compulsory school physical activity is associated with higher physical activity and fitness levels and less overweight in childhood and 20 years later.

Methods
As part of the 1985 Australian Schools Health and Fitness Survey, 109 schools reported how much compulsory physical education (PE) and school sport they provided and were classified as low (<110 and <150 minutes/week for primary and secondary schools, respectively), medium (110–149 and 150–189 minutes/week for primary and secondary schools, respectively) or high (≥150 and ≥190 minutes/week for primary and secondary schools, respectively) compulsory physical activity schools by tertile cutpoints. 6,412 children reported frequency and duration of school (PE and sport) and non-school (commuting and non-organised exercise) physical activity and had height and weight measured; overweight was defined using body mass index (BMI) (m/kg²) cutpoints. 9, 12 and 15 year-olds (n = 2,595) completed a cycle ergometer fitness test (physical working capacity at heart rate 170, PWC₁₇₀). At follow-up in 2004–5, 2,346 participants kept a pedometer record, completed the International Physical Activity Questionnaire and/or a PWC₁₇₀ fitness test; and had height and weight measured (overweight = BMI≥25 m/kg²).

Results
At baseline and follow-up, median total physical activity, fitness and BMI were similar in participants who attended low, medium and high physical activity schools, and those attending high physical activity schools reported only modestly higher school physical activity. There was no difference in the prevalence of high total physical activity and fitness levels in childhood or adulthood across compulsory school physical activity categories. The prevalence of overweight in childhood and adulthood was similar across low, medium and high compulsory physical activity schools.

Conclusion
The amount of compulsory physical activity reported by schools was not associated with total physical activity, fitness or overweight in childhood or in adulthood. Policies promoting amounts of compulsory school physical activity in this range may not be sufficient to increase physical activity and fitness or reduce the prevalence of obesity in children.

Predictors of body mass index change in Australian primary school children

Objective. To assess associations between multiple potential predictors and change in child body mass index (BMI). Methods.In the 1997 Health of Young Victorians Study, children in Grades preparatory to three (aged 510 years) had their height and weight measured. Parents provided information on potential predictors of childhood overweight across six domains (children’s diet, children’s activity level, family composition, sociodemographic factors, prenatal factors and parental adiposity). Measures were repeated three years later in 2000/1. BMI was transformed to standardised (z) scores using the US 2000 Growth Chart data and children were classified as non-overweight or overweight according to international cutpoints.Regression analyses, including baseline BMI z-score as a covariate, assessed the contribution of each potential predictor to change in BMI z-score, development of overweight and spontaneous resolution of overweight in 1 373 children.Results. BMI z-score change was positively associated with frequency of take-away food, food quantity, total weekly screen time, non-Australian paternal country of birth, maternal smoking during pregnancy, and maternal and paternal BMI.Inverse associations were noted for the presence of siblings and rural residence (all pB0.05). Predictors of categorical change (development and resolution of overweight) were less clearly identified, apart from an association between maternal BMI and overweight development (p0.02). Multivariable models suggested individual determinants have a cumulative effect on BMI change. Conclusions. Strong short-term tracking of BMI makes it difficult to identify predictors of change. Nonetheless, putative determinants across all domains assessed were independently associated with adiposity change. Multi-faceted solutions are likely to be required to successfully deal with the complexities of childhood overweight.

Screening children with developmental coordination disorder : the development of the caregiver assessment of movement participation

This study investigated the psychometric properties of the Caregiver Assessment of Movement Participation (CAMP), which was developed to measure and identify children with movement participation problems in home contexts. The test-retest reliability, as well as the concurrent and contrast-group validity of the 35-item parent-proxy CAMP, was examined on 312 children aged 5 to 8 years using intraclass correlation, factor analysis, and the Rasch model. Initial findings on the CAMP appeared to support its validity. Testing on other properties from a practical perspective, such as finding the best rating scale structure and cutpoints, are recommended before using the instrument for child health surveillance screening.

Differences in physical activity during school recess

BACKGROUND: School recess provides a daily opportunity for physical activity engagement. The purpose of this study was to examine physical activity levels during recess by gender, ethnicity, and grade, and establish the contribution of recess to daily school physical activity levels.
METHODS: Two hundred and ten children (45% boys) from grades 3 to 6 in 4 elementary schools had their physical activity during school quantified using uni-axial accelerometry every 5 seconds for 5 consecutive school days. Data were collected in fall 2009. The proportion of time spent engaged in physical activity during daily school recess was determined using existing age-appropriate cutpoints. The relative contribution of recess to school day physical activity was also determined.
RESULTS: Boys were more active than girls during recess. Girls engaged in more sedentary activity than boys. No main effects for ethnicity were observed. Children in grades 3 and 5 were more active than children in grades 4 and 6. Recess contributed 17.9% and 15.5% toward boys’ and girls’ school day moderate-to-vigorous physical activity, respectively.
CONCLUSION: Children engaged in physical activity during recess, though interventions may be needed to increase the intensity of activity in this context.

