Accuracy of four cardiovascular risk scores in a Swiss population-based cohort

Purpose: To assess the global cardiovascular (CV) risk of an individual, several scores have been developed. However, their accuracy and comparability need to be evaluated in populations others from which they were derived. The aim of this study was to compare the predictive accuracy of 4 CV risk scores using data of a large population-based cohort. Methods: Prospective cohort study including 4980 participants (2698 women, mean age± SD: 52.7±10.8 years) in Lausanne, Switzerland followed for an average of 5.5 years (range 0.2 - 8.5). Two end points were assessed: 1) coronary heart disease (CHD), and 2) CV diseases (CVD). Four risk scores were compared: original and recalibrated Framingham coronary heart disease scores (1998 and 2001); original PROCAM score (2002) and its recalibrated version for Switzerland (IAS-AGLA); Reynolds risk score. Discrimination was assessed using Harrell's C statistics, model fitness using Akaike's information criterion (AIC) and calibration using pseudo Hosmer-Lemeshow test. The sensitivity, specificity and corresponding 95% confidence intervals were assessed for each risk score using the highest risk category ([20+ % at 10 years) as the "positive" test. Results: Recalibrated and original 1998 and original 2001 Framingham scores show better discrimination (>0.720) and model fitness (low AIC) for CHD and CVD. All 4 scores are correctly calibrated (Chi2<20). The recalibrated Framingham 1998 score has the best sensitivities, 37.8% and 40.4%, for CHD and CVD, respectively. All scores present specificities >90%. Framingham 1998, PROCAM and IAS-AGLA scores include the greatest proportion of subjects (>200) in the high risk category whereas recalibrated Framingham 2001 and Reynolds include <=44 subjects. Conclusion: In this cohort, we see variations of accuracy between risk scores, the original Framingham 2001 score demonstrating the best compromise between its accuracy and its limited selection of subjects in the highest risk category. We advocate that national guidelines, based on independently validated data, take into account calibrated CV risk scores for their respective countries.

Prevalence of obesity and abdominal obesity in the Lausanne population.

BACKGROUND: Obesity can be defined using body mass index (BMI) or waist (abdominal obesity). Little information exists regarding its prevalence and determinants in Switzerland. Hence, we assessed the levels of obesity as defined by BMI or waist circumference in a Swiss population-based sample. METHODS: Cross-sectional, population-based non-stratified random sample of 3,249 women and 2,937 men aged 35-75 years living in Lausanne, Switzerland. Overall participation rate was 41%. RESULTS: In men, the prevalences of overweight (BMI > or =25 kg/m2) and obesity (BMI > or =30 kg/m2) were 45.5% and 16.9%, respectively, higher than in women (28.3% and 14.3%, respectively). The prevalence of abdominal obesity (waist > or =102 in men and > or =88 cm in women) was higher in women than in men (30.6% vs. 23.9%). Obesity and abdominal obesity increased with age and decreased with higher educational level in both genders. In women, the prevalence of obesity was lower among former and current smokers, whereas in men the prevalence of obesity was higher in former smokers but did not differ between current and never smokers. Multivariate analysis showed age to be positively related, and education and physical activity to be negatively related with obesity and abdominal obesity in both genders, whereas differential effects of smoking were found between genders. CONCLUSION: The prevalence of abdominal obesity is higher than BMI-derived obesity in the Swiss population. Women presented with more abdominal obesity than men. The association between smoking and obesity levels appears to differ between genders.

One-year prevalence of low back pain in two Swiss regions: estimates from the population participating in the 1992-1993 MONICA project.

STUDY DESIGN: A cross-sectional survey was performed. OBJECTIVE: To estimate the extent of low back pain as a public health problem. SUMMARY OF BACKGROUND DATA: Health surveys converge on very high estimates of low back pain in general populations, but few studies have included severity criteria in their definition and conclusions. Because it is unlikely that interventions will influence the prevalence of minimal and infrequent symptoms, greater attention should be paid to characteristics of low back pain that indicate some impact on the life of survey respondents. METHODS: Two regions participated in the MONICA (MONitoring of trends and determinants in CArdiovascular disease) project in Switzerland. Participants randomly selected from the general population completed a standard self-administered questionnaire on cardiovascular risk factors. A special section on low back pain was added in the third (1992-1993) MONICA survey and completed by 3227 participants. RESULTS: A regional difference found in the 12-month prevalence rate disappeared with the inclusion of severity criteria. Low back pain over more than seven cumulated days was reported among men by 20.2% (age range, 25-34 years) to 28.5% (age range, 65-74 years), respectively, among women by 31.1% to 38.5%. Similar rates of reduction in activity (professional, housekeeping, and leisure time) and medical consultation (conventional and nonconventional) motivated by low back pain characterized the two participating regions. The cumulative duration of pain was related to all the indicators showing the impact of low back pain on everyday life. CONCLUSIONS: Determining the cumulative duration of low back pain over the preceding year is a straightforward task, and a cutoff at 1 week seems appropriate for distinguishing between low- and high-impact low back pain.

