A practical evidence-based approach to management of type 2 diabetes in children and young people (CYP): UK consensus.

BACKGROUND: Type 2 diabetes in young people is an aggressive disease with a greater risk of complications leading to increased morbidity and mortality during the most productive years of life. Prevalence in the UK and globally is rising yet experience in managing this condition is limited. There are no consensus guidelines in the UK for the assessment and management of paediatric type 2 diabetes. METHODS: Multidisciplinary professionals from The Association of Children's Diabetes Clinicians (ACDC) and the National Type 2 Diabetes Working Group reviewed the evidence base and made recommendations using the Grading Of Recommendations, Assessment, Development and Evaluation (GRADE) methodology. RESULTS AND DISCUSSION: Young people with type 2 diabetes should be managed within a paediatric diabetes team with close working with adult diabetes specialists, primary care and other paediatric specialties. Diagnosis of diabetes type can be challenging with many overlapping features. Diabetes antibodies may be needed to aid diagnosis. Co-morbidities and complications are frequently present at diagnosis and should be managed holistically. Lifestyle change and metformin are the mainstay of early treatment, with some needing additional basal insulin. GLP1 agonists should be used as second-line agents once early ketosis and symptoms are controlled. Glycaemic control improves microvascular but not cardiovascular risk. Reduction in excess adiposity, smoking prevention, increased physical activity and reduction of hypertension and dyslipidaemia are essential to reduce major adverse cardiovascular events. CONCLUSIONS: This evidence-based guideline aims to provide a practical approach in managing this condition in the UK.

Applying generalizability theory to examine assessments of subjective cognitive complaints: whose reports should we rely on - participant versus informant?

OBJECTIVES: This study aimed to apply the generalizability theory (G-theory) to investigate dynamic and enduring patterns of subjective cognitive complaints (SCC), and reliability of two widely used SCC assessment tools. DESIGN: G-theory was applied to assessment scales using longitudinal measurement design with five assessments spanning 10 years of follow-up. SETTING: Community-dwelling older adults aged 70-90 years and their informants, living in Sydney, Australia, participated in the longitudinal Sydney Memory and Ageing Study. PARTICIPANTS: The sample included 232 participants aged 70 years and older, and 232 associated informants. Participants were predominantly White Europeans (97.8%). The sample of informants included 76 males (32.8%), 153 females (65.9%), and their age ranged from 27 to 86 years, with a mean age of 61.3 years (SD = 14.38). MEASUREMENTS: The Memory Complaint Questionnaire (MAC-Q) and the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). RESULTS: The IQCODE demonstrated strong reliability in measuring enduring patterns of SCC with G = 0.86. Marginally acceptable reliability of the 6-item MAC-Q (G = 0.77-0.80) was optimized by removing one item resulting in G = 0.80-0.81. Most items of both assessments were measuring enduring SCC with exception of one dynamic MAC-Q item. The IQCODE significantly predicted global cognition scores and risk of dementia incident across all occasions, while MAC-Q scores were only significant predictors on some occasions. CONCLUSIONS: While both informants' (IQCODE) and self-reported (MAC-Q) SCC scores were generalizable across sample population and occasions, self-reported (MAC-Q) scores may be less accurate in predicting cognitive ability and diagnosis of each individual.

Phase 2 multicentre study of single-agent ofatumumab in previously untreated follicular lymphoma: CALGB 50901 (Alliance).

Rituximab monotherapy has proven efficacy in treatment-naïve, asymptomatic advanced-stage follicular lymphoma (FL). Ofatumumab is a fully humanized anti-CD20 monoclonal antibody with increased CD20 affinity and complement-dependent cytotoxicity. This phase 2 trial (NCT01190449) evaluated ofatumumab in patients with untreated, low/intermediate-risk FL International Prognostic Index (FLIPI), advanced-stage FL to determine single-agent efficacy. Patients with measurable disease in stages III/IV or bulky stage II, regardless of Groupe d'Etude des Lymphomes Folliculaires criteria, received 4 weekly 1000 mg doses followed by four extended induction doses once every 8 weeks. Primary endpoint was overall response rate (ORR) to 1000 mg; secondary endpoints were progression-free survival (PFS) and safety. Fifty-one patients were enrolled. Fifteen patients were randomized to 500 mg prior to discontinuing that arm for slow accrual. Among 36 patients on the 1000 mg arm, ORR was 84%, median PFS was 1·9 years and median response duration was 23·7 months. All patients remain alive. No grade 4 infusion reactions or grade 3/4 infections occurred. Grade 3 infusion reactions occurred in 25% in the 1000 mg arm only (all first infusion); all but two patients continued on study. Discontinuation was 6% for the total study population. Ofatumumab monotherapy administered by extended induction in untreated, low/intermediate-risk FLIPI, advanced-stage FL is well tolerated and active. Activity appears similar to that reported with single-agent rituximab.

