Prognostic significance of absolute lymphocyte count in patients with metastatic renal cell carcinoma receiving first-line combination immunotherapies: results from the International Metastatic Renal Cell Carcinoma Database Consortium.

BACKGROUND: Lymphocytes are closely linked to mechanisms of action of immuno-oncology (IO) agents. We aimed to assess the prognostic significance of absolute lymphocyte count (ALC) in patients with metastatic renal cell carcinoma (mRCC). PATIENTS AND METHODS: Using the International mRCC Database Consortium (IMDC), patients receiving first-line IO-based combination therapy were analysed. Baseline patient characteristics, objective response rates (ORRs), time to next treatment (TTNT), and overall survival (OS) were compared. RESULTS: Of 966 patients included, 195 (20%) had lymphopenia at baseline, and they had a lower ORR (37% versus 45%; P < 0.001), shorter TTNT (10.1 months versus 24.3 months; P < 0.001), and shorter OS (30.4 months versus 48.2 months; P < 0.001). Among 125 patients with lymphopenia at baseline, 52 (42%) experienced ALC recovery at 3 months, and they had longer OS (not reached versus 30.4 months; P = 0.012). On multivariable analysis for OS, lymphopenia was an independent adverse prognostic factor (hazard ratio 1.68; P < 0.001). Incorporation of lymphopenia into the IMDC criteria improved OS prediction accuracy (C-index from 0.688 to 0.707). CONCLUSIONS: Lymphopenia was observed in one-fifth of treatment-naive patients with mRCC and may serve as an indicator of unfavourable oncologic outcomes in the contemporary IO era.

Generational trends in the transition to womanhood in lowland rural Nepal: Changes in the meaning of early marriage.

OBJECTIVE: In South Asia, studies show secular trends toward slightly later women's marriage and first reproduction. However, data on related biological and social events, such as menarche and age of coresidence with husband, are often missing from these analyses. We assessed generational trends in key life events marking the transition to womanhood in rural lowland Nepal. METHODS: We used data on 110 co-resident mother-in-law (MIL) and daughter-in-law (DIL) dyads. We used paired t-tests and chi-squared tests to evaluate generational trends in women's education, and mean age at menarche, marriage, cohabitation with husband, and first reproduction of MIL and DIL dyads. We examined norms held by MILs and DILs on a daughter's life opportunities. RESULTS: On average, MIL was 29 years older than DIL (60 years vs. 31 years). Both groups experienced menarche at average age 13.8 years. MIL was married at average 12.4 years, before menarche, and cohabitated with husbands at average 14.8 years. DIL was simultaneously married and cohabitated with husbands after menarche, at average 15 years. DIL was marginally more educated than MIL but had their first child on average 0.8 years earlier (95% CI -1.4, -0.1). MIL and DIL held similar norms on daughters' education and marriage. CONCLUSION: While social norms remain similar, the meaning of "early marriage" and use of menarche in marriage decisions has changed in rural lowland Nepal. Compared to DIL, MIL who was married earlier transitioned to womanhood more gradually. However, DIL was still married young, and had an accelerated trajectory to childbearing.

There is an obstetrical dilemma: Misconceptions about the evolution of human childbirth and pelvic form.

Compared to other primates, modern humans face high rates of maternal and neonatal morbidity and mortality during childbirth. Since the early 20th century, this "difficulty" of human parturition has prompted numerous evolutionary explanations, typically assuming antagonistic selective forces acting on maternal and fetal traits, which has been termed the "obstetrical dilemma." Recently, there has been a growing tendency among some anthropologists to question the difficulty of human childbirth and its evolutionary origin in an antagonistic selective regime. Partly, this stems from the motivation to combat increasing pathologization and overmedicalization of childbirth in industrialized countries. Some authors have argued that there is no obstetrical dilemma at all, and that the difficulty of childbirth mainly results from modern lifestyles and inappropriate and patriarchal obstetric practices. The failure of some studies to identify biomechanical and metabolic constraints on pelvic dimensions is sometimes interpreted as empirical support for discarding an obstetrical dilemma. Here we explain why these points are important but do not invalidate evolutionary explanations of human childbirth. We present robust empirical evidence and solid evolutionary theory supporting an obstetrical dilemma, yet one that is much more complex than originally conceived in the 20th century. We argue that evolutionary research does not hinder appropriate midwifery and obstetric care, nor does it promote negative views of female bodies. Understanding the evolutionary entanglement of biological and sociocultural factors underlying human childbirth can help us to understand individual variation in the risk factors of obstructed labor, and thus can contribute to more individualized maternal care.

