Efficacy of immunotherapy in mismatch repair-deficient advanced colorectal cancer in routine clinical practice. An AGEO study.

BACKGROUND: Immunotherapy demonstrated remarkable efficacy in metastatic colorectal cancers (mCRCs) with mismatch repair deficiency (MMRd)/microsatellite instability (MSI). However, data regarding efficacy and safety of immunotherapy in the routine clinical practice are scarce. PATIENTS AND METHODS: This is a retrospective, multicenter study aiming to evaluate efficacy and safety of immunotherapy in routine clinical practice and to identify predictive markers for long-term benefit. Long-term benefit was defined as progression-free survival (PFS) exceeding 24 months. All patients who received immunotherapy for an MMRd/MSI mCRC were included. Patients who received immunotherapy in combination with another known effective therapeutic class agent (chemotherapy or tailored therapy) were excluded. RESULTS: Overall, 284 patients across 19 tertiary cancer centers were included. After a median follow-up of 26.8 months, the median overall survival (mOS) was 65.4 months [95% confidence interval (CI) 53.8 months-not reached (NR)] and the median PFS (mPFS) was 37.9 months (95% CI 30.9 months-NR). There was no difference in terms of efficacy or toxicity between patients treated in the real-world or as part of a clinical trial. Overall, 46.6% of patients had long-term benefit. Independent markers associated with long-term benefit were Eastern Cooperative Oncology Group-performance status (ECOG-PS) 0 (P = 0.025) and absence of peritoneal metastases (P = 0.009). CONCLUSIONS: Our study confirms the efficacy and safety of immunotherapy in patients with advanced MMRd/MSI CRC in the routine clinical practice. ECOG-PS score and absence of peritoneal metastases provide simple markers that could help identify patients who benefit the most from this treatment.

Food groups associated with a reduced risk of 15-year all-cause death.

BACKGROUND/OBJECTIVES: Long-term observational cohorts provide the opportunity to investigate the potential impact of dietary patterns on death. We aimed to investigate all-cause death according to the consumption of selected food groups, and then to identify those independently associated with reduced mortality. SUBJECTS/METHODS: Population survey of middle-aged men randomly selected in the period 1995-1997 from the general population of three French areas and followed over a median of 14.8 years. Dietary data were collected through a 3-day food record. Cox modeling was used to assess the risk of death according to selected foods groups after extensive adjustment for confounders, including a diet quality index. RESULTS: The study population comprised 960 men (mean age 55.5 ±6.2 years). After a median follow-up of 14.8 (interquartile range 14.3-15.2) years, 150 (15.6%) subjects had died. Food groups that remained independently predictive of a lower risk of death after extensive adjustment were an above-median consumption of milk (adjusted relative risk: 0.61, 95% confidence interval (CI): 0.43-0.86, P-value=0.005), fruits and vegetables (0.68, 0.46-0.98, P-value=0.041) and a moderate consumption of yogurts and cottage cheese (0.50, 95% CI: 0.31-0.81, P-value=0.005), other cheeses (0.62, 0.39-0.97, P-value=0.036) and bread (0.57, 0.37-0.89, P-value=0.014). Besides, there was a nonsignificant trend for a higher risk of death associated with highest sodium intakes. CONCLUSIONS: Consumption of food groups that largely match recommendations is associated with a reduced risk of all-cause death in men. A diet providing moderate amounts of diverse food groups appears associated with the highest life expectancy.

Pulse wave velocity, pulse pressure and number of carotid or femoral plaques improve prediction of cardiovascular death in a population at low risk.

