Design effect in multicenter studies: gain or loss of power?

<p>Abstract</p> <p>Background</p> <p>In a multicenter trial, responses for subjects belonging to a common center are correlated. Such a clustering is usually assessed through the design effect, defined as a ratio of two variances. The aim of this work was to describe and understand situations where the design effect involves a gain or a loss of power.</p> <p>Methods</p> <p>We developed a design effect formula for a multicenter study aimed at testing the effect of a binary factor (which thus defines two groups) on a continuous outcome, and explored this design effect for several designs (from individually stratified randomized trials to cluster randomized trials, and for other designs such as matched pair designs or observational multicenter studies).</p> <p>Results</p> <p>The design effect depends on the intraclass correlation coefficient (ICC) (which assesses the correlation between data for two subjects from the same center) but also on a statistic <it>S</it>, which quantifies the heterogeneity of the group distributions among centers (thus the level of association between the binary factor and the center) and on the degree of global imbalance (the number of subjects are then different) between the two groups. This design effect may induce either a loss or a gain in power, depending on whether the <it>S </it>statistic is respectively higher or lower than 1.</p> <p>Conclusion</p> <p>We provided a global design effect formula applying for any multicenter study and allowing identifying factors – the ICC and the distribution of the group proportions among centers – that are associated with a gain or a loss of power in such studies.</p

Le Cancer du sein (effets indésirables des protocoles thérapeutiques)

Le cancer du sein est une tumeur maligne de la glande mammaire, le plus fréquent des cancers féminins. Le traitement en est lourd, exigeant souvent à la fois radiothérapie, chimiothérapie et également chirurgie thérapeutique et reconstructrice. De nombreuses séquelles cutanées et de la fatigue sont induites après ces traitements anti-cancéreux. Les patientes ont alors un grand besoin de reconstruction mentale et physique par des moyens doux J ai réalisé une enquête (de mai à novembre 2012) à la station thermale de La Roche-Posay (86) afin de mettre en évidence les bienfaits du thermalisme dans l amélioration des séquelles induites par les différents protocoles thérapeutiques. Les vertus physico-chimiques des eaux thermales font partie intégrante des différents soins (douche filiforme, pulvérisation faciale/générale/buccale, douche gingivale, bain et massage). Le changement d environnement et la prise en charge globale de la personne durant les trois semaines de cure thermale contribuent au ressourcement et au bien-être du curiste. La cure thermale leur est apparue alors comme un relais naturel, sans effet secondaire, face aux traitements souvent lourds et fragilisants. La cure thermale post-cancer est donc une nouvelle approche thérapeutique pertinente pour accompagner dans la récupération cutanée et psychologique après un traitement anti-cancéreux, dans un environnement non hospitalier, plus serein.TOURS-BU Sciences Pharmacie (372612104) / SudocSudocFranceF

The impact of 3-year changes in lifestyle habits on metabolic syndrome parameters: the D.E.S.I.R study.: Metabolic syndrome, 3-y lifestyle changes

BACKGROUND: The effect of lifestyle changes in cohorts of free-living populations has been surprisingly little evaluated. DESIGN: A longitudinal study. METHODS: In the French Data from an Epidemiological Study on the Insulin Resistance (D.E.S.I.R) study of 1958 men and 2028 women, aged 30-65 years, the impact of 3-year changes in lifestyle habits (sporting activity, physical activity at home and at work, alcohol drinking, smoking) on metabolic syndrome parameters [insulin, glucose, high-density lipoprotein (HDL) cholesterol, triglycerides, systolic blood pressure, waist circumference] and on body mass index (BMI) were investigated. RESULTS: In men, 3-year increases in sporting activity were associated with a lowering of insulin, glucose, systolic blood pressure and waist circumference (all P < 0.05). For women, the only effect was on lowering waist circumference (P < 0.03). Increases in physical activity at home were beneficially associated with HDL-cholesterol, triglycerides, waist circumference and BMI changes (all P < 0.05) in men, but had no apparent effect in women. Decreases in alcohol intake only had an effect in men, with decreases in HDL-cholesterol and systolic blood pressure (P < 0.05), whereas decreasing cigarette smoking in men was associated with significant increases in insulin, glucose, triglycerides, waist and BMI (P < 0.001), and in women HDL-cholesterol, waist circumference and BMI increased (P < 0.02). These results were mainly caused by those who had stopped smoking. CONCLUSIONS: Increases in physical activity over the 3-year period were associated with beneficial effects on syndrome parameters, particularly in men. Smoking cessation and alcohol moderation produced mixed effects on these parameters

The Pattern of Brain Amyloid Load in Posterior Cortical Atrophy Using 18F-AV45: Is Amyloid the Principal Actor in the Disease

Background: Posterior cortical atrophy (PCA) is characterized by progressive higher-order visuoperceptual dysfunction and praxis declines. This syndrome is related to a number of underlying diseases, including, in most cases, Alzheimer's disease (AD). The aim of this study was to compare the amyloid load with 18F-AV45 positron emission tomography (PET) between PCA and AD subjects. Methods: We performed 18F-AV45 PET, cerebrospinal fluid (CSF) biomarker analysis and a neuropsychological assessment in 11 PCA patients and 12 AD patients. Results: The global and regional 18F-AV45 uptake was similar in the PCA and AD groups. No significant correlation was observed between global 18F-AV45 uptake and CSF biomarkers or between regional 18F-AV45 uptake and cognitive and affective symptoms. Conclusion: This 18F-AV45 PET amyloid imaging study showed no specific regional pattern of cortical 18F-AV45 binding in PCA patients. These results confirm that a distinct clinical phenotype in amnestic AD and PCA is not related to amyloid distribution