Industry Funding of Oncology Randomised Controlled Trials: Implications for Design, Results and Interpretation.

AIMS: Most randomised controlled trials (RCTs) in oncology are now funded by the pharmaceutical industry. We explore the extent to which RCT design, results and interpretation differ between industry-funded and non-industry-funded RCTs. MATERIALS AND METHODS: In this cross-sectional analysis, a structured literature search was used to identify all oncology RCTs published globally during 2014-2017. Industry funding was identified based on explicit statements in the publication. Descriptive statistics were used to compare elements of trial methodology and output between industry- and non-industry-funded RCTs. RESULTS: The study sample included 694 RCTs; 71% were funded by industry. Industry-funded trials were more likely to test systemic therapy (97% versus 62%; P < 0.001), palliative-intent therapy (71% versus 41%; P < 0.001) and study breast cancer (20% versus 12%; P < 0.001). Industry-funded trials were larger (median sample size 474 versus 375; P < 0.001) and more likely to meet their primary end point (49% versus 41%; P < 0.001). Among positive trials, there were no differences in the magnitude of benefit between industry- and non-industry-funded RCTs. Trials funded by industry were published in journals that had a significantly higher median impact factor (21, interquartile range 7, 28) than non-industry-funded trials (impact factor 12, interquartile range 5, 24; P = 0.005); this persisted when adjusted for whether a trial was positive or negative. CONCLUSIONS: The vast majority of oncology RCTs are now funded by industry. Industry-funded trials are larger, more likely to be positive, predominantly test systemic therapies in the palliative setting and are published in higher impact journals than trials without industry support.

The impact of the Covid-19 lockdown on the experiences and feeding practices of new mothers in the UK: Preliminary data from the COVID-19 New Mum Study.

BACKGROUND: The COVID-19 New Mum Study is recording maternal experiences and infant feeding during the UK lockdown. This report from week 1 of the survey describes and compares the delivery and post-natal experiences of women who delivered before (BL) versus during (DL) the lockdown. METHODS: Women living in the UK aged ≥18 years with an infant ≤12 months of age completed an anonymous online survey (https://is.gd/covid19newmumstudy). Information/links are shared via websites, social media and existing contacts. RESULTS: From 27.5.20-3.6.20, 1365 women provided data (94% white, 95% married/with partner, 66% degree/higher qualification, 86% living in house; 1049 (77%) delivered BL and 316 (23%) DL. Delivery mode, skin-to-skin contact and breastfeeding initiation did not differ between groups. DL women had shorter hospital stays (p < 0.001). 39% reported changes to their birth plan. Reflecting younger infant age, 59% of DL infants were exclusively breast-fed/mixed fed versus 39% of BL (p < 0.05). 13% reported a change in feeding; often related to lack of breastfeeding support, especially with practical problems. Important sources of feeding support were the partner (60%), health professional (50%) and online groups (47%). 45% of DL women reported insufficient feeding support. Among BL women, 57% and 69% reported decreased feeding support and childcare, respectively. 40% BL/45% DL women reported insufficient support with their own health, 8%/9% contacted a mental health professional; 11% reported their mental health was affected. 9% highlighted lack of contact/support from family and distress that they had missed seeing the baby. CONCLUSION: Lockdown has impacted maternal experiences, resulting in distress for many women. Our findings suggest the need for better infant feeding support, especially 'face-to-face' support for practical issues; and recognising and supporting mothers who are struggling with mental health challenges or other aspects of their health. The effectiveness of online versus face-to-face contact is currently uncertain, and requires further evaluation.

Bioelectric impedance vector analysis (BIVA) in hospitalised children; predictors and associations with clinical outcomes.