Personalized care in neuro-oncology coming of age: why we need MGMT and 1p/19q testing for malignant glioma patients in clinical practice.

Histological subtyping and grading by malignancy are the cornerstones of the World Health Organization (WHO) classification of tumors of the central nervous system. They shall provide clinicians with guidance as to the course of disease to be expected and the choices of treatment to be made. Nonetheless, patients with histologically identical tumors may have very different outcomes, notably in patients with astrocytic and oligodendroglial gliomas of WHO grades II and III. In gliomas of adulthood, 3 molecular markers have undergone extensive studies in recent years: 1p/19q chromosomal codeletion, O(6)-methylguanine methyltransferase (MGMT) promoter methylation, and mutations of isocitrate dehydrogenase (IDH) 1 and 2. However, the assessment of these molecular markers has so far not been implemented in clinical routine because of the lack of therapeutic implications. In fact, these markers were considered to be prognostic irrespective of whether patients were receiving radiotherapy (RT), chemotherapy, or both (1p/19q, IDH1/2), or of limited value because testing is too complex and no chemotherapy alternative to temozolomide was available (MGMT). In 2012, this situation has changed: long-term follow-up of the Radiation Therapy Oncology Group 9402 and European Organisation for Research and Treatment of Cancer 26951 trials demonstrated an overall survival benefit from the addition to RT of chemotherapy with procarbazine/CCNU/vincristine confined to patients with anaplastic oligodendroglial tumors with (vs without) 1p/19q codeletion. Furthermore, in elderly glioblastoma patients, the NOA-08 and the Nordic trial of RT alone versus temozolomide alone demonstrated a profound impact of MGMT promoter methylation on outcome by therapy and thus established MGMT as a predictive biomarker in this patient population. These recent results call for the routine implementation of 1p/19q and MGMT testing at least in subpopulations of malignant glioma patients and represent an encouraging step toward the development of personalized therapeutic approaches in neuro-oncology.

How High Dose(s) of Oral Vitamin D3 Can Correct Insufficiency in a Non Supplemented Rheumatologic Population ?

Introduction: 700 to 1000 UI Vitamin D/day prevent 20% of fall and fracture. Higher dosage could prevent other health problems, such as immune diseases. Adherence to oral daily vitamin D supplementation is low. There is no guideline on how to supplement patients with rheumatic diseases. We evaluated if 1-2 dose(s) of 300'000 UI oral vitamin D3 was enough to reach an optimal level of 25-OH vitamin D in late winter in patients with insufficiency. Methods: During November 2009 (M0) patients attending our Rheumatology Outpatient Clinic had a blood test to measure 25-OH vitamin D. Results were classified as: deficiency <10µg/l, insufficiency 10µg/l to 30µg/l and normal >30µg/l. Patients on daily oral vitamin D3 or who received a single high dose of vitamin D3 in the last 6 months and patients with deficiency or normal results were excluded. Patients included received a single dose of 300'000 IU of oral vitamin D3 and were asked to come back for a blood test for 25-OH vitamin D after 3 (M3) and 6 months (M6). If they were still insufficient at M3, they received a second high dose of 300'000 IU of oral vitamin D3. Results: 292 patients had their level of 25-OH vitamin D determined at M0. 141 patients (70% women) had vitamin D insufficiency (18.5µg/l (10.2-29.1)) and received a prescription for a single dose of 300'000 IU of oral vitamin D3. Men and women were not statistically different in term of age and 25-OH vitamin D level at M0. 124/141 (88%) patients had a blood test at M3. 2/124 (2%) had deficiency (8.1µg/l (7.5-8.7)), 50/124 (40%) normal results (36.7µg/l (30.5-56.5)). 58% (72/124) were insufficient (23.6µg/l (13.8-29.8)) and received a second prescription for 300'000 IU of oral vitamin D3. Of the 50/124 patients who had normal results at M3 and did not receive a second prescription, 36 (72%) had a test at M6. 47% (17/36) had normal results (34.8µg/l (30.3-42.8)), 53% (19/36) were insufficient (25.6µg/l (15.2-29.9)). Out of the 54/72 (75%) patients who received a second prescription, 28/54 (52%) had insufficiency (23.2µg/l (12.8-28.7)) and 26/54 (48%) had normal results (33.8µg/l (30.0-43.7)) at M 6. Discussion: This real life study has shown that one or two oral bolus of 300'000 IU of vitamin D3 in autumn and winter was not enough to completely correct hypovitaminosis D but was a good way of preventing a nadir of 25-OH vitamin D usually observed in spring in a Swiss rheumatologic population.

