Ringgold County Early Childhood Iowa Area independent auditor's reports, basic financial statements, schedule of findings, June 30, 2012

Audit report on the Ringgold County Early Childhood Iowa Area for the year ended June 30, 2012

Do childhood cancer survivors with physical performance limitations reach healthy activity levels?

BACKGROUND: The extent to which physical performance limitations affect the ability of childhood cancer survivors to reach healthy activity levels is unknown. Therefore this study aims to describe the effect of different types of limitations on activity levels in survivors. PROCEDURE: Within the Swiss Childhood Cancer Survivor Study we sent a questionnaire to all survivors (≥16 years) registered in the Swiss Childhood Cancer Registry, who survived >5 years and were diagnosed 1976-2005 aged <16 years. We measured healthy activity levels using international guidelines and assessed different kinds of performance limitations (visual impairment, weight and endurance problems, cardiorespiratory, musculoskeletal, and neurological problems, pain and fatigue syndromes). RESULTS: The sample included 1,560 survivors (75% response rate), of whom 209 (13.5%) reported they have performance limitations. Forty-two percent of survivors with limitations reached healthy activity levels, compared to 57% of survivors without limitations. Least active were survivors with vision impairments (25% active), weight and endurance problems (27.3%), cardiorespiratory problems (36.4%), and musculoskeletal problems (43.1%). After adjusting for socio-demographic variables and type of cancer, we found that survivors with limitations were 1.4 (95%CI 1.0-2.0; P = 0.047) times more likely to be inactive. CONCLUSIONS: Although many survivors with physical performance limitations maintain healthy activity levels, there is room for improvement. Adapted and targeted physical activity counseling for survivors with performance limitations might help them to raise level of activity and pursue a healthy lifestyle.

Audit report on the Taylor County Early Childhood Iowa Area for the year ended June 30, 2012

Audit report on the Taylor County Early Childhood Iowa Area for the year ended June 30, 2012

A common biological basis of obesity and nicotine addiction.

Smoking influences body weight such that smokers weigh less than non-smokers and smoking cessation often leads to weight increase. The relationship between body weight and smoking is partly explained by the effect of nicotine on appetite and metabolism. However, the brain reward system is involved in the control of the intake of both food and tobacco. We evaluated the effect of single-nucleotide polymorphisms (SNPs) affecting body mass index (BMI) on smoking behavior, and tested the 32 SNPs identified in a meta-analysis for association with two smoking phenotypes, smoking initiation (SI) and the number of cigarettes smoked per day (CPD) in an Icelandic sample (N=34,216 smokers). Combined according to their effect on BMI, the SNPs correlate with both SI (r=0.019, P=0.00054) and CPD (r=0.032, P=8.0 × 10(-7)). These findings replicate in a second large data set (N=127,274, thereof 76,242 smokers) for both SI (P=1.2 × 10(-5)) and CPD (P=9.3 × 10(-5)). Notably, the variant most strongly associated with BMI (rs1558902-A in FTO) did not associate with smoking behavior. The association with smoking behavior is not due to the effect of the SNPs on BMI. Our results strongly point to a common biological basis of the regulation of our appetite for tobacco and food, and thus the vulnerability to nicotine addiction and obesity.

Underdiagnosed and undertreated: obesity in the portuguese population.

Comment on: Post RE, Mainous AG 3rd, Gregorie SH, Knoll ME, Diaz VA, Saxena SK. The influence of physician acknowledgment of patients' weight status on patient perceptions of overweight and obesity in the United States. Arch Intern Med. 2011 Feb 28;171(4):316-21. PMID: 21357807.

Misconceptions about fructose-containing sugars and their role in the obesity epidemic.

A causal role of fructose intake in the aetiology of the global obesity epidemic has been proposed in recent years. This proposition, however, rests on controversial interpretations of two distinct lines of research. On one hand, in mechanistic intervention studies, detrimental metabolic effects have been observed after excessive isolated fructose intakes in animals and human subjects. On the other hand, food disappearance data indicate that fructose consumption from added sugars has increased over the past decades and paralleled the increase in obesity. Both lines of research are presently insufficient to demonstrate a causal role of fructose in metabolic diseases, however. Most mechanistic intervention studies were performed on subjects fed large amounts of pure fructose, while fructose is ordinarily ingested together with glucose. The use of food disappearance data does not accurately reflect food consumption, and hence cannot be used as evidence of a causal link between fructose intake and obesity. Based on a thorough review of the literature, we demonstrate that fructose, as commonly consumed in mixed carbohydrate sources, does not exert specific metabolic effects that can account for an increase in body weight. Consequently, public health recommendations and policies aiming at reducing fructose consumption only, without additional diet and lifestyle targets, would be disputable and impractical. Although the available evidence indicates that the consumption of sugar-sweetened beverages is associated with body-weight gain, and it may be that fructose is among the main constituents of these beverages, energy overconsumption is much more important to consider in terms of the obesity epidemic.

Energy expenditure and postprandial thermogenesis in obese women before and after weight loss.

