Life-course socioeconomic environment and health risk behaviours: a multilevel small-area analysis of young-old persons in an urban neighbourhood in Lausanne, Switzerland

With a life expectancy at the age of 65 of around 20 years, damaging health risk behaviours of young-old adults have become a target for preventive actions. Such risk factors necessitate an accurate understanding of the present and past socioeconomic conditions associated with health risk behaviours. The aim of our study is to assess the impact of certain life events as well as economic and environmental factors on health risk behaviours. We included 1309 participants of the Lausanne Cohort Lc65+ aged 65-70 years and employed logistic regression analyses, with individuals nested within areas. The results illustrate the influences of socioeconomic factors from childhood to young-old age. Life experiences in adulthood and economic resources in young-old age are both associated with unfavourable health behaviours. Neighbourhood is a modest determinant as well, particularly regarding alcohol consumption. Therefore, prevention against health risk behaviours should focus on population subgroups defined on the basis of their socioeconomic and living contexts.

hMMP9 as predictive factor for response and progression free survival in breast cancer patients treated with bevacizumab and pegylated liposomal doxorubicin (PLD)

Background: The anti-angiogenic drug, bevacizumab (Bv), is currently used in the treatment of different malignancies including breast cancer. Many angiogenesis-associated molecules are found in the circulation of cancer patients. Until now, there are no prognostic or predictive factors identified in breast cancer patients treated with Bv. We present here the first results of the prospective monitoring of 6 angiogenesis-related molecules in the peripheral blood of breast cancer patients treated with a combination of Bv and PLD in the phase II trial, SAKK 24/06. Methods: Patients were treated with PLD (20 mg/m2) and Bv (10 mg/kg) on days 1 and 15 of each 4-week cycle for a maximum of 6 cycles, followed by Bv monotherapy maintenance (10 mg/m2 q2 weeks) until progression or severe toxicity. Plasma and serum samples were collected at baseline, after 2 months of therapy, then every 3 months and at treatment discontinuation. Enzyme-linked immunosorbent assays (Quantikine, R&D Systems and Reliatech) were used to measure the expression levels of human vascular endothelial growth factor (hVEGF), placental growth factor (hPlGF), matrix metalloproteinase 9 (hMMP9) and soluble VEGF receptors hsVEGFR-1, hsVEGFR-2 and hsVEGFR-3. The log-transformed data (to reduce the skewness) for each marker was analyzed using an analysis of variance (ANOVA) model to determine if there was a difference between the mean of the subgroups of interest (where α = 0.05). The untransformed data was also analyzed in the same manner as a "sensitivity" check. Results: 132 blood samples were collected in 41 out of 43 enrolled patients. Baseline levels of the molecules were compared to disease status according to RECIST. There was a statistically significant difference in the mean of the log-transformed levels of hMMP9 between responders [CR+PR] versus the mean in patients with PD (p-value=0.0004, log fold change=0.7536), and between patients with disease control [CR+PR+SD] and those with PD (p-value=<0.0001, log fold change=0.81559), with the log-transformed level of hMMP9 being higher for the responder group. The mean of the log-transformed levels of hsVEGFR-1 was statistically significantly different between patients with disease control [CR+PR+SD] and those with PD (p-value=0.0068, log fold change=-0.6089), where the log-transformed level of hsVEGFR-1 was lower for the responder group. The log-transformed level of hMMP9 at baseline was identified as a significant prognostic factor in terms of progression free survival (PFS): p-value=0.0417, hazard ratio (HR)=0.574 with a corresponding 95% confidence interval (0.336 - 0.979)). No strong correlation was shown either between the log-transformed levels of hsVEGF, hPlGF, hsVEGFR-2 or hsVEGFR-3 and clinical response or the occurrence of severe toxicity, or between the levels of the different molecules. Conclusions: Our results suggest that baseline plasma level of the matrix metalloproteinase, hMMP9, could predict tumor response and PFS in patients treated with a combination of Bv and PLD. These data justify further investigation in breast cancer patients treated with anti-angiogenic therapy.

Lenalidomide maintenance after stem-cell transplantation for multiple myeloma.