Catch-up growth strategies differ between body structures: interactions between age and structure-specific growth in wild nestling Alpine swifts

1. Little is known on the occurrence and magnitude of faster than normal (catch-up) growth in response to periods of undernutrition in the wild, and the extent to which different body structures compensate and over what timescales is poorly understood. 2. We investigated catch-up growth in nestling Alpine Swifts, Apus melba, by comparing nestling growth trajectories in response to a naturally occurring 1-week period of inclement weather and undernutrition with growth of nestlings reared in a good year. 3. In response to undernutrition, nestlings exhibited a hierarchy of tissues preservation and compensation, with body mass being restored quickly after the end of the period of undernutrition, acceleration of skeletal growth occurring later in development, and compensation in wing length occurring mostly due to a prolongation of growth and delayed fledging. 4. The effect of undernutrition and subsequent catch-up growth was age-dependent, with older nestlings being more resilient to undernutrition, and in turn having less need to compensate later in the development. 5. This shows that young in a free-living bird population can compensate in body mass and body size for a naturally occurring period of undernutrition, and that the timing and extent of compensation varies with age and between body structures.

Alterations of the 5'untranslated region of SLC16A12 lead to age-related cataract.

PURPOSE. Knowledge of genetic factors predisposing to age-related cataract is very limited. The aim of this study was to identify DNA sequences that either lead to or predispose for this disease. METHODS. The candidate gene SLC16A12, which encodes a solute carrier of the monocarboxylate transporter family, was sequenced in 484 patients with cataract (134 with juvenile cataract, 350 with age-related cataract) and 190 control subjects. Expression studies included luciferase reporter assay and RT-PCR experiments. RESULTS. One patient with age-related cataract showed a novel heterozygous mutation (c.-17A>G) in the 5'untranslated region (5'UTR). This mutation is in cis with the minor G-allele of the single nucleotide polymorphism (SNP) rs3740030 (c.-42T/G), also within the 5'UTR. Using a luciferase reporter assay system, a construct with the patient's haplotype caused a significant upregulation of luciferase activity. In comparison, the SNP G-allele alone promoted less activity, but that amount was still significantly higher than the amount of the common T-allele. Analysis of SLC16A12 transcripts in surrogate tissue demonstrated striking allele-specific differences causing 5'UTR heterogeneity with respect to sequence and quantity. These differences in gene expression were mirrored in an allele-specific predisposition to age-related cataract, as determined in a Swiss population (odds ratio approximately 2.2; confidence intervals, 1.23-4.3). CONCLUSIONS. The monocarboxylate transporter SLC16A12 may contribute to age-related cataract. Sequences within the 5'UTR modulate translational efficiency with pathogenic consequences.

Forgoing dental care for economic reasons in Switzerland: a six-year cross-sectional population-based study

BACKGROUND: While oral health is part of general health and well-being, oral health disparities nevertheless persist. Potential mechanisms include socioeconomic factors that may influence access to dental care in the absence of universal dental care insurance coverage. We investigated the evolution, prevalence and determinants (including socioeconomic) of forgoing of dental care for economic reasons in a Swiss region, over the course of six years. METHODS: Repeated population-based surveys (2007-2012) of a representative sample of the adult population of the Canton of Geneva, Switzerland. Forgone dental care, socioeconomic and insurance status, marital status, and presence of dependent children were assessed using standardized methods. RESULTS: A total of 4313 subjects were included, 10.6% (457/4313) of whom reported having forgone dental care for economic reasons in the previous 12 months. The crude percentage varied from 2.4% in the wealthiest group (monthly income ≥ 13,000 CHF, 1 CHF ≈ 1$) to 23.5% among participants with the lowest income (<3,000 CHF). Since 2007/8, forgoing dental care remained stable overall, but in subjects with a monthly income of <3,000 CHF, the adjusted percentage increased from 16.3% in 2007/8 to 20.6% in 2012 (P trend = 0.002). Forgoing dental care for economic reasons was independently associated with lower income, younger age, female gender, current smoking, having dependent children, divorced status and not living with a partner, not having a supplementary health insurance, and receipt of a health insurance premium cost-subsidy. CONCLUSIONS: In a Swiss region without universal dental care insurance coverage, prevalence of forgoing dental care for economic reasons was high and highly dependent on income. Efforts should be made to prevent high-risk populations from forgoing dental care.

