On the origin of obesity: identifying the biological, environmental and cultural drivers of genetic risk among human populations.

Genetic predisposition to obesity presents a paradox: how do genetic variants with a detrimental impact on human health persist through evolutionary time? Numerous hypotheses, such as the thrifty genotype hypothesis, attempt to explain this phenomenon yet fail to provide a justification for the modern obesity epidemic. In this critical review, we appraise existing theories explaining the evolutionary origins of obesity and explore novel biological and sociocultural agents of evolutionary change to help explain the modern-day distribution of obesity-predisposing variants. Genetic drift, acting as a form of 'blind justice,' may randomly affect allele frequencies across generations while gene pleiotropy and adaptations to diverse environments may explain the rise and subsequent selection of obesity risk alleles. As an adaptive response, epigenetic regulation of gene expression may impact the manifestation of genetic predisposition to obesity. Finally, exposure to malnutrition and disease epidemics in the wake of oppressive social systems, culturally mediated notions of attractiveness and desirability, and diverse mating systems may play a role in shaping the human genome. As an important first step towards the identification of important drivers of obesity gene evolution, this review may inform empirical research focused on testing evolutionary theories by way of population genetics and mathematical modelling.

Overweight, obesity and adiposity in survivors of childhood brain tumours: a systematic review and meta-analysis.

Survivors of childhood brain tumours (SCBT) have increased cardiometabolic risks, but the determinants of these risks are unclear. This systematic review aims to compare the prevalence of overweight and obesity as well as adiposity measures between SCBT and non-cancer controls. The PubMed, EMBASE, MEDLINE, CINAHL and the Cochrane Library databases were searched. The primary outcomes were the prevalence of overweight and obesity based on body mass index. The secondary outcomes were adiposity measures including percent fat mass, waist-to-hip and waist-to-height ratios. Forty-one studies were included in the meta-analysis. The prevalence of overweight and obesity combined was similar between overall SCBT, SCBT excluding craniopharyngioma and non-cancer controls (42.6%, 95% CI 30.1-55.1 vs. 31.7%, 95% CI 20.4-43.0 vs. 40.4%, 95% CI 34.0-46.8). We also found that SCBT have higher percent fat mass (mean difference 4.1%, 95% CI 2.0-6.1), waist-to-hip ratio (mean difference 0.07, 95% CI 0.02-0.13) and waist-to-height ratio (mean difference 0.06, 95% CI 0.01-0.10) than non-cancer controls. We conclude that SCBT have similar overweight and obesity distribution but higher adiposity than non-cancer controls. More studies were needed to explore the determinants of adiposity and its contribution to cardiometabolic outcomes in SCBT.

The effectiveness of interventions to treat hypothalamic obesity in survivors of childhood brain tumours: a systematic review.

BACKGROUND: Survivors of childhood brain tumours (SCBT) are at risk of type 2 diabetes and cardiovascular diseases. Obesity is a major driver of cardiometabolic diseases in the general population, and interventions that tackle obesity may lower the risk of these chronic diseases. The goal of this systematic review was to summarize current evidence for the presence of interventions to manage obesity, including hypothalamic obesity, in SCBT. METHODS: The primary outcome of this review was the body mass index z-score change from baseline to the end of the intervention and/or follow-up. Literature searches were conducted in PsycINFO, CINAHL, the Cochrane Library, Medline, SPORTDiscus, EMBASE and PubMed. Two reviewers completed study evaluations independently. RESULTS: Eleven publications were included in this systematic review (lifestyle intervention n = 2, pharmacotherapy n = 6 and bariatric surgery n = 3). While some studies demonstrated effectiveness of interventions to manage obesity in SCBT and alter markers of obesity and cardiometabolic risk, the evidence base was limited and of low quality, and studies focused on hypothalamic obesity. We conclude that there is urgent need to conduct adequately powered trials of sufficient duration, using existing and novel therapies to manage obesity, reduce the burden of cardiometabolic disorders and improve outcomes in SCBT.

Development and validation of a generic scale for use in transition programmes to measure self-management skills in adolescents with chronic health conditions: the TRANSITION-Q.

AIM: To develop a generic self-management skills scale for use with adolescents diagnosed with a chronic health condition who are aged 12 to 18 years. BACKGROUND: There is a lack of methodologically sound scales for healthcare teams to use to measure self-management skills in adolescents with chronic conditions transitioning to adult care. METHODS: Adolescents aged 12 to 18 years with a broad range of chronic health conditions, including neurodevelopmental conditions, were recruited from May to August 2013 from nine outpatient clinics at McMaster Children's Hospital (Canada). Thirty-two participated in a cognitive interview, and 337 completed a questionnaire booklet. Interviews were used to develop the TRANSITION-Q. Rasch measurement theory (RMT) analysis was used to identify items that represent the best indicators of self-management skills. Traditional psychometric tests of measurement performance were also conducted. RESULTS: The response rate was 92% (32/32 cognitive; 337/371 field test). RMT analysis resulted in a 14-item scale with three response options. The overall fit of the observed data to that expected by the Rasch model was non-significant, providing support that this new scale measured a unidimensional construct. Other tests supported the scale as scientifically sound, e.g. Person Separation Index = 0.82; good item fit statistics; no differential item function by age or gender; low residual correlations between items; Cronbach's alpha = 0.85; test-retest reliability = 0.90; and tests of construct validity that showed, as hypothesized, fewer skills in younger participants and in participants who required assistance to complete the scale. Finally, participants who agreed they are ready to transfer to adult healthcare reported higher TRANSITION-Q scores than did participants who disagreed. CONCLUSIONS: The TRANSITION-Q is a short, clinically meaningful and psychometrically sound scale. This generic scale can be used in research and in paediatric and adolescent clinics to help evaluate readiness for transition.

Doctors' and nurses' attitudes towards neonatal ethical decision making in Ireland.

OBJECTIVE: To explore the clinical staff attitudes towards ethical decision making in neonatal intensive care units (NICUs) in Ireland, to establish differences between doctors and nurses and to compare attitudes in Ireland with those in Europe. DESIGN: Cross-sectional study by means of an anonymous questionnaire. 64 doctors and 228 nurses in seven NICUs participated (response rates 74% and 81%, respectively). Through factor analysis the staff answers to 12 attitude statements were used to build a score whose range varied from 0 (preservation of life in any case) to 10, indicating a more individualised approach according to the patient's best interests. MAIN OUTCOME MEASURE: Staff attitudes to ethical decision making in NICU. RESULTS: Mean values of attitude scores were 5.8 (95% CI 5.3 to 6.2) for doctors, and 6.0 (95% CI 5.5 to 6.5) for nurses. Respondents with experience in follow-up of NICU graduates had significantly higher scores (6.7 vs 5.4, p = 0.018), while the opposite was true among more religious staff (5.8 vs 6.9, p = 0.026) and particularly for minority religions such as Muslim (4.1, 95% CI 3.1 to 5.2). Scores were higher after age 30 for nurses, and after age 40 for doctors, suggesting the adoption of a less vitalistic viewpoint as respondents grow older and more experienced. Among doctors, a relationship was found between the attitude score and their self-reported non-treatment practices. CONCLUSIONS: In Ireland, NICU doctors and nurses hold similar attitudes towards ethical decision making. Personal and professional factors have a statistically significant impact on attitude score. Compared with the rest of Europe, attitudes in Ireland appear more similar to those of southern rather than northern European countries.