The assessment of cardiovascular risk is uniformly recommended as a decision-support for therapies aimed at preventing cardiovascular diseases. Our objective was to determine the prognostic significance of vascular markers in apparently healthy subjects. Analyses were based on the Third Toulouse MONICA Survey (1995-1997) carried out in participants aged 35-64, from the general population of South-western France. Causes of death were obtained 14 years after inclusion. There were 1132 participants (51% men). Over the 14-year follow-up period, 61 deaths were recorded, 20% due to a cardiovascular cause. Adding pulse wave velocity (PWV) to Framingham Risk Score (FRS) improved the accuracy of the risk prediction model. The C-statistic increased from 0.76 (95% confidence interval (CI): 0.64-0.89) (FRS alone) to 0.79 (95% CI: 0.64-0.95) (FRS+PWV). The Integrated Discrimination Improvement (IDI) reached 3.81% (P-value<0.001) and the net reclassification improvement (NRI) was equal to 32%. Risk prediction was also improved by integrating pulse pressure (PP) in the model (C-statistic=0.81 (95% CI: 0.66-0.96); IDI=4.99% (P-value<0.001); NRI=30%) or the number of carotid or femoral atherosclerotic plaques (C-statistic=0.78 (95% CI: 0.63-0.93); IDI=2.21% (P-value<0.001); NRI=21%). Vascular markers are independent determinants of cardiovascular mortality in apparently healthy subjects and improve risk prediction.

Alcohol consumption patterns and body weight.

BACKGROUND/AIMS: The impact of alcohol on health depends on both the total amount ingested per week and the drinking pattern. Our goal was to assess the relationship between drinking occasions and anthropometric indicators of adiposity. METHODS: For this cross-sectional study, 7,855 men aged 50-59 years were recruited between 1991 and 1993 in France. Clinical and anthropometric data were obtained in a standardized clinical examination by trained staff. Alcohol intake was assessed by a questionnaire recording daily consumption of each type of alcohol during a typical week. RESULTS: 75% of the participants drank alcohol daily (264.7 ml per week). For a given total alcohol intake and after adjustment of confounders, the number of drinking episodes was inversely correlated with body mass index (p < 0.0001) and waist circumference (p < 0.0001). The odds ratio (95% confidence interval) for obesity was 1.8 (1.3-2.4) for occasional (1-2 days/week) and 1.6 (1.2-2.1) for frequent drinkers (3-5 days/week) compared with daily drinkers. This correlation was less pronounced in moderate (<140 ml/week) than intermediate consumers (140-280 ml/week). In heavy consumers (>280 ml/week), the intake was almost always daily. The results were similar for wine and beer consumption. CONCLUSION: Our findings suggest that drinking occasion is a risk indicator of obesity independent of total alcohol intake.

Evaluation of oral health related to body mass index.

OBJECTIVE: Poor oral health has previously been related to high body mass index (BMI). We aimed at exploring the link between BMI and several oral health markers, after adjustment for dietary patterns and plasma insulin, both of which could act as mediators. SUBJECTS AND METHODS: Dental examination was performed in a sample of 186 French subjects aged 35-64 years and selected from the general population to assess number of missing teeth, periodontitis, clinical attachment loss (CAL), probing pocket depth (PD), gingival index (GI) and plaque index (PI). Data collection also included a food-frequency questionnaire. BMI (considered as outcome variable) was categorized into quartiles, and as BMI<25; 25 ≤BMI<30; and BMI ≥ 30 kg m(-2) . RESULTS: After adjustment for age, gender, education level, smoking, physical activity, energy intake and C-reactive protein, BMI was statistically associated with missing teeth, PD and PI, but not with CAL, GI or periodontitis. After additional adjustment for 'high-carbohydrate' diet and plasma insulin or HOMA (homeostasis model assessment) index for insulin resistance, the statistical relationship between BMI and oral variables remained significant only for PD and PI. CONCLUSIONS: Plaque index, reflecting dental plaque, and PD, closely linked with periodontal inflammation and infection, are statistically associated with high BMI and obesity, independently of dietary patterns and insulin resistance.

[Assessment and characteristics of chronic renal insufficiency in France]. / Estimation et caractérisation de l'insuffisance rénale chronique en France.