BACKGROUND: Clinical use of bioelectric impedance is limited by variability in hydration. Analysis of raw bioelectric impedance vectors (BIVA), resistance (R), reactance (Xc) and phase angle (PA) may be an alternative for monitoring disease progression/treatment. Clinical experience of BIVA in children is limited. We investigated predictors of BIVA and their ability to predict clinical outcomes in children with complex diagnoses. METHODS: R, Xc and PA were measured (BODYSTAT Quadscan 4000) on admission in 108 patients (4.6-16.8 years, mean 10.0). R and Xc were indexed by height (H) and BIVA-SDS for age and sex calculated using data from healthy children. Potential predictors and clinical outcomes (greater-than-expected length-of-stay (LOS), complications) were recorded. RESULTS: Mean R/H-SDS was significantly higher (0.99 (SD 1.32)) and PA-SDS lower (-1.22 (1.68))) than expected, with a wide range for all parameters. In multivariate models, the Strongkids risk category predicted R/H-SDS (adjusted mean for low, medium and high risk = 0.49, 1.28, 2.17, p = 0.009) and PA-SDS (adjusted mean -0.52, -1.53, -2.36, p = 0.01). BIVA-SDS were not significantly different in patients with or without adverse outcomes. CONCLUSIONS: These complex patients had abnormal mean BIVA-SDS suggestive of reduced hydration and poor cellular health according to conventional interpretation. R/H-SDS was higher and PA-SDS lower in those classified as higher malnutrition risk by the StrongKids tool. Further investigation in specific patient groups, including those with acute fluid shifts and using disease-specific outcomes, may better define the clinical role of BIV.

Real-world outcomes of nivolumab and cabozantinib in metastatic renal cell carcinoma: results from the International Metastatic Renal Cell Carcinoma Database Consortium.

Objectives: In the present study, we explored the real-world efficacy of the immuno-oncology checkpoint inhibitor nivolumab and the tyrosine kinase inhibitor cabozantinib in the second-line setting. Methods: Using the International Metastatic Renal Cell Carcinoma Database Consortium (imdc) dataset, a retrospective analysis of patients with metastatic renal cell carcinoma (mrcc) treated with nivolumab or cabozantinib in the second line after prior therapy targeted to the vascular endothelial growth factor receptor (vegfr) was performed. Baseline characteristics and imdc risk factors were collected. Overall survival (os) and time to treatment failure (ttf) were calculated using Kaplan-Meier curves. Overall response rates (orrs) were determined for each therapy. Multivariable Cox regression analysis was performed to determine survival differences between cabozantinib and nivolumab treatment. Results: The analysis included 225 patients treated with nivolumab and 53 treated with cabozantinib. No significant difference in median os was observed: 22.10 months [95% confidence interval (ci): 17.18 months to not reached] with nivolumab and 23.70 months (95% ci: 15.52 months to not reached) with cabozantinib (p = 0.61). The ttf was also similar at 6.90 months (95% ci: 4.60 months to 9.20 months) with nivolumab and 7.39 months (95% ci: 5.52 months to 12.85 months) with cabozantinib (p = 0.20). The adjusted hazard ratio (hr) for nivolumab compared with cabozantinib was 1.30 (95% ci: 0.73 to 2.3), p = 0.38. When adjusted by imdc criteria and age, the hr was 1.32 (95% ci: 0.74 to 2.38), p = 0.35. Conclusions: Real-world imdc data indicate comparable os and ttf for nivolumab and cabozantinib. Both agents are reasonable therapeutic options for patients progressing after initial first-line vegfr-targeted therapy.

Patterns of childhood body mass index (BMI), overweight and obesity in South Asian and black participants in the English National child measurement programme: effect of applying BMI adjustments standardising for ethnic differences in BMI-body fatness associations.