Contribution of multimorbidity to overall mortality in the population-based CoLaus study

Introduction : Multimorbidity (MM) is currently a major health concern for hospitalized patients but little is known about the relative importance of MM in the general population. Accordingly we assessed whether MM could be a good predictor of overall mortality. Method : Data from the population based CoLaus Study: 3239 participants (1731 women, mean age 50+/-9 years) followed for a median time of 5.4 years (range 0.4 to 8.5 years). MM was defined as presenting >=2 morbidities according to Barnett et al. (27 items, measured data). Survival analysis was conducted using Cox regression. Results : During follow-up, 53 (1.6%) participants died. Participants who died had a higher number of morbidities (2.4 +/- 1.6 vs. 1.9 +/- 1.5, p<0.05) and had a higher prevalence of MM (69.8% vs. 55.9%, p<0.05). On bivariate analysis, presence of MM (defined as a yes/no variable) was significantly related with overall mortality: relative risk (RR) of 1.84, 95% confidence interval [1.02; 3.31], p<0.05 (see figure), but this association became non-significant after adjusting for age, gender and smoking: RR=1.68 [0.93; 3.04], p=0.09. Similar results were obtained when using the number of morbidities: RR for an extra morbidity 1.22 [1.05; 1.44], p<0.02; after adjusting for age, gender and smoking, RR=1.16 [0.99; 1.37], p=0.07. Conclusion : During a short 5 year observation period, measured MM in the general population is associated with overall mortality. This association becomes borderline significant after multivariate adjustment. These observations will have to be confirmed during a longer follow-up period. This increased mortality in MM patients may require developing specific strategies of screening and prevention.

Age-related changes in the bimanual advantage and in brain oscillatory activity during tapping movements suggest a decline in processing sensory reafference

Deficits in the processing of sensory reafferences have been suggested as accounting for age-related decline in motor coordination. Whether sensory reafferences are accurately processed can be assessed based on the bimanual advantage in tapping: because of tapping with an additional hand increases kinesthetic reafferences, bimanual tapping is characterized by a reduced inter-tap interval variability than unimanual tapping. A suppression of the bimanual advantage would thus indicate a deficit in sensory reafference. We tested whether elderly indeed show a reduced bimanual advantage by measuring unimanual (UM) and bimanual (BM) self-paced tapping performance in groups of young (n = 29) and old (n = 27) healthy adults. Electroencephalogram was recorded to assess the underlying patterns of oscillatory activity, a neurophysiological mechanism advanced to support the integration of sensory reafferences. Behaviorally, there was a significant interaction between the factors tapping condition and age group at the level of the inter-tap interval variability, driven by a lower variability in BM than UM tapping in the young, but not in the elderly group. This result indicates that in self-paced tapping, the bimanual advantage is absent in elderly. Electrophysiological results revealed an interaction between tapping condition and age group on low beta band (14âeuro"20 Hz) activity. Beta activity varied depending on the tapping condition in the elderly but not in the young group. Source estimations localized this effect within left superior parietal and left occipital areas. We interpret our results in terms of engagement of different mechanisms in the elderly depending on the tapping mode: a âeuro~kinestheticâeuro? mechanism for UM and a âeuro~visual imageryâeuro? mechanism for BM tapping movement.

Opportunity for sexual selection and effective population size in the lek-breeding European treefrog (Hyla arborea).

Sexual selection in lek-breeding species might drastically lower male effective population size, with potentially important consequences for evolutionary and conservation biology. Using field-monitoring and parental-assignment methods, we analyzed sex-specific variances in breeding success in a population of European treefrogs, to (1) help understanding the dynamics of genetic variance at sex-specific loci, and (2) better quantify the risk posed by genetic drift in this species locally endangered by habitat fragmentation. The variance in male mating success turned out to be markedly lower than values obtained from other amphibian species with polygamous mating systems. The ratio of effective breeding size to census breeding size was only slightly lower in males (0.44) than in females (0.57), in line with the patterns of genetic diversity previously reported from H. arborea sex chromosomes. Combining our results with data on age at maturity and adult survival, we show that the negative effect of the mating system is furthermore compensated by the effect of delayed maturity, so that the estimated instantaneous effective size broadly corresponded to census breeding size. We conclude that the lek-breeding system of treefrogs impacts only weakly the patterns of genetic diversity on sex-linked genes and the ability of natural populations to resist genetic drift.

