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Background: Despite the association with more advanced nodal stage, patients with human papillomavirus (HPV) positive oropharyngeal cancers have better outcomes. We examined whether the HPV can modify the effect of known prognostic factors in tonsillar cancer., Patients and Methods: A total of 489 patients from 10 centres were followed up for recurrence or death for a median of 3.2 years. Determinants of the rate of locoregional recurrence, death from tonsillar cancer and overall survival were modelled using Cox regression., Results: The prognostic value of T and N stages were modified by HPV as indicated by statistically significant interaction terms. After adjusting for age, gender and treatment, T stage appeared relevant only for HPV-positive cancers (where a higher T stage was associated with worse outcomes). There was some evidence that N stage was a more relevant prognostic factor for HPV-negative than -positive cancers. There was no evidence that the HPV modifies the effect of age, gender or grade on outcomes., Conclusions: This study suggests that the prognostic significance of the conventional staging system in tonsillar cancer is modified by HPV.

Background: Despite bronchiectasis being increasingly recognised as an important cause of chronic respiratory morbidity in both indigenous and non-indigenous settings globally, high quality evidence to inform management is scarce. It is assumed that antibiotics are efficacious for all bronchiectasis exacerbations, but not all practitioners agree. Inadequately treated exacerbations may risk lung function deterioration. Our study tests the hypothesis that both oral azithromycin and amoxicillin-clavulanic acid are superior to placebo at improving resolution rates of respiratory exacerbations by day 14 in children with bronchiectasis unrelated to cystic fibrosis., Methods: We are conducting a bronchiectasis exacerbation study (BEST), which is a multicentre, randomised, double-blind, double-dummy, placebo-controlled, parallel group trial, in five centres (Brisbane, Perth, Darwin, Melbourne, Auckland). In the component of BEST presented here, 189 children fulfilling inclusion criteria are randomised (allocation-concealed) to receive amoxicillin-clavulanic acid (22.5 mg/kg twice daily) with placebo-azithromycin; azithromycin (5 mg/kg daily) with placebo-amoxicillin-clavulanic acid; or placebo-azithromycin with placebo-amoxicillin-clavulanic acid for 14 days. Clinical data and a paediatric cough-specific quality of life score are obtained at baseline, at the start and resolution of exacerbations, and at day 14. In most children, blood and deep nasal swabs are also collected at the same time points. The primary outcome is the proportion of children whose exacerbations have resolved at day 14. The main secondary outcome is the paediatric cough-specific quality of life score. Other outcomes are time to next exacerbation; requirement for hospitalisation; duration of exacerbation; and spirometry data. Descriptive viral and bacteriological data from nasal samples and blood markers will also be reported., Discussion: Effective, evidence-based management of exacerbations in people with bronchiectasis is clinically important. Yet, there are few randomised controlled trials (RCTs) in the neglected area of non-cystic fibrosis bronchiectasis. Indeed, no published RCTs addressing the treatment of bronchiectasis exacerbations in children exist. Our multicentre, double-blind RCT is designed to determine if azithromycin and amoxicillin-clavulanic acid, compared with placebo, improve symptom resolution on day 14 in children with acute respiratory exacerbations. Our planned assessment of the predictors of antibiotic response, the role of antibiotic-resistant respiratory pathogens, and whether early treatment with antibiotics affects duration and time to the next exacerbation, are also all novel., Trial Registration: Australia and New Zealand Clinical Trials Register (ANZCTR) number ACTRN12612000011886.

Abdominal fat, and in particular, visceral adipose tissue (VAT), is the critical fat depot associated with metabolic aberrations. At present, VAT can only be accurately measured by computed tomography or magnetic resonance imaging (MRI). This study was designed to compare a new abdominal bioelectrical impedance (BIA) device against total abdominal adipose tissue (TAAT) and VAT area measurements made from an abdominal MRI scan, and to assess its reliability and accuracy. One-hundred twenty participants were recruited, stratified by gender and BMI. Participants had triplicate measures of abdominal fat and waist circumference (WC) with the AB-140 (Tanita, Tokyo, Japan) and WC measurements using a manual tape measure. A single abdominal MRI scan was performed as the reference method. Triplicate measures with the AB-140 showed excellent precision for "visceral fat level," trunk fat %, and WC. AB-140 "visceral fat level" showed significantly stronger correlations with MRI TAAT area than with MRI VAT area (r = 0.94 vs. 0.65 in men and 0.92 vs. 0.64 in women). AB-140 WC showed good correlation with manual WC measurements (r = 0.95 in men and 0.90 in women). AB-140 and manual WCs showed comparable correlations with MRI TAAT area (r = 0.92 and 0.96 in men and 0.88 and 0.88 in women). AB-140 is a simple, quick, and precise technique to measure abdominal fat and WC in healthy adults. It provides a useful proxy for TAAT measured by MRI, comparable to the correlation obtained with manual WC measurements. Neither the AB-140 abdominal fat measures nor WC measurement appear to provide a useful proxy measure of VAT.