BACKGROUND: The National Child Measurement Programme (NCMP) records weight and height and assesses overweight-obesity patterns in English children using body mass index (BMI), which tends to underestimate body fatness in South Asian children and overestimate body fatness in Black children of presumed African ethnicity. Using BMI adjustments to ensure that adjusted BMI was similarly related to body fatness in South Asian, Black and White children, we reassessed population overweight and obesity patterns in these ethnic groups in NCMP. METHODS: Analyses were based on 2012-2013 NCMP data in 582 899 children aged 4-5 years and 485 362 children aged 10-11 years. Standard centile-based approaches defined weight status in each age group before and after applying BMI adjustments for English South Asian and Black children derived from previous studies using the deuterium dilution method. FINDINGS: Among White children, overweight-obesity prevalences (boys, girls) were 23% and 21%, respectively, in 4-5 year olds and 33% and 30%, respectively, in 10-11 year olds. Before adjustment, South Asian children had lower overweight-obesity prevalences at 4-5 years (19%, 19%) and slightly higher prevalences at 10-11 years (42%, 34%), whereas Black children had higher overweight-obesity prevalences both at 4-5 years (31%, 29%) and 10-11 years (42%, 45%). Following adjustment, overweight-obesity prevalences were markedly higher in South Asian children both at 4-5 years (39%, 35%) and at 10-11 years (52%, 44%), whereas Black children had lower prevalences at 4-5 years (11%, 12%); at 10-11 years, prevalences were slightly lower in boys (32%) but higher in girls (35%). INTERPRETATION: BMI adjustments revealed extremely high overweight-obesity prevalences among South Asian children in England, which were not apparent in unadjusted data. In contrast, after adjustment, Black children had lower overweight-obesity prevalences except among older girls. FUNDING: British Heart Foundation, NIHR CLAHRC (South London), NIHR CLAHRC (North Thames).

Relation between body composition at birth and child development at 2 years of age: a prospective cohort study among Ethiopian children.

BACKGROUND/OBJECTIVES: Birth weight (BW), independent of socioeconomic status, has been identified as a predictor for childhood cognitive development. However, it is not known whether this relation is related to low BW per se or particularly related to a deficit in fat mass (FM) or fat-free mass (FFM) at birth. This study therefore aimed at investigating the relation between body composition at birth and child development at 2 years of age. SUBJECTS/METHODS: An Ethiopian birth cohort was followed up at 2 years. Body composition was measured within 48 h of birth using infant air-displacement plethysmography. Child development was assessed at 2 years of age using Denver developmental screening test. Associations between body composition at birth and development at 2 years of age were tested using linear regression analysis. RESULTS: FFM but not FM at birth was positively associated with higher global developmental score at 2 years of age (ß=2.48, 95% confidence interval (CI) 0.17; 4.79) adjusted for neonatal, postnatal and parental characteristics. This association was attributable to the association with the language developmental domain (ß=1.61, 95 CI 0.33; 2.90). CONCLUSIONS: Among Ethiopian children, FFM at birth but not FM predicted better global and language development at 2 years of age. Higher FFM at birth might have exerted a positive effect on the growth and differentiation of the brain and neuronal circuits for better development. This study therefore highlights the need to improve mother's nutritional status during pregnancy in ways that stimulate fetal FFM growth.

Body mass index adjustments to increase the validity of body fatness assessment in UK Black African and South Asian children.

BACKGROUND/OBJECTIVES: Body mass index (BMI) (weight per height2) is the most widely used marker of childhood obesity and total body fatness (BF). However, its validity is limited, especially in children of South Asian and Black African origins. We aimed to quantify BMI adjustments needed for UK children of Black African and South Asian origins so that adjusted BMI related to BF in the same way as for White European children. METHODS: We used data from four recent UK studies that made deuterium dilution BF measurements in UK children of White European, South Asian and Black African origins. A height-standardized fat mass index (FMI) was derived to represent BF. Linear regression models were then fitted, separately for boys and girls, to quantify ethnic differences in BMI-FMI relationships and to provide ethnic-specific BMI adjustments. RESULTS: We restricted analyses to 4-12 year olds, to whom a single consistent FMI (fat mass per height5) could be applied. BMI consistently underestimated BF in South Asians, requiring positive BMI adjustments of +1.12 kg m-2 (95% confidence interval (CI): 0.83, 1.41 kg m-2; P<0.0001) for boys and +1.07 kg m-2 (95% CI: 0.74, 1.39 kg m-2; P<0.0001) for girls of all age groups and FMI levels. BMI overestimated BF in Black Africans, requiring negative BMI adjustments for Black African children. However, these were complex because there were statistically significant interactions between Black African ethnicity and FMI (P=0.004 boys; P=0.003 girls) and also between FMI and age group (P<0.0001 for boys and girls). BMI adjustments therefore varied by age group and FMI level (and indirectly BMI); the largest adjustments were in younger children with higher unadjusted BMI and the smallest in older children with lower unadjusted BMI. CONCLUSIONS: BMI underestimated BF in South Asians and overestimated BF in Black Africans. Ethnic-specific adjustments, increasing BMI in South Asians and reducing BMI in Black Africans, can improve the accuracy of BF assessment in these children.