Chronic kidney disease (CKD) is a major public health issue. In France, few studies have evaluated CKD prevalence. The objective of the MONA LISA study was to estimate and to characterize CKD in three representative cross-sectional surveys in subjects aged 35-74.9 years. CKD was defined as subjects having MDRD glomerular filtration rate lower than 60 mL/min/1.73 m(2). Prevalence of CKD in MONA LISA was standardized according to the French population. A multiple logistic regression analysis was performed in order to find independent factors associated to CKD. The French estimate of CKD prevalence was 8.2% (95% confidence interval: 7.4-8.9%), that is 2,454,548 (95% confidence interval: 2,215,080-2,664,082) subjects aged 35-74.9 years. Factors significantly and independently associated to CKD were older age, hypertension and dyslipidemias. In conclusion, the MONA LISA study evaluated for the first time in France CKD prevalence in subjects aged 35-74.9 years. This prevalence probably underestimates the real CKD size due to selection bias present in every representative cross-sectional survey.

Cancer mortality according to lipid-lowering drugs and lipoproteins in a general population.

OBJECTIVE: The beneficial effect of lipid-lowering drugs (LLD) on cardiovascular risk is established, but long term safety data remain scarce. Our aim was to assess 10-year risk of cancer mortality according to blood lipoprotein levels and LLD exposure, in a general population. METHODS: Our analysis was based on the Third French MONICA survey on cardiovascular risk factors (1994-1997). Participants were randomly recruited from the general population of three French areas and were aged 35-64 years. Subjects with a history of cancer at baseline were excluded from the analysis. Vital status and cause of mortality were obtained 10 years after inclusion. RESULTS: There were 3262 participants and 177 deaths were recorded over the 10-year period (78 due to a cancer). The sample comprised 64% of normolipidaemic, 25% of untreated dyslipidaemic and 11% of dyslipidaemic subjects treated with LLD (4% statins, 6% fibrates and 1% other hypolipidaemic drugs). After adjustment for centre, age, gender, smoking, gamma-glutamyl transpeptidase and mean corpuscular volume, the hazard ratios (HR) for cancer mortality in subjects with non-HDL cholesterol <3.5 mmol/L (135 mg/dL) and in those with HDL cholesterol <0.90 mmol/L (35 mg/dL) were 2.74 (95% confidence interval: 1.66-4.52, p < 0.001) and 2.83 (1.62-4.96, p < 0.001), respectively. The adjusted HR for cancer mortality was 0.31 (0.11-0.86, p = 0.025) in people on LLD compared to untreated subjects. CONCLUSIONS: In the present study, we confirm the significant association between low cholesterol and cancer mortality without finding any harmful signal regarding cancer risk associated with the use of LLD. The main limitations are remaining baseline differences between treated and untreated subjects (due to the observational design but minimized by the use of extensive adjustments and propensity score methods), and the lack of re-assessment of LLD exposure and cholesterol levels during follow-up, possibly leading to a misclassification bias.

Regional factors interact with educational and income tax levels to influence food intake in France.

BACKGROUND/OBJECTIVES: The goal of the present study was to assess whether geographic factors affect the relationship between socioeconomic indicators and adherence to the French National Nutritional Health Programme (Programme National Nutrition Santé (PNNS)) guidelines. SUBJECTS/METHODS: The MONA LISA-NUT study (2005-2007) is a cross-sectional survey of a representative sample from northern, northeastern and southwestern France. Educational level and household income tax were recorded by trained interviewers. Food intake was assessed with a 3-day food diary in 3188 subjects aged from 35-64 years. Adherence to the PNNS guidelines was assessed with a validated score (the French score of indicators of the PNNS objective (FSIPO)). Multivariate analyses were adjusted for gender, age, marital status, body mass index, energy intake and medically prescribed diets. RESULTS: The FSIPO score was higher in southwestern France than in the two other regions (P<0.0001). The FSIPO score was correlated with the educational level in northern and northeastern France (P<0.0001) but not in southwestern France (region-education interaction: P<0.001). This interaction was accounted for by fruit and vegetable (P<0.0001), calcium (P=0.03), saturated fatty acid (P<0.0001), and fibre (P=0.0001) components of the FSIPO score. In contrast, the income tax level and the FSIPO score were positively correlated (P<0.0001) to a similar extent in all three regions (region × income tax interaction: P=0.09). CONCLUSIONS: The relationship between educational level and adherence to the national nutritional health guidelines differs from one region of France to another, suggesting that nutrition education programmes should perhaps be adapted on a regional basis. In contrast, guideline adherence is correlated with income tax level independently of geographical factors, suggesting that financial constraints on food choices are uniform across France.