Total protein level in cerebrospinal fluid is stable in elderly adults

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Precuneus and Cingulate Cortex Atrophy and Hypometabolism in Patients with Alzheimer’s Disease and Mild Cognitive Impairment: MRI and 18F-FDG PET Quantitative Analysis Using FreeSurfer

International audienceOBJECTIVE:The objective of this study was to compare glucose metabolism and atrophy, in the precuneus and cingulate cortex, in patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI), using FreeSurfer.METHODS:47 individuals (17 patients with AD, 17 patients with amnestic MCI, and 13 healthy controls (HC)) were included. MRI and PET images using (18)F-FDG (mean injected dose of 185 MBq) were acquired and analyzed using FreeSurfer to define regions of interest in the hippocampus, amygdala, precuneus, and anterior and posterior cingulate cortex. Regional volumes were generated. PET images were registered to the T1-weighted MRI images and regional uptake normalized by cerebellum uptake (SUVr) was measured.RESULTS:Mean posterior cingulate volume was reduced in MCI and AD. SUVr were different between the three groups: mean precuneus SUVr was 1.02 for AD, 1.09 for MCI, and 1.26 for controls (p < 0.05); mean posterior cingulate SUVr was 0.96, 1.06, and 1.22 for AD, MCI, and controls, respectively (p < 0.05).CONCLUSION:We found graduated hypometabolism in the posterior cingulate cortex and the precuneus in prodromal AD (MCI) and AD, whereas atrophy was not significant. This suggests that the use of (18)F-FDG in these two regions could be a neurodegenerative biomarker

Brain Tissue Pulsatility is Increased in Midlife Depression: a Comparative Study Using Ultrasound Tissue Pulsatility Imaging

International audienceCerebrovascular disease (CVD) is consistently associated with late-life depression but poorly documented in midlife depression. It can be hypothesized that the relatively low sensitivity of conventional neuroimaging techniques does not allow the detection of subtle CVD in midlife depression. We used tissue pulsatility imaging (TPI), a novel ultrasound (US) neuroimaging technique that has demonstrated good sensitivity to detect changes in the pulsatility of small brain volumes, to identify early and subtle changes in brain vascular function in midlife depression. We compared the maximum and mean brain tissue pulsatility (MaxBTP and MeanBTP), as identified by TPI, between three groups of middle-aged females matched for age: patients with depression (n = 25), patients with remitted depression (n = 24) and community controls (n = 25). MRI arterial spin labeling, white matter hyperintensities (WMHs) and transcranial doppler (TCD) were used as control conventional markers for CVD. We found no difference in the MRI and TCD measures among the three groups. In contrast, depressive patients showed an increased BTP related to the mean global brain pulsatility (MeanBTP) and no change related to large vessels (MaxBTP) in comparison with the remitted and control groups. US neuroimaging is a highly accurate method to detect brain pulsatility changes related to cerebrovascular functioning, and TPI identified an increased BTP in midlife depressed patients, suggesting early and subtle vascular impairments in this population at risk for CVD such as stroke or WMHs. Because high pulsatility could represent prodromal cerebrovascular changes that damage the brain over time, this paper provides a potential target for blocking the progression of CVD

: Ein Prototyp der transienten Hochfrequenz-Elastografie zur Beurteilung der Haut (Dermis) -Fibrose: Eine diagnostische Studie bei Patienten mit venöser Insuffizienz und Kontrollprobanden

International audiencePurpose: High-frequency transient elastography (HF-TE) is a noninvasive technique for assessing shear-wave speed and finally elasticity in thin tissue such as the skin. It has never been validated for monitoring fibrotic skin diseases. The purpose was to evaluate the potential of HF-TE to assess skin fibrosis in patients with chronic venous disorders (CVD).Materials and methods: This clinical study enrolled 48 patients at various stages of CVD and 48 paired healthy volunteers. Subjects underwent a clinical examination with an evaluation of Rodnan's fibrosis skin score. We studied the dermis thickness measured using ultrasound (US) and elasticity measurements using cutometer and HF-TE studied according to 3 cutaneous zones positioned on the leg. The area under the receiver operating characteristic curve (AUC) was calculated to evaluate the diagnosis performance for a combined parameter (PRL) based on a logistic regression model using both elasticity and dermal thickness.Results: Patients with CVD had significantly higher values of skin elasticity than healthy subjects, 134.5 kPa and 132.1 kPa vs. 91.3 kPa, respectively. The dermis thickness also increased with escalation in CVD stage for all studied zones. The PRL parameter had an AUC value of 0.79 for all zones and stages of CVD clustered. The discriminating power of PRL increased with escalation of the CVD stage; with an AUC value of up to 0.89 for evolved stages, and a sensitivity and specificity of 0.79 and 0.89, respectively.Conclusion: HF-TE, coupled with a US measurement of dermis thickness, made it possible to propose a new biomarker, which proved to be a good diagnostic tool for skin fibrosis.Trial registration: ClinicalTrials.gov NCT02061254