Body composition and susceptibility to type 2 diabetes: an evolutionary perspective.

Type 2 diabetes is rapidly increasing in prevalence worldwide, in concert with epidemics of obesity and sedentary behavior that are themselves tracking economic development. Within this broad pattern, susceptibility to diabetes varies substantially in association with ethnicity and nutritional exposures through the life-course. An evolutionary perspective may help understand why humans are so prone to this condition in modern environments, and why this risk is unequally distributed. A simple conceptual model treats diabetes risk as the function of two interacting traits, namely 'metabolic capacity' which promotes glucose homeostasis, and 'metabolic load' which challenges glucose homoeostasis. This conceptual model helps understand how long-term and more recent trends in body composition can be considered to have shaped variability in diabetes risk. Hominin evolution appears to have continued a broader trend evident in primates, towards lower levels of muscularity. In addition, hominins developed higher levels of body fatness, especially in females in relative terms. These traits most likely evolved as part of a broader reorganization of human life history traits in response to growing levels of ecological instability, enabling both survival during tough periods and reproduction during bountiful periods. Since the emergence of Homo sapiens, populations have diverged in body composition in association with geographical setting and local ecological stresses. These long-term trends in both metabolic capacity and adiposity help explain the overall susceptibility of humans to diabetes in ways that are similar to, and exacerbated by, the effects of nutritional exposures during the life-course.

European Pain Federation position paper on appropriate opioid use in chronic pain management.

Poorly controlled pain is a global public health issue. The personal, familial and societal costs are immeasurable. Only a minority of European patients have access to a comprehensive specialist pain clinic. More commonly the responsibility for chronic pain management and initiating opioid therapy rests with the primary care physician and other non-specialist opioid prescribers. There is much confusing and conflicting information available to non-specialist prescribers regarding opioid therapy and a great deal of unjustified fear is generated. Opioid therapy should only be initiated by competent clinicians as part of a multi-faceted treatment programme in circumstances where more simple measures have failed. Throughout, all patients must be kept under close clinical surveillance. As with any other medical therapy, if the treatment fails to yield the desired results and/or the patient is additionally burdened by an unacceptable level of adverse effects, the overall management strategy must be reviewed and revised. No responsible clinician will wish to pursue a failed treatment strategy or persist with an ineffective and burdensome treatment. In a considered attempt to empower and inform non-specialist opioid prescribers, EFIC convened a European group of experts, drawn from a diverse range of basic science and relevant clinical disciplines, to prepare a position paper on appropriate opioid use in chronic pain. The expert panel reviewed the available literature and harnessed the experience of many years of clinical practice to produce these series of recommendations. Its success will be judged on the extent to which it contributes to an improved pain management experience for chronic pain patients across Europe. SIGNIFICANCE: This position paper provides expert recommendations for primary care physicians and other non- specialist healthcare professionals in Europe, particularly those who do not have ready access to specialists in pain medicine, on the safe and appropriate use of opioid medications as part of a multi-faceted approach to pain management, in properly selected and supervised patients.

Association between Birth Interval and Cardiovascular Outcomes at 30 Years of Age: A Prospective Cohort Study from Brazil.

BACKGROUND: Birth interval is an important and potentially modifiable factor that is associated with child health. Whether an association exists with longer-term outcomes in adults is less well known. METHODS: Using the 1982 Pelotas (Brazil) Birth Cohort Study, the association of birth interval with markers of cardiovascular health at 30 years of age was examined. Multivariable linear regression was used with birth interval as a continuous variable and categorical variable, and effect modification by gender was explored. RESULTS: Birth interval and cardiovascular data were present for 2,239 individuals. With birth interval as a continuous variable, no association was found but stratification by gender tended to show stronger associations for girls. When compared to birth intervals of <18 months, as binary variable, longer intervals were associated with increases in height (1.6 cm; 95% CI: 0.5, 2.8) and lean mass (1.7 kg; 95% CI: 0.2, 3.2). No difference was seen with other cardiovascular outcomes. CONCLUSIONS: An association was generally not found between birth interval and cardiovascular outcomes at 30 years of age, though some evidence existed for differences between males and females and for an association with height and lean mass for birth intervals of 18 months and longer.