The Vascular Behavioral and Cognitive Disorders criteria for vascular cognitive disorders: a validation study.

BACKGROUND AND PURPOSE: The Vascular Behavioral and Cognitive Disorders (VASCOG) criteria for vascular cognitive disorders were published in 2014, but their concurrent and predictive validity have not been examined. METHODS: Participants (N = 165, aged 49-86 years) were from Sydney Stroke Study, a longitudinal study of post-stroke cognitive impairment and dementia. Diagnoses using the National Institute of Neurological Disorders and Stroke - Association Internationale pour la Recherché et l'Enseignement en Neurosciences (NINDS-AIREN), the Alzheimer's Disease Diagnostic and Treatment Centers (ADDTC) and the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV), criteria for vascular dementia (VaD) were made by consensus at multidisciplinary case conferences. Diagnoses for mild vascular cognitive disorder (mVCD) and VaD using VASCOG, DSM-5 and the Vascular Impairment of Cognition Classification Consensus Study (VICCCS) criteria were made by two study authors. Agreement levels between criteria sets were examined using Cohen's kappa (κ). The ability of VaD diagnoses to predict mortality over 10 years and of mVCD to predict dementia over 5 years was investigated. RESULTS: The VASCOG criteria yielded rates of mVCD slightly lower than for DSM-5 and VICCCS. VaD rates were similar for all criteria, although slightly lower for DSM-IV. Agreement between the VASCOG, VICCCS and DSM-5 criteria was excellent for VaD and mVCD (κ = 0.83-1.0), but lower for VaD between VASCOG and the other criteria (κ = 0.47-0.63). VaD-based mortality predictions were similar for the VASCOG, VICCCS and DSM-5 criteria, and higher than those for other criteria. The prediction of incident dementia within 5 years from mVCD was slightly lower with VASCOG criteria than with DSM-5 and VICCCS criteria. CONCLUSIONS: The VASCOG criteria have greater sensitivity, modest concurrent validity and better predictive validity than older criteria for VaD, but are comparable to DSM-5 and VICCCS criteria. Their operationalization and inclusion of a mild VCD category make them useful for clinical and research applications.

The impact of type 2 diabetes and body mass index on cerebral structure is modulated by brain reserve.

BACKGROUND AND PURPOSE: Body mass index (BMI), hyperglycaemia and type 2 diabetes and their interactive effects are associated with brain volume atrophy in ageing. It remains to be established if these risk factors are particularly concerning in individuals with high or low brain volumes. METHODS: Demographics, venous blood and magnetic resonance imaging data were collected for 494 healthy community-living adults aged 53-78 (mean 65) years, as part of the Personality and Total Health Through Life study. Associations between BMI, blood glucose, diabetes status and brain volume (whole brain, grey matter, white matter and subcortical structures) were investigated using quantile regression. RESULTS: Quantile regression revealed vulnerability to BMI × glucose interactions particularly in lower volumes and significant main effects for type 2 diabetes particularly in higher volumes. Diabetes was most strongly associated with brain volumes. The association between BMI, blood glucose and diabetes was not consistent across the full range of brain volumes. CONCLUSION: Explicit investigation of the upper and lower boundaries of brain volume distributions was valuable. We found evidence of protective reserve from higher brain volumes and that a combination of high BMI and higher blood glucose was particularly concerning for individuals with lower brain volumes.

Body mass index is associated with cortical thinning with different patterns in mid- and late-life.

