A telephone intervention to achieve differentiation in dietary intake: a randomized trial in paediatric primary care.

BACKGROUND: Telehealth offers opportunities to extend clinical and research interventions for paediatric obesity. OBJECTIVES: To assess utility of a telephone intervention, implemented through a national primary care paediatric research network, for promoting differentiation in dietary intake, consistent with either a low-glycemic load (Low GL) or Low Fat prescription, among overweight/obese school-age children. METHODS: Five-week telephone dietary counselling intervention for parents of overweight/obese school-age children recruited through the Slone Center Office-based Research Network. Parent-child dyads were randomized to Low GL or Low Fat diet. Primary outcomes were dietary GL and dietary fat, adjusted for energy intake and assessed by 24-h dietary recall. RESULTS: Subjects were randomized to Low GL (n = 11, 8.1 ± 1.7 years, 45.5% male) or Low Fat (n = 11, 8.2 ± 2.0 years, 36.4% male), with no baseline differences. Overall, 86% of subjects attended at least four of five counselling sessions, and study completion rate was 91% (based on completion of the final dietary recalls). Reported satisfaction was high. In adjusted analyses limited to 'recall completers,' reduction in dietary GL (g/1000 kcal) achieved within the Low GL group was significant (p = 0.01) and greater than the change in dietary GL in the Low Fat group (mean ± SE; -12.9 ± 4.4 vs. 5.1 ± 4.9, p = 0.03). Similarly, reduction in dietary fat (% of total energy) within the Low Fat group was significant (-5.6 ± 2.5, p = 0.046) but with no difference between groups (p = 0.25). CONCLUSION: A telephone-based dietary intervention for overweight/obese children, implemented through a national paediatric research network, fostered prescribed dietary changes. ClinicalTrials.gov registration: NCT00620152.

Outcomes from an orientation model to reduce attrition in paediatric weight management.

We aimed to reduce attrition of newly referred patients in a paediatric weight management programme by implementing an orientation to address families' expectations and screen for and support behavioural and mental health problems and psychosocial stressors at programme outset. Orientation impact was monitored with run charts with percentages of scheduled encounters completed. Long-term impact was assessed by comparing patients in the initial 6 months of the orientation to a baseline group of referred patients during the same 6-month time interval in the prior year (Pre-Orientation Group). The outcome measure was programme attrition within 15 months. Groups were compared using Kaplan-Meier survival analysis and Cox proportional hazards regression modelling. Patients in the Orientation Group had a 23% increased odds of attrition compared to patients in the Pre-Orientation group (adjusted Hazard ratio, aHR 1.23; 95% confidence interval, CI: 1.01, 1.51) and shorter median duration of follow-up (2.0 vs. 2.9 months, P = 0.004). An increase in body mass index z-score of 1 unit resulted in a nearly fivefold increased odds of attrition (aHR 5.24; 95% CI: 2.95, 9.3). An orientation for new patients did not reduce attrition within 15 months. We suggest that ongoing retention strategies should be embedded into the treatment phase of the programme.

Estimated morbidity and mortality in adolescents and young adults diagnosed with Type 2 diabetes mellitus.

AIMS: To estimate remaining life expectancy (RLE), quality-adjusted life expectancy (QALE), causes of death and lifetime cumulative incidence of microvascular/macrovascular complications of diabetes for youths diagnosed with Type 2 diabetes. METHODS: A Markov-like computer model simulated the life course for a hypothetical cohort of adolescents/young adults in the USA, aged 15-24 years, newly diagnosed with Type 2 diabetes following either conventional or intensive treatment based on the UK Prospective Diabetes Study. Outcomes included RLE, discounted QALE in quality-adjusted life years (QALYs), cumulative incidence of microvascular/macrovascular complications and causes of death. RESULTS: Compared with a mean RLE of 58.6 years for a 20-year-old in the USA without diabetes, conventional treatment produced an average RLE of 43.09 years and 22.44 discounted QALYs. Intensive treatment afforded an incremental 0.98 years and 0.44 discounted QALYs. Intensive treatment led to lower lifetime cumulative incidence of all microvascular complications and lower mortality from microvascular complications (e.g. end-stage renal disease (ESRD) death 19.4% vs. 25.2%). Approximately 5% with both treatments had ESRD within 25 years. Lifetime cumulative incidence of coronary heart disease (CHD) increased with longer RLE and greater severity of CHD risk factors. Incorporating disutility (loss in health-related quality of life) of intensive treatment resulted in net loss of QALYs. CONCLUSIONS: Adolescents/young adults with Type 2 diabetes lose approximately 15 years from average RLE and may experience severe, chronic complications of Type 2 diabetes by their 40s. The net clinical benefit of intensive treatment may be sensitive to preferences for treatment. A comprehensive management plan that includes early and aggressive control of cardiovascular risk factors is likely needed to reduce lifetime risk of CHD.

Expression of eukaryotic proteins in soluble form in Escherichia coli.

At the optimum temperature for its growth (37 degrees C), Escherichia coli tends to accumulate heterologous proteins in insoluble form. Fusion protein technology has been used to increase the solubility of overexpressed proteins in this organism, but with variable degrees of success. Fusion to a mutant form of DsbA (DsbAmut) confers higher levels of solubility to heterologous proteins in a reproducible way, even when E. coli is grown at 37 degrees C. We have shown this to be true with a diverse sample of eukaryotic proteins: IGF-I, IGFBP-3, 3C proteinase, TGF beta-2, sTGF beta-RII, BDNF, GDNF, mEGFBP, leptin, and GFP. In addition, we have investigated the effects of charge average and proline content on the solubility of DsbAmut fusions. Coexpression of a protein prolyl isomerase [cyclophilin (L-)] and modification of selected asparagine residues to aspartic acid appear to have beneficial effects on the accumulation of soluble heterologous proteins.