BACKGROUND: High-dose chemotherapy with autologous stem-cell transplantation is a standard treatment for young patients with multiple myeloma. Residual disease is almost always present after transplantation and is responsible for relapse. This phase 3, placebo-controlled trial investigated the efficacy of lenalidomide maintenance therapy after transplantation. METHODS: We randomly assigned 614 patients younger than 65 years of age who had nonprogressive disease after first-line transplantation to maintenance treatment with either lenalidomide (10 mg per day for the first 3 months, increased to 15 mg if tolerated) or placebo until relapse. The primary end point was progression-free survival. RESULTS: Lenalidomide maintenance therapy improved median progression-free survival (41 months, vs. 23 months with placebo; hazard ratio, 0.50; P<0.001). This benefit was observed across all patient subgroups, including those based on the β(2)-microglobulin level, cytogenetic profile, and response after transplantation. With a median follow-up period of 45 months, more than 70% of patients in both groups were alive at 4 years. The rates of grade 3 or 4 peripheral neuropathy were similar in the two groups. The incidence of second primary cancers was 3.1 per 100 patient-years in the lenalidomide group versus 1.2 per 100 patient-years in the placebo group (P=0.002). Median event-free survival (with events that included second primary cancers) was significantly improved with lenalidomide (40 months, vs. 23 months with placebo; P<0.001). CONCLUSIONS: Lenalidomide maintenance after transplantation significantly prolonged progression-free and event-free survival among patients with multiple myeloma. Four years after randomization, overall survival was similar in the two study groups. (Funded by the Programme Hospitalier de Recherche Clinique and others; ClinicalTrials.gov number, NCT00430365.).

L'endocardite en pratique ambulatoire [Infective endocarditis and outpatient practice].

The incidence of infectious endocarditis is fairly stable over the past decades. It is estimated at roughly 3-4 case per patient-year. However, as a consequence of medical progress, Staphylococcus aureus endocarditis has become more prevalent. This is particularly true for health-care associated endocarditis, especially in iv-drug abusers or hemodialysis patients. Mortality (15-20% of patients in the last series) remains high. About 50% of patients undergo surgical treatment, whereas outpatient therapy is more and more frequent for highly selected subgroups of patients without complications and infected with low-risk organims. The present paper reviews in detail the epidemiology of infective endocarditis and discuss in detail the different out-patients therapies.

Field Data Acquisition Technologies for Iowa Transportation Agencies, HR-366 August 1994

This report describes the results of the research project investigating the use of advanced field data acquisition technologies for lowa transponation agencies. The objectives of the research project were to (1) research and evaluate current data acquisition technologies for field data collection, manipulation, and reporting; (2) identify the current field data collection approach and the interest level in applying current technologies within Iowa transportation agencies; and (3) summarize findings, prioritize technology needs, and provide recommendations regarding suitable applications for future development. A steering committee consisting oretate, city, and county transportation officials provided guidance during this project. Technologies considered in this study included (1) data storage (bar coding, radio frequency identification, touch buttons, magnetic stripes, and video logging); (2) data recognition (voice recognition and optical character recognition); (3) field referencing systems (global positioning systems [GPS] and geographic information systems [GIs]); (4) data transmission (radio frequency data communications and electronic data interchange); and (5) portable computers (pen-based computers). The literature review revealed that many of these technologies could have useful applications in the transponation industry. A survey was developed to explain current data collection methods and identify the interest in using advanced field data collection technologies. Surveys were sent out to county and city engineers and state representatives responsible for certain programs (e.g., maintenance management and construction management). Results showed that almost all field data are collected using manual approaches and are hand-carried to the office where they are either entered into a computer or manually stored. A lack of standardization was apparent for the type of software applications used by each agency--even the types of forms used to manually collect data differed by agency. Furthermore, interest in using advanced field data collection technologies depended upon the technology, program (e.g.. pavement or sign management), and agency type (e.g., state, city, or county). The state and larger cities and counties seemed to be interested in using several of the technologies, whereas smaller agencies appeared to have very little interest in using advanced techniques to capture data. A more thorough analysis of the survey results is provided in the report. Recommendations are made to enhance the use of advanced field data acquisition technologies in Iowa transportation agencies: (1) Appoint a statewide task group to coordinate the effort to automate field data collection and reporting within the Iowa transportation agencies. Subgroups representing the cities, counties, and state should be formed with oversight provided by the statewide task group. (2) Educate employees so that they become familiar with the various field data acquisition technologies.

Influence des habitudes alimentaires sur la morbidité chez 645 patients obèses d'une consultation spécialisée. [Effect of eating habits on morbidity in 645 patients at a specialized clinic].