OBJECTIVE: High BMI at midlife is associated with increased risk of dementia as well as faster decline in cognitive function. In late-life, however, high BMI has been found to be associated with both increased and decreased dementia risk. The objective of this study was to investigate the neural substrates of this age-related change in body mass index (BMI) risk. METHODS: We measured longitudinal cortical thinning over the whole brain, based on magnetic resonance imaging scans for 910 individuals aged 44-66 years at baseline. Subjects were sampled from a large population study (PATH, Personality and Total Health through Life). After attrition and exclusions, the final analysis was based on 792 individuals, including 387 individuals aged 60-66 years and 405 individuals aged 44-49 years. A mixed-effects model was used to test the association between cortical thinning and baseline BMI, as well as percentage change in BMI. RESULTS: Increasing BMI was associated with increased cortical thinning in posterior cingulate at midlife (0.014 mm kg-1 m-2, confidence interval; CI=0.005, 0.023, P<0.05 false discovery rate (FDR) corrected). In late-life, increasing BMI was associated with reduced cortical thickness, most prominently in the right supramarginal cortex (0.010 mm kg-1 m-2, CI=0.005-0.016, P<0.05 FDR corrected), as well as frontal regions. In late-life, decreasing BMI was also associated with increased cortical thinning, including right caudal middle frontal cortex (0.014 mm kg-1 m-2 (CI=0.006-0.023, P<0.05 FDR corrected). CONCLUSIONS: The pattern of cortical thinning-in association with increasing BMI at both midlife and late-life-is consistent with known obesity-related dementia risk. Increased cortical thinning in association with decreasing BMI at late-life may help explain the 'obesity paradox', where high BMI in midlife appears to be a risk factor for dementia, but high BMI in late-life appears, at times, to be protective.

Intragastric balloon as an adjunct to lifestyle programme in severely obese adolescents: impact on biomedical outcomes and skeletal health.

Intragastric Balloons are a temporary, reversible and safer option compared to bariatric surgery to promote significant weight loss, leading to improved metabolic outcomes. However, due to subsequent weight regain, alternative procedures are now preferred in adults. In adolescents, more amenable to lifestyle change, balloons may be an alternative to less reversible procedures. Our aim was to assess the tolerability and efficacy of the intragastric balloon in severely obese adolescents and the impact of associated weight loss on biomedical outcomes (glucose metabolism, blood pressure, lipid profiles) and bone density. A 2-year cohort study of 12 adolescents (BMI >3.5 s.d., Tanner stage >4) following 6 months intragastric balloon placement was carried out. Subjects underwent anthropometry, oral glucose tolerance test, and DEXA scans at 0, 6 and 24 months. The results showed clinically relevant improvements in blood pressure, insulin: glucose metabolism, liver function and sleep apnoea at 6 months. Changes were not sustained at 2 years though some parameters (Diastolic BP, HBA1c, insulin AUC) demonstrated longer-term improvement despite weight regain. Despite weight loss, bone mass accrual showed age appropriate increases. In conclusion, the intragastric balloon was safe, well tolerated and effective in supporting short-term weight loss and clinically relevant improvement in obesity-related complications, which resolved in some individuals. Benefits were not sustained in the majority at 2 years.

Genetic and Environmental Influences on Language Ability in Older Adults: Findings from the Older Australian Twins Study.

We used a sub-sample from the Older Australian Twins Study to estimate the heritability of performance on three tests of language ability: Boston Naming Test (BNT), Letter/Phonemic Fluency (FAS) and Category/Semantic Fluency (CFT) Tests. After adjusting for age, sex, education, mood, and global cognition (GC), heritability estimates obtained for the three tests were 0.35, 0.59, and 0.20, respectively. Multivariate analyses showed that the genetic correlation were high for BNT and CFT (0.61), but low for BNT and FAS (0.17), and for FAS and CFT (0.28). Genetic modelling with Cholesky decomposition indicated that the covariation between the three measures could be explained by a common genetic factor. Environmental correlations between the language ability measures were low, and there were considerable specific environmental influences for each measure. Future longitudinal studies with language performance and neuroimaging data can further our understanding of genetic and environmental factors involved in the process of cognitive aging.

Common and distinct patterns of grey-matter volume alteration in major depression and bipolar disorder: evidence from voxel-based meta-analysis.