Agreement between activPAL and ActiGraph for assessing children's sedentary time

Background
Accelerometers have been used to determine the amount of time that children spend sedentary. However, as time spent sitting may be detrimental to health, research is needed to examine whether accelerometer sedentary cut-points reflect the amount of time children spend sitting. The aim of this study was to: a) examine agreement between ActiGraph (AG) cut-points for sedentary time and objectively-assessed periods of free-living sitting and sitting plus standing time using the activPAL (aP); and b) identify cut-points to determine time spent sitting and sitting plus standing.

Methods
Forty-eight children (54% boys) aged 8–12 years wore a waist-mounted AG and thigh-mounted aP for two consecutive school days (9–3:30 pm). AG data were analyzed using 17 cut-points between 50–850 counts·min−1 in 50 counts·min−1 increments to determine sedentary time during class-time, break time and school hours. Sitting and sitting plus standing time were obtained from the aP for these periods. Limits of agreement were computed to evaluate bias between AG50 to AG850 sedentary time and sitting and sitting plus standing time. Receiver Operator Characteristic (ROC) analyses identified AG cutpoints that maximized sensitivity and specificity for sitting and sitting plus standing time.

Results
The smallest mean bias between aP sitting time and AG sedentary time was AG150 for class time (3.8 minutes), AG50 for break time (−0.8 minutes), and AG100 for school hours (−5.2 minutes). For sitting plus standing time, the smallest bias was observed for AG850. ROC analyses revealed an optimal cut-point of 96 counts·min−1 (AUC = 0.75) for sitting time, which had acceptable sensitivity (71.7%) and specificity (67.8%). No optimal cut-point was obtained for sitting plus standing (AUC = 0.51).

Conclusions
Estimates of free-living sitting time in children during school hours can be obtained using an AG cut-point of 100 counts·min−1. Higher sedentary cut-points may capture both sitting and standing time.

Total and Appendicular Lean Mass Reference Ranges for Australian Men and Women: The Geelong Osteoporosis Study

The aim of this study was to develop reference ranges for total and appendicular lean mass measured using dual-energy X-ray absorptiometry (DXA) from a randomly selected population-based sample of men and women residing in southeastern Australia. Men (n = 1,411) and women (n = 960) aged 20–93 years, enrolled in the Geelong Osteoporosis Study, were randomly selected from the Barwon Statistical Division using the electoral roll as a sampling frame in 2001–2006 (67 % participation) and 1993–1997 (77 % participation), respectively. Using DXA (Lunar DPX-L or Prodigy Pro) at baseline for men and at the 10-year follow-up for women (2004–2008), total and appendicular lean mass were measured. Means and standard deviations for each lean mass measure (absolute and relative to height squared) were generated for each age decade, and cutpoints equivalent to T scores of −2.0 and −1.0 were calculated using data from young adult men and women aged 20–39 years. Young adult reference data were derived from 374 men and 308 women. Cutpoints for relative appendicular lean mass equal to T scores of −2.0 and −1.0 were 6.94 and 7.87 kg/m2 for men and 5.30 and 6.07 kg/m2 for women. The proportions of men and women aged ≥80 years with a T score less than −2.0 were 16.0 and 6.2 %, respectively. These reference ranges may be useful for identifying lean mass deficits in the assessment of muscle wasting and sarcopenia.

Equating accelerometer estimates among youth: The Rosetta Stone 2

Different accelerometer cutpoints used by different researchers often yields vastly different estimates of moderate-to-vigorous intensity physical activity (MVPA). This is recognized as cutpoint non-equivalence (CNE), which reduces the ability to accurately compare youth MVPA across studies. The objective of this research is to develop a cutpoint conversion system that standardizes minutes of MVPA for six different sets of published cutpoints.