Among 645 obese patients examined at an out-patient clinic for obese patients by physical examination and a computerized questionnaire, two subgroups of patients could be identified according to their nutritional preferences: 177 patients preferred carbohydrates exclusively (group A) and 73 patients fat exclusively (group B). No definite preferences were formulated by the other patients. Among patients under 25 years, only 3 belonged to group B and 49 to group A, while in older patients no significant differences were found. Among patients with BMI less than 30, there were significantly fewer patients from group B than from group A (p = 0.006), while in patients with BMI greater than 30 no significant difference was observed. There were significantly more men in group B than in group A. 57% of the patients of group B complained of physical symptoms related to their obesity, compared to 37% in group A (p = 0.006). 26% of group B suffered from joints and muscles compared to 13% of group A (p = 0.003). Hyperglycemia (greater than 5,6 mmol/l) was found in 21% of group A and in 40% of group B (p less than 0.005). Hypercholesterolemia (greater than 6.5 mmol/l) was found in 20% of group A and in 32% of group B (p less than 0.05). In conclusion, obese patients who prefer fat have more general symptoms related to obesity, more abnormal physical signs, and more frequently have hyperglycemia and hypercholesterolemia than patients who prefer carbohydrates.

Survival impact of lung transplantation for COPD.

Chronic obstructive pulmonary disease (COPD) is the primary indication for lung transplantation (LTx), but survival benefit is still under debate. We analysed the survival impact of LTx in COPD with a new approach, using the BODE (body mass index, airway obstruction, dyspnoea, exercise capacity) index. We retrospectively reviewed 54 consecutive lung transplants performed for COPD. The pre-transplant BODE score was calculated for each patient and a predicted survival was derived from the survival functions of the original BODE index validation cohort. Predicted and observed post-transplant survival was then compared. In the subgroups with a BODE score >or=7 and <7, a majority of patients (66% and 69%, respectively) lived for longer after LTx than predicted by their individual BODE index. The median survival was significantly improved in the entire cohort and in the subgroup with a BODE score >or=7. 4 yrs after LTx a survival benefit was only apparent in patients with a pre-transplant BODE score of >or=7. In conclusion, while a majority of COPD patients had an individual survival benefit from LTx regardless of their pre-transplant BODE score, a global survival benefit was seen only in patients with more severe disease. This supports the use of the BODE index as a selection criteria for LTx candidates.

Clinical Disease Severity of Respiratory Viral Co-Infection versus Single Viral Infection: A Systematic Review and Meta-Analysis.

BACKGROUND: Results from cohort studies evaluating the severity of respiratory viral co-infections are conflicting. We conducted a systematic review and meta-analysis to assess the clinical severity of viral co-infections as compared to single viral respiratory infections. METHODS: We searched electronic databases and other sources for studies published up to January 28, 2013. We included observational studies on inpatients with respiratory illnesses comparing the clinical severity of viral co-infections to single viral infections as detected by molecular assays. The primary outcome reflecting clinical disease severity was length of hospital stay (LOS). A random-effects model was used to conduct the meta-analyses. RESULTS: Twenty-one studies involving 4,280 patients were included. The overall quality of evidence applying the GRADE approach ranged from moderate for oxygen requirements to low for all other outcomes. No significant differences in length of hospital stay (LOS) (mean difference (MD) -0.20 days, 95% CI -0.94, 0.53, p = 0.59), or mortality (RR 2.44, 95% CI 0.86, 6.91, p = 0.09) were documented in subjects with viral co-infections compared to those with a single viral infection. There was no evidence for differences in effects across age subgroups in post hoc analyses with the exception of the higher mortality in preschool children (RR 9.82, 95% CI 3.09, 31.20, p<0.001) with viral co-infection as compared to other age groups (I2 for subgroup analysis 64%, p = 0.04). CONCLUSIONS: No differences in clinical disease severity between viral co-infections and single respiratory infections were documented. The suggested increased risk of mortality observed amongst children with viral co-infections requires further investigation.

Stages of change, barriers, benefits, and preferences for exercise in RA patients: a cross-sectional study.

OBJECTIVES: To determine the distribution of exercise stages of change in a rheumatoid arthritis (RA) cohort, and to examine patients' perceptions of exercise benefits, barriers, and their preferences for exercise. METHODS: One hundred and twenty RA patients who attended the Rheumatology Unit of a University Hospital were asked to participate in the study. Those who agreed were administered a questionnaire to determine their exercise stage of change, their perceived benefits and barriers to exercise, and their preferences for various features of exercise. RESULTS: Eighty-nine (74%) patients were finally included in the analyses. Their mean age was 58.4 years, mean RA duration 10.1 years, and mean disease activity score 2.8. The distribution of exercise stages of change was as follows: precontemplation (n = 30, 34%), contemplation (n = 11, 13%), preparation (n = 5, 6%), action (n = 2, 2%), and maintenance (n = 39, 45%). Compared to patients in the maintenance stage of change, precontemplators exhibited different demographic and functional characteristics and reported less exercise benefits and more barriers to exercise. Most participants preferred exercising alone (40%), at home (29%), at a moderate intensity (64%), with advice provided by a rheumatologist (34%) or a specialist in exercise and RA (34%). Walking was by far the preferred type of exercise, in both the summer (86%) and the winter (51%). CONCLUSIONS: Our cohort of patients with RA was essentially distributed across the precontemplation and maintenance exercise stages of change. These subgroups of patients exhibit psychological and functional differences that make their needs different in terms of exercise counselling.