Finding robust brain substrates of mood disorders is an important target for research. The degree to which major depression (MDD) and bipolar disorder (BD) are associated with common and/or distinct patterns of volumetric changes is nevertheless unclear. Furthermore, the extant literature is heterogeneous with respect to the nature of these changes. We report a meta-analysis of voxel-based morphometry (VBM) studies in MDD and BD. We identified studies published up to January 2015 that compared grey matter in MDD (50 data sets including 4101 individuals) and BD (36 data sets including 2407 individuals) using whole-brain VBM. We used statistical maps from the studies included where available and reported peak coordinates otherwise. Group comparisons and conjunction analyses identified regions in which the disorders showed common and distinct patterns of volumetric alteration. Both disorders were associated with lower grey-matter volume relative to healthy individuals in a number of areas. Conjunction analysis showed smaller volumes in both disorders in clusters in the dorsomedial and ventromedial prefrontal cortex, including the anterior cingulate cortex and bilateral insula. Group comparisons indicated that findings of smaller grey-matter volumes relative to controls in the right dorsolateral prefrontal cortex and left hippocampus, along with cerebellar, temporal and parietal regions were more substantial in major depression. These results suggest that MDD and BD are characterised by both common and distinct patterns of grey-matter volume changes. This combination of differences and similarities has the potential to inform the development of diagnostic biomarkers for these conditions.

Intra-gastric balloon as an adjunct to lifestyle support in severely obese adolescents; impact on weight, physical activity, cardiorespiratory fitness and psychosocial well-being.

BACKGROUND: Severe adolescent obesity (body mass index (BMI) >99.6th centile) is a significant public health challenge. Current non-invasive treatments, including community-based lifestyle interventions, are often of limited effectiveness in this population, with NICE guidelines suggesting the use of bariatric surgery as the last line of treatment. Health professionals are understandably reluctant to commission bariatric surgery and as an alternative, the use of an intra-gastric balloon as an adjunct to a lifestyle programme might offer a reversible, potentially safer and less invasive option. OBJECTIVES: Explore the use of an intra-gastric balloon as an adjunct to a lifestyle support programme, to promote weight loss in severely obese adolescents. Outcomes included weight loss, waist and hip measurements, psychosocial outcomes including health-related quality of life (HRQoL) and physical self perceptions, physical activity and cardiorespiratory fitness. METHOD: Non-randomised pilot study. RESULTS: Twelve severely obese adolescents (5 males, 7 females; mean age 15 years; BMI >3.5 s.d.; puberty stage 4 or more) and their families were recruited. Mean weight loss at 12 months (n=9) was 3.05 kg±14.69; d=0.002, P=0.550, and a BMI Z-score (n=12) change of 0.2 s.d.; d=0.7, P=0.002 was observed at 6 months with a large effect, but was not sustained at 12 months (mean change 0.1 s.d.; d=0.3, P=0.146). At 24 months (n=10), there was a weight gain from baseline of +9.9 kg±1.21 (d=0.4; P=0.433). Adolescent and parent HRQoL scores exceeded the minimal clinical important difference between baseline and 12 months for all domains but showed some decline at 24 months. CONCLUSION: An intra-gastric balloon as an adjunct to a lifestyle support programme represents a safe and well-tolerated treatment approach in severely obese adolescents, with short-term effects on weight change. Improvements in psychosocial health, physical activity and cardiorespiratory fitness were maintained at 12 months, with varying results at 24 months.

Strength measures are better than muscle mass measures in predicting health-related outcomes in older people: time to abandon the term sarcopenia?

There is no clear consensus on definition, cut-points or standardised assessments of sarcopenia. We found a lower limb strength assessment was at least as effective in predicting balance, mobility and falls in 419 older people as muscle mass-based measures of sarcopenia. INTRODUCTION: There is currently no consensus on the definition, cut-points or standardised assessments of sarcopenia. This study aimed to investigate whether several published definitions of sarcopenia differentiate between older people with respect to important functional and health outcomes. METHODS: Four hundred nineteen community-living older adults (mean age 81.2 ± 4.5, 49 % female) completed assessments of body composition (dual-energy X-ray absorptiometry), strength, balance, mobility and disability. Falls were recorded prospectively for a year using monthly calendars. Sarcopenia was defined according to four skeletal mass-based definitions, two strength-based definitions (handgrip or knee extensor force) and a consensus algorithm (low mass and low strength or slow gait speed). Obesity was defined according to percentage fat mass or waist circumference. RESULTS: The four skeletal mass-based definitions varied considerably with respect to the percentage of participants classified as sarcopenic and their predictive accuracy for functional and health outcomes. The knee extension strength-based definition was equivalent to or better than the mass-based and consensus algorithm definitions; i.e. weaker participants performed poorly in tests of leaning balance, stepping reaction time, gait speed and mobility. They also had higher physiological fall risk scores and were 43 % more likely to fall at home than their stronger counterparts. Adding obesity to sarcopenia definitions identified participants with greater self-reported disability. CONCLUSIONS: A simple lower limb strength assessment was at least as effective in predicting balance, functional mobility and falls in older people as more expensive and time-consuming muscle mass-based measures. These findings imply that functional terms such as muscle weakness or motor impairment are preferable to sarcopenia.