In six young obese women (mean weight 85 +/- 3 kg) with a childhood history of obesity, and in six young nonobese women (mean weight 55 +/- 2 kg), the energy expenditure was measured during 24 h in a respiratory chamber with a maintenance energy intake. The next day, the thermogenic response to a mixed meal was investigated by using an open circuit indirect calorimetry hood system. In addition, five of the same obese women were similarly studied after a mean weight loss of 12.1 kg (14% of initial body weight) consecutive to an 11-wk hypocaloric diet (protein-supplemented modified fast). Expressed in absolute terms, the total 24 h and basal energy expenditures were found to be significantly greater in the obese (2208 +/- 105 and 1661 +/- 56 kcal/24 h, respectively) than in the controls (1746 +/- 61 and 1230 +/- 40 kcal/24 h, respectively). After weight loss, both the total 24-h and the basal energy expenditures were significantly reduced (2009 +/- 99 kcal/24 h and 1423 +/- 43 kcal/24 h respectively), but both values were still greater than that of the control subjects. The thermogenic response to the mixed meal (a liquid diet containing 17, 54, and 29% as protein, carbohydrate, and lipid calories, respectively, and an energy level determined to cover 60% of the basal energy expenditure computed for 24 h) was found to be significantly reduced in the obese as compared to controls (ie, 7.6 +/- 0.4% versus 9.5 +/- 0.4% of the energy content of the load, respectively, p less than 0.025). After weight loss, the postprandial thermogenesis of the obese was still markedly reduced (ie, 6.2 +/- 0.8%). Both before and after weight loss, the relative increase in diurnal urinary norepinephrine excretion was found to be lower in the obese than in controls, when compared to the nocturnal values. These results show that the greater 24 h energy expenditure of obese women is entirely due to their higher basal metabolic rate. The lower thermogenic response to the meal in the obese supports the concept of a thermogenic defect which can favor energy gain; furthermore, the unchanged response after weight loss in the obese suggests that the thermogenic defect may be a cause rather than a consequence of obesity.

Prevalence of obesity and abdominal obesity in the Lausanne population.

BACKGROUND: Obesity can be defined using body mass index (BMI) or waist (abdominal obesity). Little information exists regarding its prevalence and determinants in Switzerland. Hence, we assessed the levels of obesity as defined by BMI or waist circumference in a Swiss population-based sample. METHODS: Cross-sectional, population-based non-stratified random sample of 3,249 women and 2,937 men aged 35-75 years living in Lausanne, Switzerland. Overall participation rate was 41%. RESULTS: In men, the prevalences of overweight (BMI > or =25 kg/m2) and obesity (BMI > or =30 kg/m2) were 45.5% and 16.9%, respectively, higher than in women (28.3% and 14.3%, respectively). The prevalence of abdominal obesity (waist > or =102 in men and > or =88 cm in women) was higher in women than in men (30.6% vs. 23.9%). Obesity and abdominal obesity increased with age and decreased with higher educational level in both genders. In women, the prevalence of obesity was lower among former and current smokers, whereas in men the prevalence of obesity was higher in former smokers but did not differ between current and never smokers. Multivariate analysis showed age to be positively related, and education and physical activity to be negatively related with obesity and abdominal obesity in both genders, whereas differential effects of smoking were found between genders. CONCLUSION: The prevalence of abdominal obesity is higher than BMI-derived obesity in the Swiss population. Women presented with more abdominal obesity than men. The association between smoking and obesity levels appears to differ between genders.

Direct Effect of Birth Weight on Childhood Blood Pressure: a Causal Mediation Analysis

Background: Numerous studies have shown a negative association between birth weight (BW) and blood pressure (BP) later in life. To estimate the direct effect of BW on BP, it is conventional to condition on current weight (CW). However, such conditioning can induce collider stratification bias in the estimate of the direct effect. Objective: To bound the potential bias due to U, an unmeasured common cause of CW and BP, on the estimate of the (controlled) direct effect of BW on BP. Methods: Data from a school based study in Switzerland were used (N = 4,005; 2,010 B/1,995 G; mean age: 12.3 yr [range: 10.1-14.9]). Measured common causes of BW-BP (SES, smoking, body weight, and hypertension status of the mother) and CW-BP (breastfeeding and child's physical activity and diet) were identified with DAGs. Linear regression models were fitted to estimate the association between BW and BP. Sensitivity analyses were conducted to assess the potential effect of U on the association between BW and BP. U was assumed 1) to be a binary variable that affected BP by the same magnitude in low BWand in normal BW children and 2) to have a different prevalence in low BW children and in normal BW children for a given CW. Results: A small negative association was observed between BW and BP [beta: -0.3 mmHg/kg (95% CI: -0.9 to 0.3)]. The association was strengthened upon conditioning for CW [beta: -1.5 mmHg/kg (95% CI: -2.1 to -0.9)]. Upon further conditioning on common causes of BW-BP and CW-BP, the association did not change substantially [beta: -1.4 mmHg/kg (95% CI: -2.0 to -0.8)]. The negative association could be explained by U only if U was strongly associated with BP and if there was a large difference in the prevalence of U between low BWand normal BW children. Conclusion: The observed negative association between BW and BP upon adjustment for CW was not easily explained by an unmeasured common cause of CWand BP.