Body shape and size in 6-year old children: assessment by three-dimensional photonic scanning.

BACKGROUND: Body shape and size are typically described using measures such as body mass index (BMI) and waist circumference, which predict disease risks in adults. However, this approach may underestimate the true variability in childhood body shape and size. OBJECTIVE: To use a comprehensive three-dimensional photonic scan approach to describe variation in childhood body shape and size. SUBJECTS/METHODS: At age 6 years, 3350 children from the population-based 2004 Pelotas birth cohort study were assessed by three-dimensional photonic scanner, traditional anthropometry and dual X-ray absorptiometry. Principal component analysis (PCA) was performed on height and 24 photonic scan variables (circumferences, lengths/widths, volumes and surface areas). RESULTS: PCA identified four independent components of children's body shape and size, which we termed: Corpulence, Central:peripheral ratio, Height and arm lengths, and Shoulder diameter. Corpulence showed strong correlations with traditional anthropometric and body composition measures (r>0.90 with weight, BMI, waist circumference and fat mass; r>0.70 with height, lean mass and bone mass); in contrast, the other three components showed weak or moderate correlations with those measures (all r<0.45). There was no sex difference in Corpulence, but boys had higher Central:peripheral ratio, Height and arm lengths and Shoulder diameter values than girls. Furthermore, children with low birth weight had lower Corpulence and Height and arm lengths but higher Central:peripheral ratio and Shoulder diameter than other children. Children from high socio-economic position (SEP) families had higher Corpulence and Height and arm lengths than other children. Finally, white children had higher Corpulence and Central:peripheral ratio than mixed or black children. CONCLUSIONS: Comprehensive assessment by three-dimensional photonic scanning identified components of childhood body shape and size not captured by traditional anthropometry or body composition measures. Differences in these novel components by sex, birth weight, SEP and skin colour may indicate their potential relevance to disease risks.

Associations of gender inequality with child malnutrition and mortality across 96 countries.

National efforts to reduce low birth weight (LBW) and child malnutrition and mortality prioritise economic growth. However, this may be ineffective, while rising gross domestic product (GDP) also imposes health costs, such as obesity and non-communicable disease. There is a need to identify other potential routes for improving child health. We investigated associations of the Gender Inequality Index (GII), a national marker of women's disadvantages in reproductive health, empowerment and labour market participation, with the prevalence of LBW, child malnutrition (stunting and wasting) and mortality under 5 years in 96 countries, adjusting for national GDP. The GII displaced GDP as a predictor of LBW, explaining 36% of the variance. Independent of GDP, the GII explained 10% of the variance in wasting and stunting and 41% of the variance in child mortality. Simulations indicated that reducing GII could lead to major reductions in LBW, child malnutrition and mortality in low- and middle-income countries. Independent of national wealth, reducing women's disempowerment relative to men may reduce LBW and promote child nutritional status and survival. Longitudinal studies are now needed to evaluate the impact of efforts to reduce societal gender inequality.

Body composition and the monitoring of non-communicable chronic disease risk.

There is a need for simple proxies of health status, in order to improve monitoring of chronic disease risk within and between populations, and to assess the efficacy of public health interventions as well as clinical management. This review discusses how, building on recent research findings, body composition outcomes may contribute to this effort. Traditionally, body mass index has been widely used as the primary index of nutritional status in children and adults, but it has several limitations. We propose that combining information on two generic traits, indexing both the 'metabolic load' that increases chronic non-communicable disease risk, and the homeostatic 'metabolic capacity' that protects against these diseases, offers a new opportunity to improve assessment of disease risk. Importantly, this approach may improve the ability to take into account ethnic variability in chronic disease risk. This approach could be applied using simple measurements readily carried out in the home or community, making it ideal for M-health and E-health monitoring strategies.