Predictors of infarct artery patency after prehospital thrombolysis: the multicentre, prospective, observational OPTIMAL study.

OBJECTIVE: To identify predictors of early TIMI 3 flow patency of the infarct-related artery after prehospital thrombolysis in patients with ST-segment elevation myocardial infarction (STEMI) using data from a "real-world" population, and to develop a nomogram for triaging patients to emergency angiography. DESIGN: Multicentre, observational, prospective, cohort study. SETTING: 79 Hospitals in France with a prehospital mobile intensive care unit and a coronary care unit with 24 h access to coronary angiography. PATIENTS: 997 Patients with STEMI. INTERVENTIONS: All patients received prehospital thrombolysis within 6 h of symptom onset and angiography was performed within 6 h of thrombolysis. MAIN OUTCOME MEASURES: Coronary patency (TIMI flow). RESULTS: The median age of the population was 59 years and the sample comprised 18% women. After multivariable logistic regression analysis, predictors of TIMI 3 flow in the infarct-related artery were current/previous smoking (odds ratio (OR) = 1.60, 95% confidence interval 1.15 to 2.22), < or =5 leads with ST-segment elevation before thrombolysis (OR = 1.59, 1.12 to 2.25), Killip class I (OR = 1.96, 1.05 to 3.67), chest pain relief (OR = 1.62, 1.17 to 2.25) and ST-segment resolution > or =70% (OR = 1.76, 1.29 to 2.38). A nomogram was developed to assess the probability of TIMI 3 flow, according to smoking status, number of leads with ST elevation before thrombolysis, Killip class, chest pain relief and ST-segment resolution. CONCLUSIONS: This study provides quantitative data for predicting success of prehospital thrombolysis. The nomogram is a simple tool for predicting likelihood of coronary patency, based on clinical and electrocardiographic data. It may help to identify patients who require emergency angiography and rescue percutaneous coronary intervention.

Prognostic value of nocturnal blood pressure and reverse-dipping status on the occurrence of cardiovascular events in hypertensive diabetic patients.

AIM: To assess whether reverse-dipping status is associated with cardiovascular (CV) events such as CV death, myocardial infarction (MI) or stroke in diabetic patients with hypertension. METHODS: A total of 97 diabetic patients underwent their first ambulatory blood pressure monitoring (ABPM 1). "Reverse dippers" were defined as patients with a nighttime systolic and/or diastolic blood pressure (BP) greater than daytime systolic and/or diastolic BP. Other patients were called "others". A second ABPM (ABPM 2) was done after a median delay of 2.6 years. Patients were then followed for a further 2.9-year median period (total median follow-up: 5.5 years). RESULTS: After ABPM 1, CV events occurred in 53% of the reverse dippers (n=15) and in 29% of the others (n=82). Kaplan-Meier curves showed significant differences between the two groups (P=0.003). Mean nighttime systolic BP on ABPM 1 was 148+/-23 mmHg and 142+/-19 mmHg in patients who did and did not experience a CV event, respectively. With Cox analysis adjusted for confounders, a 10 mmHg increase in nighttime systolic BP was associated with a 35% increase in the risk of a CV event (hazard ratio [HR]: 1.35, P=0.003). The HR for a CV event in reverse- versus nonreverse-dipping status was 2.79 (P=0.023). After ABPM 2, the relationship between the reverse-dipping status and occurrence of CV events was no longer evident (P=0.678). Nighttime systolic BP remained predictive of CV events (P=0.001). CONCLUSION: These findings suggest that nighttime systolic BP per se appeared to be a stronger predictor of an excess risk of CV events compared with reverse-dipping status.