Minimal disease activity for rheumatoid arthritis: A preliminary definition

Agreement on response criteria in rheumatoid arthritis (RA) has allowed better standardization and interpretation of clinical trial reports. With recent advances in therapy, the proportion of patients achieving a satisfactory state of minimal disease activity (MDA) is becoming a more important measure with which to compare different treatment strategies. The threshold for MDA is between high disease activity and remission and, by definition, anyone in remission will also be in MDA. True remission is still rare in RA; in addition, the American College of Rheumatology definition is difficult to apply in the context of trials. Participants at OMERACT 6 in 2002 agreed on a conceptual definition of minimal disease activity (MDA): "that state of disease activity deemed a useful target of treatment by both the patient and the physician, given current treatment possibilities and limitations." To prepare for a preliminary operational definition of MDA for use in clinical trials, we asked rheumatologists to assess 60 patient profiles describing real RA patients seen in routine clinical practice. Based on their responses, several candidate definitions for MDA were designed and discussed at the OMERACT 7 in 2004. Feedback from participants and additional on-site analyses in a cross-sectional database allowed the formulation of 2 preliminary, equivalent definitions of MDA: one based on the Disease Activity Score 28 (DAS28) index, and one based on meeting cutpoints in 5 out the 7 WHO/ILAR core set measures. Researchers applying these definitions first need to choose whether to use the DAS28 or the core set definition, because although each selects a similar proportion in a population, these are not always the same patients. In both MDA definitions, an initial decision node places all patients in MDA who have a tender joint count of 0 and a swollen joint count of 0, and an erythrocyte sedimentation rate (ESR) no greater than 10 mm. If this condition is not met: center dot The DAS28 definition places patients in MDA when DAS28

Morbidity patterns among the underweight, overweight and obese between 2 and 18 years: population-based cross-sectional analyses

CONTEXT: No study has documented how symptomatic morbidity varies across the body mass index (BMI) spectrum (underweight, normal weight, overweight and obese) or across the entire child and adolescent age range. OBJECTIVE: To (1) quantify physical and psychosocial morbidities experienced by 2-18-year-olds according to BMI status and (2) explore morbidity patterns by age. DESIGN, SETTING AND PARTICIPANTS: Cross-sectional data from two Australian population studies (the Longitudinal Study of Australian Children and the Health of Young Victorians Study) were collected during 2000-2006. Participants were grouped into five age bands: 2-3 (n=4606), 4-5 (n=4983), 6-7 (n=4464), 8-12 (n=1541) and 13-18 (n=928) years. MAIN MEASURES: Outcomes-Parent- and self-reported global health; physical, psychosocial and mental health; special health-care needs; wheeze; asthma and sleep problems. Exposure-measured BMI (kg m(-2)) categorised using standard international cutpoints. ANALYSES: The variation in comorbidities across BMI categories within and between age bands was examined using linear and logistic regression models. RESULTS: Comorbidities varied with BMI category for all except sleep problems, generally showing the highest levels for the obese category. However, patterns differed markedly between age groups. In particular, poorer global health and special health-care needs were associated with underweight in young children, but obesity in older children. Prevalence of poorer physical health varied little by BMI in 2-5-year-olds, but from 6 to 7 years was increasingly associated with obesity. Normal-weight children tended to experience the best psychosocial and mental health, with little evidence that the U-shaped associations of these variables with BMI status varied by age. Wheeze and asthma increased slightly with BMI at all ages. CONCLUSIONS: Deviation from normal weight is associated with health differences in children and adolescents that vary by morbidity and age. As well as lowering risks for later disease, promoting normal body weight appears central to improving the health and well-being of the young.

Handgrip strength cut-off for cardiometabolic risk index among Colombian children and adolescents : the FUPRECOL study

Abstract Objective: Evidence shows an association between muscular strength (MS) and health among youth, however low muscular strength cut-points for the detection of high metabolic risk in Latin-American populations are scarce. The aim of this study was two-fold: to explore potential age- and sex-specific thresholds of MS, for optimal cardiometabolic risk categorization among Colombian children and adolescents; and to investigate if cardiometabolic risk differed by MS group by applying the receiver operating characteristic curve (ROC) cut point. Methods: This is a secondary analysis of a cross-sectional study (the FUPRECOL study), published elsewhere. The FUPRECOL study assessments were conducted during the 2014– 2015 school year. MS was estimated by a handle dynamometer on 1,950 children and adolescents from Colombia, using the MS relative to weight (handgrip strength/body mass). A metabolic risk score was computed from the following components: waist circumference, triglycerides, HDL-c, glucose, systolic and diastolic blood pressure. ROC analysis showed a significant discriminatory accuracy of MS in identifying the low/high metabolic risk in children and adolescents and both gender. Results: In children, handgrip strength/body mass level for a low metabolic risk were 0.359 and 0.376 in girls and boys, respectively. In adolescents, these points were 0.440 and 0.447 in girls and boys, respectively. Conclusion: In conclusion, the results suggest a hypothetical MS level relative to weight for having a low metabolic risk, which could be used to identify youths at risk.