Therapeutically relevant structural and functional mechanisms triggered by physical and cognitive exercise.

Physical and cognitive exercise may prevent or delay dementia in later life but the neural mechanisms underlying these therapeutic benefits are largely unknown. We examined structural and functional magnetic resonance imaging (MRI) brain changes after 6 months of progressive resistance training (PRT), computerized cognitive training (CCT) or combined intervention. A total of 100 older individuals (68 females, average age=70.1, s.d.±6.7, 55-87 years) with dementia prodrome mild cognitive impairment were recruited in the SMART (Study of Mental Activity and Resistance Training) Trial. Participants were randomly assigned into four intervention groups: PRT+CCT, PRT+SHAM CCT, CCT+SHAM PRT and double SHAM. Multimodal MRI was conducted at baseline and at 6 months of follow-up (immediately after training) to measure structural and spontaneous functional changes in the brain, with a focus on the hippocampus and posterior cingulate regions. Participants' cognitive changes were also assessed before and after training. We found that PRT but not CCT significantly improved global cognition (F(90)=4.1, P<0.05) as well as expanded gray matter in the posterior cingulate (Pcorrected <0.05), and these changes were related to each other (r=0.25, P=0.03). PRT also reversed progression of white matter hyperintensities, a biomarker of cerebrovascular disease, in several brain areas. In contrast, CCT but not PRT attenuated decline in overall memory performance (F(90)=5.7, P<0.02), mediated by enhanced functional connectivity between the hippocampus and superior frontal cortex. Our findings indicate that physical and cognitive training depend on discrete neuronal mechanisms for their therapeutic efficacy, information that may help develop targeted lifestyle-based preventative strategies.

"Enjoy glass of wine before eating:" a randomized trial to test the orexigenic effects of this advice in advanced cancer patients.

BACKGROUND: Because the extant literature suggests wine increases appetite, this study sought to determine whether this effect could be observed in advanced cancer patients with appetite loss. METHODS: Advanced cancer patients with self-reported loss of appetite were randomly assigned to white wine with ≤15 % alcohol content twice a day for 3-4 weeks versus a nutritional supplement, such as Boost® or Ensure®. Patients assigned to wine were encouraged to also take a nutritional supplement, whereas patients assigned to the nutritional supplement arm were told to abstain completely from alcohol. Patient-reported outcomes were captured with a validated questionnaire to assess the primary endpoint of appetite improvement. RESULTS: A total of 141 patients (118 evaluable) were enrolled. Twenty-eight patients (48 %) in the wine arm reported an improvement in appetite at some point during the treatment period, whereas 22 patients (37 %) assigned to the nutritional supplement arm also reported improvement (p = 0.35). Other appetite-related questions and questionnaire items showed no statistically significant differences between treatment arms. In both arms, approximately 9 % of patients achieved weight stability (p = 0.98); median survival was not statistically different. Both interventions were well tolerated. CONCLUSION: As prescribed in this trial, wine does not improve appetite or weight in advanced cancer patients.

Being overweight is associated with hippocampal atrophy: the PATH Through Life Study.

BACKGROUND: The prevalence of obesity has increased dramatically in the past two decades, with major implications for individual well-being, population health and the economy. Of particular concern is the risk obesity presents for brain health and its consequences in an ageing population. These associations and their time course are not well understood, particularly after middle age. The aim of this study was to investigate whether being overweight/obese or having an increasing body weight is associated with hippocampal atrophy in early old age. METHODS: Participants were 420 unimpaired (Mini-Mental State Examination >26) individuals aged 60-64 years, living in the community and taking part in a large prospective study of ageing over an 8 year follow-up. Magnetic resonance imaging scans were collected at three assessments and the hippocampus was manually traced by expert neuroscientists. Multi-level analyses assessing the relationship between body mass index (BMI) and hippocampal atrophy over 8 years while controlling for important covariates were conducted. RESULTS: Analyses showed that BMI was negatively associated with left (coefficient: -10.65 mm(3); s.e. 4.81; P=0.027) and right (coefficient: -8.18 mm(3); s.e. 4.91; P=0.097) hippocampal volume at the first assessment. Over the follow-up period, those with a higher BMI experienced greater hippocampal atrophy and more so in the left (P=0.001) than in the right (P=0.058) hippocampus. CONCLUSIONS: The findings from this study provide important evidence indicating that being overweight or obese is associated with poorer brain health. These results are consistent with those of previous animal and human studies and further stress the importance of reducing the rate of obesity through education, population health interventions and policy.