Perception of risk of adverse drug reactions by medical students: influence of a 1 year pharmacological course.

AIMS: To investigate how adverse drug reactions (ADRs) to several classes of drugs are perceived by young medical students before and after a 1 year pharmacology course. METHODS: The whole cohort of 92 medical students (63 females and 29 males) was questioned during their third year. A visual analogue scale was used to define a score (ranging from 0 to 10) of perceived risk of ADRs associated with each drug class before and at the end of the pharmacological training period. RESULTS: Before the pharmacology course, hypnotics were ranked as the most dangerous drugs by the medical students, followed by antidepressants and anticoagulants. Contraceptive pills were listed in the last position. After pharmacological training, antidepressants moved into the first position, followed by anticoagulants and hypnotics. When all different drug classes were taken as a whole, the mean (+/-SD) of median scores of the perceived risk were 4.8 (+/-1.3) before and 5.8 (+/-1.5) at the end of the pharmacology course (P < 0.0001). Except for antidiabetics, antihypertensive drugs, tranquillizers, corticosteroids and hypnotics, the perceived risk significantly increased after the pharmacology course for the other drugs. The highest increases were observed for contraceptive pills (+104%, P < 0.01), NSAIDs (+86%, P < 0.01) and aspirin (+56%, P < 0.01). CONCLUSIONS: Pharmacological training allows young medical students to be aware of potentially serious ADRs associated with drugs, in particular with drugs considered relatively safe (such as NSAIDs and aspirin) by nonhealth professionals.

Nutritional intakes of 1072 French free-living men with and without diagnosed cardiovascular risk factors.

OBJECTIVE: To compare the dietary intakes of free-living people with and without previously diagnosed diet-modifiable cardiovascular risk factors (hypertension, hypercholesterolaemia and diabetes). DESIGN: Cross-sectional survey on cardiovascular risk factors including a three-consecutive-day food record. SETTING: Multicentre setting in Lille (northern France), Strasbourg (north-east) and Toulouse (south-west) areas. SUBJECTS: A total of 1072 middle-aged men randomly selected from the general population: group 1 (504 men without previously diagnosed diet-modifiable risk factor), group 2 (377 men with one previously diagnosed diet-modifiable risk factor) and group 3 (191 men with two or three previously diagnosed diet-modifiable risk factors). INTERVENTIONS: None. RESULTS: Total daily energy intake equalled 10731 kJ/day (standard error: 119), 9991 (138) and 9737 (166) in groups 1, 2 and 3, respectively (P<0.0001 for ANOVA comparing the three groups), and daily energy intake without alcohol equalled 9860 (115), 9096 (132) and 8654 (159) kJ/day (P<0.0001). The proportion of calories from animal proteins (in daily energy intake without alcohol) increased from group 1 to 3 (P<0.0001), whereas the proportion from oligosaccharides decreased (P<0.0001). The proportion of calories from alcohol (in total daily energy intake) increased with the number of risk factors (P<0.0001). These results remained significant after adjustment for confounders. No significant group differences were found in the proportions of energy from polysaccharides, saturated, monounsaturated and polyunsaturated fats. CONCLUSIONS: As compared with subjects without risk factor, significant quantitative and qualitative changes are observed in individuals with diagnosed hypertension, hypercholesterolaemia or diabetes. However, lower consumptions of saturated fats and alcohol are needed.

Perception of the risk of gastrointestinal adverse drug reactions with non-steroidal anti-inflammatory drugs (including coxibs): differences among general practitioners, gastroenterologists and rheumatologists.

