Predictors of vitamin D status in New Zealand preschool children

Vitamin D deficiency has adverse health effects in young children. Our aims were to determine predictors of vitamin D status and then to use these factors to develop a practical tool to predict low 25(OH)D concentrations in preschool New Zealand children. A cross‐sectional sample of 1329 children aged 2 to <5 years were enrolled from throughout New Zealand in late‐winter to spring 2012. 25‐Hydroxyvitamin D (25(OH)D) was measured on dried blood spot (DBS) samples collected using finger‐prick sampling. Caregivers completed a questionnaire. Mean (SD) DBS 25(OH)D concentration was 52(19)nmol/L. 25(OH)D < 25 nmol/L was present in 86(7%), 25(OH)D < 50 nmol/L in 642(48%), 25(OH)D 50‐ < 75 nmol/L in 541(41%) and 25(OH)D > 75 nmol/L in 146(11%) of children. Factors independently associated with the risk of 25(OH)D < 25 nmol/L were female gender (OR 1.92,95%CI 1.17–3.14), other non‐European ethnicities (not including Māori or Pacific) (3.51,1.89–6.50), had olive‐dark skin colour (4.52,2.22–9.16), did not take vitamin D supplements (2.56,1.06–6.18), had mothers with less than secondary‐school qualifications (5.00,2.44–10.21) and lived in more deprived households (1.27,1.06–1.53). Children who drank toddler milk (vitamin D fortified cow's milk formula marketed to young children) had a zero risk of 25(OH)D < 25 nmol/L. The predictive tool identified children at risk of 25(OH)D < 25 nmol/L with sensitivity 42%, specificity 97% and ROC area‐under‐curve 0.76(95%CI 0.67–0.86, p < 0.001). Predictors of low vitamin D status were consistent with those identified in previous studies of New Zealand children. The tool had insufficient predictive ability for use in clinical situations, and suggests a need to promote safe, inexpensive testing to determine vitamin D status in preschool children.     

Dietary Patterns,Their Nutrients,and Associations with Socio-Demographic and Lifestyle Factors in Older New Zealand Adults

Dietary patterns analyse combinations of foods eaten. This cross-sectional study identified dietary patterns and their nutrients. Associations between dietary patterns and socio-demographic and lifestyle factors were examined in older New Zealand adults. Dietary data (109-item food frequency questionnaire) from the Researching Eating, Activity and Cognitive Health (REACH) study (n = 367, 36% male, mean age = 70 years) were collapsed into 57 food groups. Using principal component analysis, three dietary patterns explained 18% of the variation in diet. Dietary pattern associations with sex, age, employment, living situation, education, deprivation score, physical activity, alcohol, and smoking, along with energy-adjusted nutrient intakes, were investigated using regression analysis. Higher ‘Mediterranean’ dietary pattern scores were associated with being female, higher physical activity, and higher education (p < 0.001, R² = 0.07). Higher ‘Western’ pattern scores were associated with being male, higher alcohol intake, living with others, and secondary education (p < 0.001, R² = 0.16). Higher ‘prudent’ pattern scores were associated with higher physical activity and lower alcohol intake (p < 0.001, R² = 0.15). There were positive associations between beta-carotene equivalents, vitamin E, and folate and ‘Mediterranean’ dietary pattern scores (p < 0.0001, R² ≥ 0.26); energy intake and ‘Western’ scores (p < 0.0001, R² = 0.43); and fibre and carbohydrate and ‘prudent’ scores (p < 0.0001, R² ≥ 0.25). Socio-demographic and lifestyle factors were associated with dietary patterns. Understanding relationships between these characteristics and dietary patterns can assist in health promotion.     

In support of an early polypharmacy approach to the treatment of type 2 diabetes

Type 2 diabetes (T2DM) is a multifaceted disease, characterized by hyperglycaemia, resulting from a combination of insulin resistance, impaired incretin action and β-cell dysfunction leading to relative insulin deficiency. Although traditional anti-diabetes agents improve hyperglycaemia, they do so at a cost, which may entail hypoglycemia and increased body weight; exacerbating dyslipidemia, hypertension and components of insulin resistance and metabolic syndrome associated with T2DM-potentially increasing cardiovascular risk. At diagnosis, many patients with T2DM are treated with medical nutritional therapy (MNT) and exercise, then single or multiple oral anti-diabetes agents until treatment failure, when insulin is used. This strategy has been challenged by recommendations for polypharmacy approaches to the treatment of T2DM, as current strategies are unable to improve multiple aspects of the disease, nor are they likely to address underlying pathophysiology. Although the 2009 American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) treatment algorithm recommends a stepwise approach with MNT and metformin, later adding oral agents, incretin-based therapies or insulin, some experts have recommended a more aggressive approach. In his 2008 ADA Banting Lecture, Dr. Ralph DeFronzo recommended early treatment with metformin, TZD and exenatide at initiation of therapy. The authors' of this article recommend an aggressive early polypharmacy approach addressing underlying pathophysiology, including the incretin defect-with MNT and exercise, metformin and an incretin-based therapy and/or basal insulin if glycemic goal is not achieved within 3 months. This approach attempts to modify the disease, aiming for tight glycemic control, weight loss, reduced hypoglycemia, improvements to hypertension, dyslipidemia and insulin resistance-and improved cardiovascular outcomes.     