First consumption ever of multiple substances: applying an expert-based taxonomy to a Swiss national sample of adolescents.

The use of multiple legal and illegal substances by adolescents is a growing concern in all countries, but since no consensus about a taxonomy did emerge yet, it is difficult to understand the different patterns of consumption and to implement tailored prevention and treatment programs directed towards specific subgroups of the adolescent population. Using data from a Swiss survey on adolescent health, we analyzed the age at which ten legal and illegal substances were consumed for the first time ever by applying a method combining the strength of both automatic clustering and use of substance experts. Results were then compared to 30 socio-economic factors to establish the usefulness of and to validate our taxonomy. We also analyzed the succession of substance first use for each group. The final taxonomy consists of eight groups ranging from non-consumers to heavy drug addicts. All but four socio-economic factors were significantly associated with the taxonomy, the strongest associations being observed with health, behavior, and sexuality factors. Numerous factors influence adolescents in their decision to first try substances or to use them on a regular basis, and no factor alone can be considered as an absolute marker of problematic behavior regarding substance use. Different processes of experimentation with substances are associated with different behaviors, therefore focusing on only one substance or only one factor is not efficient. Prevention and treatment programs can then be tailored to address specific issues related to different youth subgroups.

Clinical Implications of CD8+ T-cell infiltration in frequent and rare cancers.

Recent studies of cancer patients revealed high diversity in oncogenic mechanisms, leading to increased treatment individualization for subgroups of patients with frequent cancers. A similar development may not be possible for patients with rare cancers, such as Merkel cell carcinoma (MCC). Finding shared disease mechanisms may open new options to understanding and treating such tumors. Tumor-infiltrating CD8+ T cells are frequently associated with favorable clinical outcome in a remarkably large spectrum of cancers. In this issue, Afanasiev et al. suggest a mechanism that may hinder the tumor homing of CD8+ T cells in MCC patients. It is possible that therapeutic mobilization of anti-cancer T cells may be useful in patients who share this specific immune biological feature.

The stomach cancer pooling (StoP) project: study design and presentation.

Gastric cancer affects about one million people per year worldwide, being the second leading cause of cancer mortality. The study of its etiology remains therefore a global issue as it may allow the identification of major targets, besides eradication of Helicobacter pylori infection, for primary prevention. It has however received little attention, given its comparatively low incidence in most high-income countries. We introduce a consortium of epidemiological investigations named the 'Stomach cancer Pooling (StoP) Project'. Twenty-two studies agreed to participate, for a total of over 9000 cases and 23 000 controls. Twenty studies have already shared the original data set. Of the patients, 40% are from Asia, 43% from Europe, and 17% from North America; 34% are women and 66% men; the median age is 61 years; 56% are from population-based case-control studies, 41% from hospital-based ones, and 3% from nested case-control studies derived from cohort investigations. Biological samples are available from 12 studies. The aim of the StoP Project is to analyze the role of lifestyle and genetic determinants in the etiology of gastric cancer through pooled analyses of individual-level data. The uniquely large data set will allow us to define and quantify the main effects of each risk factor of interest, including a number of infrequent habits, and to adequately address associations in subgroups of the population, as well as interaction within and between environmental and genetic factors. Further, we will carry out separate analyses according to different histotypes and subsites of gastric cancer, to identify potential different risk patterns and etiological characteristics.

Individual prediction of cognitive decline in mild cognitive impairment using support vector machine-based analysis of diffusion tensor imaging data.