OBJECTIVE: To compare the perception of risk of gastrointestinal adverse drug reactions (ADRs) with non-steroidal anti-inflammatory drugs (NSAIDs) (including coxibs) in general practitioners, gastroenterologists and rheumatologists. METHODS: Physicians (69 general practitioners, 45 gastroenterologists and 58 rheumatologists; 172 total) were interviewed using visual analogue scales in order to define a score of perceived risk (ranking from 0 to 10) of gastrointestinal ADRs associated with four classes of NSAIDs (indolics, oxicams, arylcarboxylic derivatives, coxibs). RESULTS: When the three groups of physicians were taken as a whole, indolic derivatives were ranked as the most dangerous NSAIDs [median score: 5.3 (25-75th percentiles: 3.5-7)] followed by oxicams [median score: 5.0 (25-75th percentiles: 3.1-6.2)], arylcarboxylic derivatives [median score 4.7 (25-75th percentiles: 3.0-6.5)] and coxibs [median score 1.9 (25-75th percentiles: 1.2-3.0)]. Among physicians, general practitioners gave the most important mean score [median score 4.8 (25-75th percentiles: 3.4-5.7)] for NSAIDs as a whole followed by gastroenterologists [median score 4.6 (25-75th percentiles: 3.6-5.6)] and rheumatologists [median score 3.6 (25-75th percentiles: 2.3-4.7)]. There was no significant difference among the three groups of physicians in the median score of perceived digestive risk associated with the use of indolic derivatives, whereas significant differences were found for arylcarboxylic derivatives, oxicams and coxibs, with higher median scores given by gastroenterologists followed by general practitioners and rheumatologists. CONCLUSION: This study shows differences in the perception of risks of gastrointestinal ADRs. Rheumatologists systematically considered NSAIDs as less harmful than general practitioners and gastroenterologists did. In contrast, the widely demonstrated difference in gastrointestinal risk among the different groups of NSAIDS (with, for example, a higher risk for oxicams) was not pointed out by the three studied groups of physicians. There are differences in the perception of gastrointestinal risks of NSAIDs (including coxibs) among physicians according to their medical education and medical specialisation.

[Prevalence and management of patients with a prior history of atherothrombotic disease in primary care in France. Results of the ECLAT1 survey]. / Prévalence et prise en charge des patients avec antécédents athérothrombotiques dans le cadre des consultations de médecine générale en France. Résultats de l'enquête ECLAT1.

This cross-sectional study assessed the prevalence of subjects with a previous history of atherothrombotic disease (myocardial infarction, ischemic stroke and/or lower limb arterial disease) among patients treated in general medicine. A random sample of 3,009 French general practitioners was recruited. Patients who consulted one of these general practitioners on December 7th 2000 were included. Those with a previous history of atherothrombotic disease were identified and further data on their cardiovascular risk factors and drug use were collected. The prevalence of patients with a previous history of atherothrombotic disease was 2% [95% confidence interval: 1.9-2-1] in subjects younger than 65, 13.4% [12.7-14.2] between 65 and 74 and 17.0% [16.2-17.8] in subjects older than 74. Arterial hypertension was found in 62.2% of the patients with a previous history of atherothrombotic disease, overweight or obesity in 59.4%, hypercholesterolaemia in 55%, current or past smoking in 48.3%, and diabetes mellitus in 20.1%. The last blood pressure and LDL-cholesterol measurements were respectively higher than or equal to 140/90 mmHg and 3 mmol/l in 70.6% of the patients suffering from arterial hypertension (missing data in 2.2%) and in 48.2% of the patients suffering from hypercholesterolaemia (missing data in 31.4%). Atherothrombosis represents a significant part of the primary care activity in France. Despite a widespread antihypertensive and hypocholesterolaemic drug prescription, the control of cardiovascular risk factors is insufficient. The high prevalence of overweight may contribute to this poor control.

Physical activity patterns in 50-59 year men in France and Northern Ireland. Associations with socio-economic status and health behaviour.