Prevalence of normal weight obesity in Switzerland: effect of various definitions

BACKGROUND: Normal weight obesity (NWO) is defined as an excessive body fat associated with a normal body mass index (BMI < 25 kg/m(2)), but its prevalence in the general population is unknown. AIM OF THE STUDY: To assess the prevalence of NWO in Switzerland according to different cut points used to define excess body fat. METHODS: Cross-sectional study including 3,213 women and 2,912 men aged 35-75 years. Body fat was assessed by bioelectrical impedance analysis and prevalence of NWO was assessed using four previously published definitions for excess body fat. RESULTS: Percent body fat increased with age: in men, the values (mean +/- SD) were 20.2 +/- 5.4, 23.0 +/- 5.4, 26.3 +/- 5.2 and 28.2 +/- 4.6 for age groups 35-44, 45-54, 55-64 and 65-75 years, respectively; the corresponding values for women were 29.9 +/- 7.8, 33.1 +/- 7.4, 36.7 +/- 7.5 and 39.6 +/- 6.9. In men, prevalence of NWO was <1% irrespective of the definition used. Conversely, in women, a 1- to 20-fold difference (from 1.4 to 27.8%) in NWO prevalence was found. The prevalence of NWO increased with age when age-independent cut points were used in women, but not in men. CONCLUSIONS: Prevalence of NWO is low in the general population and higher in women than in men. The prevalence is highly dependent on the criteria used to define excess body fat, namely in women. The use of gender- and age-specific cut points to define excess body fat is better than fixed or gender-specific only cut points.

A Mutation in CALM1 Encoding Calmodulin in Familial Idiopathic Ventricular Fibrillation in Childhood and Adolescence.

OBJECTIVES: This study aimed to identify the genetic defect in a family with idiopathic ventricular fibrillation (IVF) manifesting in childhood and adolescence. BACKGROUND: Although sudden cardiac death in the young is rare, it frequently presents as the first clinical manifestation of an underlying inherited arrhythmia syndrome. Gene discovery for IVF is important as it enables the identification of individuals at risk, because except for arrhythmia, IVF does not manifest with identifiable clinical abnormalities. METHODS: Exome sequencing was carried out on 2 family members who were both successfully resuscitated from a cardiac arrest. RESULTS: We characterized a family presenting with a history of ventricular fibrillation (VF) and sudden death without electrocardiographic or echocardiographic abnormalities at rest. Two siblings died suddenly at the ages of 9 and 10 years, and another 2 were resuscitated from out-of-hospital cardiac arrest with documented VF at ages 10 and 16 years, respectively. Exome sequencing identified a missense mutation affecting a highly conserved residue (p.F90L) in the CALM1 gene encoding calmodulin. This mutation was also carried by 1 of the siblings who died suddenly, from whom DNA was available. The mutation was present in the mother and in another sibling, both asymptomatic but displaying a marginally prolonged QT interval during exercise. CONCLUSIONS: We identified a mutation in CALM1 underlying IVF manifesting in childhood and adolescence. The causality of the mutation is supported by previous studies demonstrating that F90 mediates the direct interaction of CaM with target peptides. Our approach highlights the utility of exome sequencing in uncovering the genetic defect even in families with a small number of affected individuals.

Health-related quality of life in long-term survivors of relapsed childhood acute lymphoblastic leukemia.

BACKGROUND: Relapses occur in about 20% of children with acute lymphoblastic leukemia (ALL). Approximately one-third of these children can be cured. Their risk for late effects is high because of intensified treatment, but their health-related quality of life (HRQOL) was largely unmeasured. Our aim was to compare HRQOL of ALL survivors with the general population, and of relapsed with non-relapsed ALL survivors. METHODOLOGY/PRINCIPAL FINDINGS: As part of the Swiss Childhood Cancer Survivor Study (SCCSS) we sent a questionnaire to all ALL survivors in Switzerland who had been diagnosed between 1976-2003 at age <16 years, survived ≥5 years, and were currently aged ≥16 years. HRQOL was assessed with the Short Form-36 (SF-36), which measures four aspects of physical health and four aspects of mental health. A score of 50 corresponded to the mean of a healthy reference population. We analyzed data from 457 ALL survivors (response: 79%). Sixty-one survivors had suffered a relapse. Compared to the general population, ALL survivors reported similar or higher HRQOL scores on all scales. Survivors with a relapse scored lower in general health perceptions (51.6) compared to those without (55.8;p=0.005), but after adjusting for self-reported late effects, this difference disappeared. CONCLUSION/SIGNIFICANCE: Compared to population norms, ALL survivors reported good HRQOL, even after a relapse. However, relapsed ALL survivors reported poorer general health than non-relapsed. Therefore, we encourage specialists to screen for poor general health in survivors after a relapse and, when appropriate, specifically seek and treat underlying late effects. This will help to improve patients' HRQOL.