Impairment in instrumental activities of daily living with high cognitive demand is an early marker of mild cognitive impairment: the Sydney memory and ageing study.

BACKGROUND: Criteria for mild cognitive impairment (MCI) consider impairment in instrumental activities of daily living (IADL) as exclusionary, but cross-sectional studies suggest that some high-level functional deficits are present in MCI. This longitudinal study examines informant-rated IADL in MCI, compared with cognitively normal (CN) older individuals, and explores whether functional abilities, particularly those with high cognitive demand, are predictors of MCI and dementia over a 2-year period in individuals who were CN at baseline. METHOD: A sample of 602 non-demented community dwelling individuals (375 CN and 227 with MCI) aged 70-90 years underwent baseline and 24-month assessments that included cognitive and medical assessments and an interview with a knowledgeable informant on functional abilities with the Bayer Activities of Daily Living Scale. RESULTS: Significantly more deficits in informant-reported IADL with high cognitive demand were present in MCI compared with CN individuals at baseline and 2-year follow-up. Functional ability in CN individuals at baseline, particularly in activities with high cognitive demand, predicted MCI and dementia at follow-up. Difficulties with highly cognitively demanding activities specifically predicted amnestic MCI but not non-amnestic MCI whereas those with low cognitive demand did not predict MCI or dementia. Age, depressive symptoms, cardiovascular risk factors and the sex of the informant did not contribute to the prediction. CONCLUSIONS: IADL are affected in individuals with MCI, and IADL with a high cognitive demand show impairment predating the diagnosis of MCI. Subtle cognitive impairment is therefore likely to be a major hidden burden in society.

Prevalence and characteristics of depression in mild cognitive impairment: the Sydney Memory and Ageing Study.

OBJECTIVE: Depression might be a risk factor for dementia. However, little is known about the prevalence of depressive symptoms in mild cognitive impairment (MCI) and whether mood or motivation-related symptoms are predominant. METHOD: A total of 767 non-demented community-dwelling adults aged 70-90 years completed a comprehensive assessment, including neuropsychological testing, and a past psychiatric/medical history interview. Depressive symptoms were assessed using the Geriatric Depression Scale (GDS) and Kessler Psychological Distress Scale (K10). Exploratory factor analysis was performed on the GDS and K10 to derive 'mood' and 'motivation' subscales. RESULTS: A total of 290 participants were classified as having MCI and 468 as cognitively normal (CN). Participants with MCI reported more depressive symptoms, and more MCI participants met the cut-off for clinically significant symptoms, relative to CN participants. Those with amnestic MCI (aMCI), but not non-amnestic MCI, had more depressive symptoms and were more likely to meet the cut-off for clinically significant depressive symptoms, relative to CN participants. Participants with MCI reported more mood-related symptoms than CN participants, while there were no differences between groups on motivation-related symptoms. CONCLUSION: Individuals with MCI, especially aMCI, endorse more depressive symptoms when compared with cognitively intact individuals. These findings highlight the importance of assessing and treating depressive symptoms in MCI.

Relationships between serum vitamin D levels, neuromuscular and neuropsychological function and falls in older men and women.