La pratique infirmière avancée [Advanced practice nursing].

Dans les sociétés contemporaines axées sur le savoir, plus grande sera la proportion de leur population détentrice d'une formation supérieure et engagée en recherche, plus avancé sera leur développement économique et social.1,2 Par contre, dans ces sociétés, le vieillissement de la population, l'importance ccordée aux soins de santé axés sur les maladies chroniques et les coûts financiers de ceux-ci exercent une forte pression sur les systèmes de santé. Les nterventions doivent donc être les plus efficaces possible, avec un rapport coût/efficacité optimal. Cela requiert que les infirmières soient capables d'oeuvrer en pratique avancée, c'est-à-dire capables de développer, implémenter et évaluer des approches cliniques infirmières basées sur des preuves, de tester de nouvelles interventions potentiellement plus efficientes et de promouvoir un programme de recherche portant explicitement sur l'amélioration de la qualité et sécurité des soins en contexte d'interdisciplinarité.

A set of indicators for decomposing the secular increase of life expectancy.

ABSTRACT: BACKGROUND: The ongoing increase in life expectancy in developed countries is associated with changes in the shape of the survival curve. These changes can be characterized by two main, distinct components: (i) the decline in premature mortality, i.e., the concentration of deaths around some high value of the mean age at death, also termed rectangularization of the survival curve; and (ii) the increase of this mean age at death, i.e., longevity, which directly reflects the reduction of mortality at advanced ages. Several recent observations suggest that both mechanisms are simultaneously taking place. METHODS: We propose a set of indicators aiming to quantify, disentangle, and compare the respective contribution of rectangularization and longevity increase to the secular increase of life expectancy. These indicators, based on a nonparametric approach, are easy to implement. RESULTS: We illustrate the method with the evolution of the Swiss mortality data between 1876 and 2006. Using our approach, we are able to say that the increase in longevity and rectangularization explain each about 50% of the secular increase of life expectancy. CONCLUSION: Our method may provide a useful tool to assess whether the contribution of rectangularization to the secular increase of life expectancy will remain around 50% or whether it will be increasing in the next few years, and thus whether concentration of mortality will eventually take place against some ultimate biological limit.

Compliance with the Swiss Society for Nutrition's dietary recommendations in the population of Geneva, Switzerland: a 10-year trend study (1999-2009).

The trends in compliance with the dietary recommendations of the Swiss Society for Nutrition in the Geneva population were assessed for the period from 1999 to 2009 using 10 cross-sectional, population-based surveys (Bus Santé study) with a total of 9,320 participants aged 35 to 75 years (50% women). Dietary intake was assessed using a self-administered, validated, semi-quantitative food frequency questionnaire. Trends were assessed by logistic regression adjusting for age, smoking status, education, and nationality using survey year as the independent variable. After excluding participants with extreme intakes, the percentage of participants with a cholesterol intake of <300 mg/day increased from 40.8% in 1999 to 43.6% in 2009 for men (multivariate-adjusted P for trend=0.04) and from 57.8% to 61.4% in women (multivariate-adjusted P for trend=0.06). Calcium intake >1 g/day decreased from 53.3% to 46% in men and from 47.6% to 40.7% in women (multivariate-adjusted P for trend<0.001). Adequate iron intake decreased from 68.3% to 65.3% in men and from 13.3% to 8.4% in women (multivariate-adjusted P for trend<0.001). Conversely, no significant changes were observed for carbohydrates, protein, total fat (including saturated, monounsaturated, and polyunsaturated fatty acids), fiber, and vitamins D and A. We conclude that the quality of the Swiss diet did not improve between 1999 and 2009 and that intakes deviate substantially from expert recommendations for health promotion and chronic disease risk reduction.

Gait and foot clearance parameters obtained using shoe-worn inertial sensors in a large-population sample of older adults

In order to distinguish dysfunctional gait; clinicians require a measure of reference gait parameters for each population. This study provided normative values for widely used parameters in more than 1400 able-bodied adults over the age of 65. We also measured the foot clearance parameters (i.e., height of the foot above ground during swing phase) that are crucial to understand the complex relationship between gait and falls as well as obstacle negotiation strategies. We used a shoe-worn inertial sensor on each foot and previously validated algorithms to extract the gait parameters during 20 m walking trials in a corridor at a self-selected pace. We investigated the difference of the gait parameters between male and female participants by considering the effect of age and height factors. Besides; we examined the inter-relation of the clearance parameters with the gait speed. The sample size and breadth of gait parameters provided in this study offer a unique reference resource for the researchers.