Although cross-sectional diffusion tensor imaging (DTI) studies revealed significant white matter changes in mild cognitive impairment (MCI), the utility of this technique in predicting further cognitive decline is debated. Thirty-five healthy controls (HC) and 67 MCI subjects with DTI baseline data were neuropsychologically assessed at one year. Among them, there were 40 stable (sMCI; 9 single domain amnestic, 7 single domain frontal, 24 multiple domain) and 27 were progressive (pMCI; 7 single domain amnestic, 4 single domain frontal, 16 multiple domain). Fractional anisotropy (FA) and longitudinal, radial, and mean diffusivity were measured using Tract-Based Spatial Statistics. Statistics included group comparisons and individual classification of MCI cases using support vector machines (SVM). FA was significantly higher in HC compared to MCI in a distributed network including the ventral part of the corpus callosum, right temporal and frontal pathways. There were no significant group-level differences between sMCI versus pMCI or between MCI subtypes after correction for multiple comparisons. However, SVM analysis allowed for an individual classification with accuracies up to 91.4% (HC versus MCI) and 98.4% (sMCI versus pMCI). When considering the MCI subgroups separately, the minimum SVM classification accuracy for stable versus progressive cognitive decline was 97.5% in the multiple domain MCI group. SVM analysis of DTI data provided highly accurate individual classification of stable versus progressive MCI regardless of MCI subtype, indicating that this method may become an easily applicable tool for early individual detection of MCI subjects evolving to dementia.

Medulloblastomas in adults: prognostic factors and lessons from paediatrics.

Purpose of reviewMedulloblastomas are very rare in adults. Usual treatment consists of craniospinal radiation with or without chemotherapy. Current efforts focus on a better understanding of tumour biology, stratifying patients into risk groups and adapting treatment accordingly. This review discusses clinical and new molecular risk factors that will help to optimize treatment in adult medulloblastoma patients.Recent findingsThe clinical risk stratification should be complemented with new molecular prognostic markers. Gene-expression profiling has permitted identification of four to six molecular medulloblastoma subgroups. The WNT subgroup shows overexpression of genes of the WNT/wingless signalling pathway with frequent mutations of the CNNTB1 gene, loss of chromosome 6 and accumulation of nuclear beta-catenin, and is most often seen in children with medulloblastomas of classical histology. This variant has a good prognosis. Activation of the sonic hedgehog pathway with frequent mutations of the PTCH and SUFU genes, loss of 9q, and positivity for GLI1 and SFRP1 is more frequent in children less than 3 years old and in adults, commonly associated with desmoplastic histology. Other subgroups are not so well defined and have overlapping characteristics, but MYC/MYCN amplification, 17q gain and, large cell/anaplastic histology are factors of poor prognosis.SummaryNew molecular subgroups will help tailor treatment and further develop new targeted therapies. Prospective and ideally randomized trials should be performed in adults, including risk stratification by molecular markers, to identify optimal treatment for each risk group.

Spinal cord T-cell infiltration in the spared nerve injury model of neuropathic pain: a time course study

Background : Numerous studies have shown that immune cells infiltrate the spinal cord after peripheral nerve injury and that they play a major contribution to sensory hypersensitivity in rodents. In particular, the role of monocyte-derived cells and T lymphocytes seems to be prominent in this process. This exciting new perspective in research on neuropathic pain opens many different areas of work, including the understanding of the function of these cells and how they impact on neural function. However, no systematic description of the time course or cell types that characterize this infiltration has been published yet, although this seems to be the rational first step of an overall understanding of the phenomenon. Objective : Describe the time course and cell characteristics of T lymphocyte infiltration in the spinal cord in the Spared Nerve Injury (SNI) model of neuropathic pain in rats. Methods : Collect of lumbar spinal cords of rats at days 2, 7, 21 and 40 after SNI or sham operation (n=4). Immunofluorescence detecting different proteins of T cell subgroups (CD2+CD4+, CD2+CD8+, Th1 markers, Th2 markers, Th17 markers). Quantification of the infiltration rate of the different subgroups. Expected results : First, we expect to see an infiltration of T cells in the spinal cord ipsilateral to nerve injury, higher in SNI rats than in sham animals. Second, we anticipate that different subtypes of T cells penetrate at different time points. Finally, the number of T lymphocytes are expected to decrease at the latest time point, showing a resolution of the process underlying their infiltrating the spinal cord in the first place. Impact : A systematic description of the infiltration of T cells in the spinal cord after peripheral nerve injury is needed to have a better understanding of the role of immune cells in neuropathic pain. The time course that we want to establish will provide the scientific community with new perspectives. First, it will confirm that T cells do indeed infiltrate the spinal cord after SNI in rats. Second, the type of T cells infiltrating at different time points will give clues about their function, in particular their inflammatory or anti-inflammatory profile. From there on, other studies could be lead, investigating the functional side of the specific subtypes put to light by us. Ultimately, this could lead to the discovery of new drugs targeting T cells or their infiltration, in the hope of improving neuropathic pain.