BACKGROUND: This study aimed to compare physical activity patterns and their associations with socio-economic status (SES) and health behaviour in two countries at contrasting risk for coronary heart disease (CHD). METHODS: This paper is a cross-sectional analysis of 7359 French and 2398 Northern Irish 50-59 year men of the PRIME cohort. Net energy expenditure due to physical activity (PAE) was assessed by means of the MOSPA-Q taking high-intensity recreational activities into account. SES was evaluated by educational attainment and material conditions. Different behavioural factors (smoking, alcohol intake and healthy eating patterns) were considered. RESULTS: The prevalence of walking or cycling to work was greater in Northern Ireland (p < 10(-5)) whereas leisure PAE (p < 10(-5)) and high-intensity leisure-time activity (p < 10(-5)) were higher in France. Education was positively associated with leisure-time PAE in Northern Ireland but negatively in France. However education in both countries and material conditions in France were favourably associated with the regular practice of high-intensity recreational activities. Alcohol consumption was positively associated with leisure PAE in France only (p < 10(-3)). A weak negative association was also observed between smoking and leisure-time activities while healthy eating patterns were associated with greater physical activity in both countries. CONCLUSIONS: Physical activity patterns and their relationships with SES and alcohol consumption differ in France and in Northern Ireland. Our results underline the need to focus on low socio-economic groups for health promotion but, also, to adapt strategies to promote physical activity according to cultural differences between countries. Our results also show that healthy behaviours tend to cluster in middle-aged men.

Eating frequency and body fatness in middle-aged men.

OBJECTIVE: The relationship between eating frequency and body fatness was tested in a population sample. DESIGN: A cross-sectional survey on cardiovascular risk factors and a nutritional survey were carried out from June 1996 to April 1997. SUBJECTS: Population sample of 330 free-living middle-aged men (45-64 y). MEASUREMENTS: Body mass index (BMI), waist-to-hip ratio (WHR) and nutritional survey (3-day record). RESULTS: In the whole sample, BMI and WHR decreased significantly (P<0.05) along with the increase of the number of eating occasions. When low energy records were excluded, the trend for BMI and WHR according to eating categories remained significant. For WHR, averages were 0.98, 0.95, 0.94 and 0.93 for 1-2, 3, 4 or 5 or more feedings a day, respectively. For BMI, mean values were 28.1, 26.2, 26.2 and 24.5 kg/m(2), respectively. After adjustment for confounders (total energy intake or macronutrients, age, educational level, smoking habits, physical activity and restrained diet), the linear trend for BMI and WHR throughout feeding categories was significant when the whole sample was considered. This relationship remained similar when low energy records or when dieters were excluded. CONCLUSION: These results suggest that for an isoenergetic intake the increase of eating frequency is associated with lower body fatness.

Perception of the risk of adverse drug reactions: differences between health professionals and non health professionals.

AIMS: To investigate how risk of adverse drug reactions (ADRs) of several drug classes is perceived by health vs non health professionals. METHODS: Four hundred health professionals (i.e. 278 general practitioners, 76 pharmacists and 46 pharmacovigilance professionals) and 153 non health professionals were interviewed. Visual analogue scales were used to define a score of perceived risk of ADRs associated with each drug class (ranking from 0 to 10). RESULTS: Anticoagulants were ranked as the most dangerous drugs by general practitioners [median score (25th-75th centiles): 7.9 (6.7-9.0)], pharmacists [8.7 (7.8-9.7)] and pharmacovigilance professionals [8.1 (7.2-9.0)]. For non health professionals, the class ranked first was sleeping pills [8.7 (7.2-9.4)] followed by tranquillisers [8.2 (6.4-9.2)] and antidepressants [8.0 (5.9-9.1)]. Aspirin was listed in the last position by non health professionals [3.4 (1.5-5.4)]. CONCLUSIONS: There are major differences in the perception of risk of ADRs between health professionals and non health professionals.