UNLABELLED: Among 463 community dwellers aged 70-90 years, those with vitamin D insufficiency showed reduced neuromuscular function, balance control and stepping ability and performed worse in tests of cognitive function. In men, vitamin D insufficiency was associated with an increased risk of falling. INTRODUCTION: The purpose of this study was to investigate the relationship between serum 25-hydroxy vitamin D (serum 25OHD) levels, physiological and neuropsychological function in older people, and to examine the relationship between serum 25OHD and prospective falls. METHODS: Four hundred sixty-three community-dwelling people aged 70-90 years underwent an assessment of physiological and neuropsychological performance and structured interviews relating to comorbidity and disability. Fall frequency during the 12 months follow-up was monitored with monthly falls diaries. RESULTS: Twenty-one percent of the men and 44% of the women were vitamin D insufficient (serum 25OHD ≤ 50 nmol/L). Participants with vitamin D insufficiency had weaker upper and lower limb strength, slower simple finger press and choice stepping reaction time, poorer leaning balance and slower gait speed, after controlling for age and body mass index, and, poorer executive function and visuospatial ability, after controlling for age and education. Vitamin D insufficiency significantly increased the rate of falls in men (IRR = 1.94, 95% CI = 1.19-3.15, p = 0.008) but not in women. CONCLUSIONS: These findings highlight the associations between vitamin D insufficiency and impairments in physiological and neuropsychological function that predispose older people to fall. The significant relationship between vitamin D insufficiency and falls found in the men may relate to the stronger association found between serum 25OHD levels and dynamic balance measures evident in this male population.

Dietary Patterns and Cognitive Health in Older Adults: Findings from the Sydney Memory and Ageing Study.

OBJECTIVES: Systematic reviews report dietary patterns may be associated with cognitive health in older adults. However, inconsistent findings have been reported and relevant research lacks large scale studies. This study aims to examine the associations of dietary patterns and cognitive function among older adults in an Australian ageing cohort. DESIGN: A population-based, cross-sectional analysis of the baseline phase of the Sydney Memory and Ageing Study, a well-characterised Australian ageing study. SETTING: The Sydney Memory and Ageing Study was initiated in 2005 to examine the clinical characteristics and prevalence of mild cognitive impairment (MCI). PARTICIPANTS: Non-demented community-dwelling individuals from English-speaking background (N = 819) aged 70-90 recruited from two areas of Sydney, following a random approach to 8914 individuals on the electoral roll in the Sydney Memory and Ageing study. MEASUREMENTS: The Cancer Council of Victoria Food Frequency Questionnaire was used to assess dietary intake. Scores for Mediterranean diet, Dietary Approaches to Stop Hypertension (DASH) diet and the Dietary Guidelines Index (DGI 2013) were generated. Two patterns - a Prudent healthy and a Western dietary pattern - were derived using principal components analysis (PCA). Neuropsychological tests were used to assess global cognition and six cognitive domains. Multivariate linear modelling assessed the relationship between dietary patterns and cognitive domain scores. RESULTS: Mediterranean diet and DASH diet were both positively linked to visuospatial cognition (P=0.002 and P=0.001 respectively). Higher intake of legumes and nuts was related to better performance in global cognition (ß=0.117; 95% CI:0.052, 0.181; P<0.001) and language and visuospatial cognitive domains. The Prudent healthy diet was associated with better global cognition (ß=0.307; 95% CI: 0.053, 0.562; P=0.019) in women and a Western diet was related to poorer global function (ß=-0.242; 95% CI: -0.451,-0.034; P=0.023) and executive function (ß=-0.325; 95% CI: -0.552,-0.099; P=0.005) in men. CONCLUSION: In this analysis, higher adherence to the Mediterranean diet, DASH diet, Prudent healthy diet and greater consumption of legumes and nuts were associated with better cognition among older adults.

A phase II trial of triapine (NSC# 663249) and gemcitabine as second line treatment of advanced non-small cell lung cancer: Eastern Cooperative Oncology Group Study 1503.

BACKGROUND: The objective of ECOG 1503 was to determine the response rate of this combination in the second-line treatment of advanced NSCLC. METHODS: Triapine 105 mg/m(2) IV on days 1, 8, and 15, and gemcitabine 1,000 mg/m(2) on days 1, 8, and 15, of a 28 day cycle. RESULTS: Eighteen patients enrolled. Three patients were not eligible due to protocol violations. No objective antitumor responses were seen. Three patients (20%) experienced stable disease (90% CI 5.7-44%). Median overall survival: 5.4 months (95% CI 4.2-11.6 months); median time to progression: 1.8 months (95% CI 1.7-3.5 months). Five patients developed acute infusion reactions to Triapine related to elevated methemoglobinemia. Patients with MDR1 variant genotypes of C3435T experienced superior overall survival compared to non-variants (13.3 vs. 4.3 months, respectively, p = 0.023). CONCLUSION: This regimen did not demonstrate activity in relapsed NSCLC. Prolonged survival seen with MDR1 variant genotypes is hypothesis-generating.