Long-term effects of exenatide therapy over 82 weeks on glycaemic control and weight in over-weight metformin-treated patients with type 2 diabetes mellitus

AIM: The ability of the incretin mimetic exenatide to improve glycaemic control and reduce body weight was assessed over 82 weeks in patients with type 2 diabetes failing to achieve glycaemic control with maximally effective doses of metformin. METHODS: In this interim 82-week analysis, 150 (total cohort) of an eligible population of 183 patients opted to continue exenatide treatment in an uncontrolled open-label extension of a 30-week double-blind, placebo-controlled trial. Of these, 92 patients (completer cohort) achieved 82 weeks of exenatide therapy. Patients continued metformin throughout the study. RESULTS: At the end of the placebo-controlled trial, exenatide resulted in an haemoglobin A1c (HbA1c) reduction from baseline of -1.0 +/- 0.1% (mean +/- SE) (exenatide treatment arms), with durable HbA1c reductions after 82 weeks of -1.3 +/- 0.1%. The percent of patients who achieved HbA1c < or = 7% at weeks 30 and 82 was 46 and 59% respectively. After 30 weeks, exenatide caused a reduction in weight from baseline of -3.0 +/- 0.6 kg, with a progressive reduction in weight of -5.3 +/- 0.8 kg after 82 weeks. In addition, exenatide treatment produced clinically significant improvements in cardiovascular risk factors after 82 weeks. The most frequent adverse event after 30 and 82 weeks of exenatide was nausea, which was generally of mild-or-moderate intensity. It decreased in incidence after initiation in the controlled trial and the uncontrolled open-label extension. Hypoglycaemia was rare, with no severe events. CONCLUSION: Exenatide was generally well tolerated, producing a durable reduction in HbA1c and a progressive reduction in weight over 82 weeks in patients with type 2 diabetes failing to achieve glycaemic control with metformin.     

The Subcellular Localisation of the Human Papillomavirus (HPV) 16 E7 Protein in Cervical Cancer Cells and Its Perturbation by RNA Aptamers

Human papillomavirus (HPV) is the most common viral infection of the reproductive tract, affecting both men and women. High-risk oncogenic types are responsible for almost 90% of anogenital and oropharyngeal cancers including cervical cancer. Some of the HPV “early” genes, particularly E6 and E7, are known to act as oncogenes that promote tumour growth and malignant transformation. Most notably, HPV-16 E7 interacts with the tumour suppressor protein pRb, promoting its degradation, leading to cell cycle dysregulation in infected cells. We have previously shown that an RNA aptamer (termed A2) selectively binds to HPV16 E7 and is able to induce apoptosis in HPV16-transformed cervical carcinoma cell lines (SiHa) through reduction of E7 levels. In this study, we investigated the effects of the A2 aptamer on E7 localisation in order to define its effects on E7 activity. We demonstrate for the first time that E7 localised to the plasma membrane. In addition, we show that A2 enhanced E7 localisation in the ER and that the A2-mediated reduction of E7 was not associated with proteasomal degradation. These data suggest that A2 perturbs normal E7 trafficking through promoting E7 ER retention.     

Clustering of haemostatic variables and the effect of high cashew and walnut diets on these variables in metabolic syndrome patients.

We investigated the effect of a high walnut and cashew diet on haemostatic variables in people with the metabolic syndrome. Factor analysis was used to determine how the haemostatic variables cluster with other components of the metabolic syndrome and multiple regression to determine possible predictors. This randomized, control, parallel, controlled-feeding trial included 68 subjects who complied with the Third National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol criteria. After a 3-week run-in following the control diet, subjects were divided into three groups receiving either walnuts or cashews (20 energy%) or a control diet for 8 weeks. The nut intervention had no significant effect on von Willebrand factor antigen, fibrinogen, factor VII coagulant activity, plasminogen activator inhibitor 1 activity, tissue plasminogen activator activity or thrombin activatable fibrinolysis inhibitor. Statistically, fibrinogen clustered with the body-mass-correlates and acute phase response factors, and factor VII coagulant activity clustered with high-density lipoprotein cholesterol (HDL-C). Tissue plasminogen activator activity, plasminogen activator inhibitor 1 activity and von Willebrand factor antigen clustered into a separate endothelial function factor. HDL-C and markers of obesity were the strongest predictors of the haemostatic variables. We conclude that high walnut and cashew diets did not influence haemostatic factors in this group of metabolic syndrome subjects. The HDL-C increase and weight loss may be the main focus of dietary intervention for the metabolic syndrome. Furthermore, diet composition may have only limited effects if weight loss is not achieved.     

Excisional arthroplasty for patellar loosening in total knee arthroplasty

Four thousand two hundred eighty-seven cases of Anatomic Graduated Components total knee replacements with a cemented, single-peg, all-polyethylene patellar component were performed at our institution over the past 15 years. One hundred eighty cases of patellar component loosening were found. Eleven knees (0.3%) in 11 patients required isolated patellar component reoperation. In all cases, the patellar component was excised and not reimplanted. The average follow-up for the 11 patients was 2.2 years. Five had a complete minimum follow-up of 2 years following reoperation. Pain and function were improved. Complications included infection in 3 knees and extensor lag in 1 knee. Because of the complication rate associated with isolated patellar component excision caused by a loose patellar component, we recommend surgical removal of the patellar component only in cases of severe pain and/or prominence of the component.