Background: Insulin sensitivity (Si) is improved by weight loss and exercise, but the effects of the replacement of saturated fatty acids (SFAs) with monounsaturated fatty acids (MUFAs) or carbohydrates of high glycemic index (HGI) or low glycemic index (LGI) are uncertain., Objective: We conducted a dietary intervention trial to study these effects in participants at risk of developing metabolic syndrome., Design: We conducted a 5-center, parallel design, randomized controlled trial [RISCK (Reading, Imperial, Surrey, Cambridge, and Kings)]. The primary and secondary outcomes were changes in Si (measured by using an intravenous glucose tolerance test) and cardiovascular risk factors. Measurements were made after 4 wk of a high-SFA and HGI (HS/HGI) diet and after a 24-wk intervention with HS/HGI (reference), high-MUFA and HGI (HM/HGI), HM and LGI (HM/LGI), low-fat and HGI (LF/HGI), and LF and LGI (LF/LGI) diets., Results: We analyzed data for 548 of 720 participants who were randomly assigned to treatment. The median Si was 2.7 × 10(-4) mL · μU(-1) · min(-1) (interquartile range: 2.0, 4.2 × 10(-4) mL · μU(-1) · min(-1)), and unadjusted mean percentage changes (95% CIs) after 24 wk treatment (P = 0.13) were as follows: for the HS/HGI group, -4% (-12.7%, 5.3%); for the HM/HGI group, 2.1% (-5.8%, 10.7%); for the HM/LGI group, -3.5% (-10.6%, 4.3%); for the LF/HGI group, -8.6% (-15.4%, -1.1%); and for the LF/LGI group, 9.9% (2.4%, 18.0%). Total cholesterol (TC), LDL cholesterol, and apolipoprotein B concentrations decreased with SFA reduction. Decreases in TC and LDL-cholesterol concentrations were greater with LGI. Fat reduction lowered HDL cholesterol and apolipoprotein A1 and B concentrations., Conclusions: This study did not support the hypothesis that isoenergetic replacement of SFAs with MUFAs or carbohydrates has a favorable effect on Si. Lowering GI enhanced reductions in TC and LDL-cholesterol concentrations in subjects, with tentative evidence of improvements in Si in the LF-treatment group. This trial was registered at clinicaltrials.gov as ISRCTN29111298.

Our objective in this study was to develop and implement an effective intervention strategy to manipulate the amount and composition of dietary fat and carbohydrate (CHO) in free-living individuals in the RISCK study. The study was a randomized, controlled dietary intervention study that was conducted in 720 participants identified as higher risk for or with metabolic syndrome. All followed a 4-wk run-in reference diet [high saturated fatty acids (SF)/high glycemic index (GI)]. Volunteers were randomized to continue this diet for a further 24 wk or to 1 of 4 isoenergetic prescriptions [high monounsaturated fatty acids (MUFA)/high GI; high MUFA/low GI; low fat (LF)/high GI; and LF/low GI]. We developed a food exchange model to implement each diet. Dietary records and plasma phospholipid fatty acids were used to assess the effectiveness of the intervention strategy. Reported fat intake from the LF diets was significantly reduced to 28% of energy (%E) compared with 38%E from the HM and LF diets. SF intake was successfully decreased in the HM and LF diets to < or =10%E compared with 17%E in the reference diet (P = 0.001). Dietary MUFA in the HM diets was approximately 17%E, significantly higher than in the reference (12%E) and LF diets (10%E) (P = 0.001). Changes in plasma phospholipid fatty acids provided further evidence for the successful manipulation of fat intake. The GI of the HGI and LGI arms differed by approximately 9 points (P = 0.001). The food exchange model provided an effective dietary strategy for the design and implementation across multiple sites of 5 experimental diets with specific targets for the proportion of fat and CHO.

Background: This study aimed to determine if people living in communities with higher socio-economic deprivation are at an increased risk of cognitive and functional impairment even after controlling for the effects of individual socio-economic status., Methods: We analysed cross-sectional data from the Medical Research Council Cognitive Function and Ageing Study which consists of a community-based sample of Cambridgeshire, Gwynedd, Newcastle, Nottingham and Oxford. The study included 13 004 men and women aged 65 years and over who were randomly selected from Family Health Services Authority computerized records after being stratified to ensure equal numbers of those aged 75 years and over and those under 75 years. The outcome measures were cognitive impairment (Mini-Mental State Exam 0-21) and functional impairment (Instrumental Activities of Daily Living and/or Activities of Daily Living disability)., Results: Individuals living in more deprived areas, as measured by the Townsend deprivation score, were found to have a higher prevalence of cognitive impairment [odds ratio (OR) (most deprived versus least deprived quintile) = 2.3; 95% confidence interval (CI)1.8-3.0; P < 0.001] and functional impairment [OR (most deprived versus least) = 1.6; 95% CI 1.4-1.9; P < 0.001] after controlling for age, sex, centre effects, education and social class., Conclusions: There is a significantly higher prevalence of cognitive impairment and functional impairment in elderly individuals living in socio-economically deprived areas regardless of their own socio-economic status. This evidence is of relevance for informing public health policy and those allocating resources for the long-term care of the elderly.

Objectives: Longitudinal studies of the elderly are complicated by the loss of individuals between waves due to death or other dropout mechanisms. Factors that affect dropout may well be similar from one study to another. This article systematically reviews all large population-based studies of the elderly (published 1966-2002) that report on differences in individual characteristics between people who remain and people who dropout at follow-up., Study Design and Setting: A systematic review of articles that investigate attrition after baseline interview., Results: Twelve studies were found that investigated dropout other than death using unadjusted, multivariable methods or both. The unadjusted analyses showed many significant factors related to attrition. Multivariable analyses showed two main independent factors were related to increased attrition: increasing age and cognitive impairment. People who were very ill or frail had higher dropout rates, and people in worse health were less likely to be recontactable., Conclusions: Multivariable methods of analyzing attrition in longitudinal studies show consistent patterns of dropout between differing studies, with a small number of key relationships. These findings will assist researchers when planning studies of older people, and provide insight into the possible biases in longitudinal studies introduced by differential dropout.