Windows of opportunity for physical activity in the prevention of obesity.

Tackling increasing rates of obesity is likely to be a defining feature of health care over the next several decades. Adult obesity is a persistent and treatment-resistant problem. Consequently, an emerging theme in the literature is to commence prevention efforts earlier in the developmental time course. This view is based primarily on epidemiological data demonstrating a link between traits manifesting early during development and increased obesity risk in adulthood. Physical activity is a perennial factor in discussions of obesity prevention. However, the optimal timing and type of physical activity interventions to commence remains unclear. Critical developmental windows of plasticity may afford time-limited opportunities to shape body composition across the life course; however, physical activity has not been explicitly considered in these discussions. Although animal models suggest that physical activity commenced earlier in development has differential effects on obesity onset compared to physical activity commenced in adulthood, human research is lacking. In this conceptual review, we consider physical activity during critical developmental periods as a way to mitigate obesity risk later in life.

Body composition in young female eating-disorder patients with severe weight loss and controls: evidence from the four-component model and evaluation of DXA.

BACKGROUND/OBJECTIVES: Whether fat-free mass (FFM) and its components are depleted in eating-disorder (ED) patients is uncertain. Dual energy X-ray absorptiometry (DXA) is widely used to assess body composition in pediatric ED patients; however, its accuracy in underweight populations remains unknown. We aimed (1) to assess body composition of young females with ED involving substantial weight loss, relative to healthy controls using the four-component (4C) model, and (2) to explore the validity of DXA body composition assessment in ED patients. SUBJECTS/METHODS: Body composition of 13 females with ED and 117 controls, aged 10-18 years, was investigated using the 4C model. Accuracy of DXA for estimation of FFM and fat mass (FM) was tested using the approach of Bland and Altman. RESULTS: Adjusting for age, height and pubertal stage, ED patients had significantly lower whole-body FM, FFM, protein mass (PM) and mineral mass (MM) compared with controls. Trunk and limb FM and limb lean soft tissue were significantly lower in ED patients. However, no significant difference in the hydration of FFM was detected. Compared with the 4C model, DXA overestimated FM by 5 ± 36% and underestimated FFM by 1 ± 9% in ED patients. CONCLUSION: Our study confirms that ED patients are depleted not only in FM but also in FFM, PM and MM. DXA has limitations for estimating body composition in individual young female ED patients.

Calibration of bioelectrical impedance analysis for body composition assessment in Ethiopian infants using air-displacement plethysmography.

BACKGROUND/OBJECTIVES: Assessment of infant body composition (BC) is crucial to understand the consequences of suboptimal nutritional status and postnatal growth, and the effects of public health interventions. Bioelectrical impedance analysis (BIA) is a feasible, relatively inexpensive and noninvasive method for assessing BC. However, very little research has been conducted in low- and middle-income populations, where efforts to prevent or treat malnutrition in early life are a public health priority. We aimed to develop equations for predicting fat-free mass (FFM) and fat mass (FM) based on BIA in 0- to 6-month-old Ethiopian infants. SUBJECTS/METHODS: The study comprised a total of 186 BC assessments performed in 101 healthy infants, delivered at Jimma University Specialized Hospital. Infant air-displacement plethysmography (IADP) was the criterion method, whereas weight, length, sex, age and an impedance index (L(2)/Z50) were predictors. Prediction equations were developed using stepwise multiple linear regression and the accuracy was evaluated with a 10-fold cross-validation approach. RESULTS: A linear regression model based on body weight, age and sex predicted FFM, estimated by IADP, with an adjusted R(2) and root mean square error (RMSE) of 0.94 and 200 g, respectively. Adding impedance index to the model resulted in a significantly improved model fit (R(2)=0.95; RMSE=181 g). For infants below 3 months of age, inclusion of impedance index did not contribute to an improved model fit for predicting FFM compared with a model already comprising weight, sex and age. CONCLUSIONS: The derived equations predicted FFM with acceptable accuracy and may be used in future field surveys, epidemiological studies and clinical trials conducted in similar sub-Saharan African population groups aged 0-6 months.