Low Back Pain and Upper-Extremity Musculoskeletal Disorders in French Postal Workers Driving Light-Duty Vehicles for Mail and Parcel Delivery.

Occupational driving of light-duty vehicles (LDVs) became increasingly important in parcel delivery faced with the explosive growth of e-commerce. Since musculoskeletal disorders (MSDs) represent the most reported driving-related health problem, we aimed to analyze the risk of low back pain (LBP) and upper-extremity musculoskeletal disorders (UEMSDs) associated with driving LDVs for parcel delivery. In 306 postal workers exposed to driving and 100 unexposed workers, information on occupational driving, physical/psychosocial constraints, and work organization were collected via a questionnaire. MSDs were assessed using the Nordic Questionnaire, 14 additional questions regarding LBP, and a standardized clinical examination for UEMSDs. Statistical modeling consisted of multivariable logistic regression for UEMSDs and the item response theory approach for LBP. UEMSDs were associated with the distance of rural rounds and inversely associated with urban/mixed delivery rounds. Handling heavy loads was associated with LBP, and high physical demands during delivery rounds were related to MSDs. Karasek dimensions and mobbing actions were associated with MSDs. Work recognition, driving training, using an automatic gearbox, and the utilization of additional staff during peak periods were inversely associated with MSDs. Our results suggest that the distance driven in rural settings and high physical demands were associated with MSDs, while some organizational factors could protect from MSDs.

Risks for adverse pregnancy outcomes and infections in daycare workers: an overview of current epidemiological evidence and implications for primary prevention.

Childcare providers are overwhelmingly women of childbearing age. Occupational risks in this sector include exposure to biological (infectious) or physical (standing, carrying loads) hazards, many of which are associated with adverse pregnancy outcomes such as children with congenital infections, low birth weight or prematurity. Here, the authors examined literature on pregnancy outcomes and infectious hazards related to employment in daycare settings. Overall, 33 original studies (10 reporting pregnancy issues, 23 focusing on infectious risks) published in 1980-2018 were retained following a Medline search. Pregnancy issues in daycare workers have rarely been studied, and inconsistent risks of spontaneous abortion, congenital malformations and fetal growth retardation have been reported. Literature pertaining to infectious risks in daycare settings is extensive. The risk of a primary cytomegalovirus infection during pregnancy was increased for daycare workers caring for >6 children and younger children, changing diapers ≥3 days/week, not wearing gloves when changing diapers, and having employment in daycare for ≤2 years. Personal factors (nulliparity, ethnicity) were also independent risk factors. Parvovirus B19 (B19V) infections appear to be related to employment in daycare, but also to having one's own children and an increased number of siblings. Consequently, the risk of a primary B19V infection during an outbreak is of most concern among younger nulliparous workers caring for large numbers of young infected children. Since the main occupational hazard is viral infection, feasible prevention strategies include improving workers' awareness, serological monitoring during pregnancy, educating on appropriate preventive measures, and ensuring age-appropriate immunization of children and staff in childcare facilities. Int J Occup Med Environ Health. 2020;33(6):733-56.

Qualitative and Semiquantitative Assessment of Exposure to Engineered Nanomaterials within the French EpiNano Program: Inter- and Intramethod Reliability Study.

The relatively recent development of industries working with nanomaterials has created challenges for exposure assessment. In this article, we propose a relatively simple approach to assessing nanomaterial exposures for the purposes of epidemiological studies of workers in these industries. This method consists of an onsite industrial hygiene visit of facilities carried out individually and a description of workstations where nano-objects and their agglomerates and aggregates (NOAA) are present using a standardized tool, the Onsite technical logbook. To assess its reliability, we implemented this approach for assessing exposure to NOAA in workplaces at seven workstations which synthesize and functionalize carbon nanotubes. The prediction of exposure to NOAA using this method exhibited substantial agreement with that of the reference method, the latter being based on an onsite group visit, an expert's report and exposure measurements (Cohen kappa = 0.70, sensitivity = 0.88, specificity = 0.92). Intramethod comparison of results for exposure prediction showed moderate agreement between the three evaluators (two program team evaluators and one external evaluator) (weighted Fleiss kappa = 0.60, P = 0.003). Interevaluator reliability of the semiquantitative exposure characterization results was excellent between the two evaluators from the program team (Spearman rho = 0.93, P = 0.03) and fair when these two evaluators' results were compared with the external evaluator's results. The project was undertaken within the framework of the French epidemiological surveillance program EpiNano. This study allowed a first reliability assessment of the EpiNano method. However, to further validate this method a comparison with robust quantitative exposure measurement data is necessary.

Effects of occupational exposure to poorly soluble forms of beryllium on biomarkers of pulmonary response in exhaled breath of workers in machining industries.

OBJECTIVE: To analyze the effects of occupational exposure to poorly soluble forms of beryllium (Be) on biomarkers of pulmonary inflammation using exhaled breath condensate (EBC) in workers employed in machining industries. METHODS: Twenty machining operators were compared to 16 controls. The individual exposure to Be was assessed from the work history with several indices of exposure calculated on the basis of task-exposures matrices developed for each plant using historical air measurements. Clinical evaluation consisted in a medical questionnaire, measurements of biomarkers in EBC (tumor necrosis factor alpha (TNF-α), total nitrogen oxides (NOx)), measurement of the fraction of exhaled nitric oxide (FeNO) and resting spirometry. Adjusted multiple linear regressions were used to study the effect of the exposure to Be on inflammatory biomarkers. RESULTS: Levels of TNF-α and NOx in EBC were not statistically different between exposed and controls. We found a statistically significant relationship between levels of TNF-α in EBC and both index of cumulative exposure and duration of exposure to Be. No other statistically significant relationships were found between exposure to Be and pulmonary response. CONCLUSION: Our results suggest that machining-related exposure to Be is related to pulmonary inflammation involving TNF-α. These findings must be confirmed by larger studies.

Beryllium in exhaled breath condensate as a biomarker of occupational exposure in a primary aluminum production plant.

OBJECTIVE: Low beryllium exposure can induce pulmonary granulomatosis, so called berylliosis. For occupational health monitoring, it is more relevant to assess the internal dose of Be received by the lungs than urinary or atmospheric Be. Exhaled breath condensate (EBC) is a matrix collected non-invasively that derives from the airway lining fluid. EBC beryllium (Be) levels were evaluated as a marker of occupational exposure in a primary aluminum production plant. METHODS: We collected urine and EBC from controls and workers recently exposed to beryllium in the pot room and the anode repair sectors, and calculated a cumulative beryllium exposure index (CBEI) summing the number of years of employment in each task and multiplying by the estimated average beryllium exposure for the task. Concentrations of beryllium and aluminum were measured in EBC (Be-EBC and Al-EBC) and in urine (Be-U and Al-U) by ICP-MS. RESULTS AND CONCLUSION: We have shown that it was possible to measure Be and Al in workers' EBC. Compared with controls and after adjustment for smoking status, levels of Be-EBC and Al-EBC were higher in pot room workers and exposed subjects, respectively. Due to its relationship with CBEI, but not with Be-U, it appears that Be-EBC could be a promising marker of occupational exposure and provide additional toxicokinetic information in occupational health studies.

Reproductive disorders in hairdressers and cosmetologists: a meta-analytical approach.

OBJECTIVES: The aim of this study was to perform a systematic review and to use a meta-analytical approach to assess quantitatively the risk of adverse pregnancy outcomes in hairdressers and cosmetologists. METHODS: A systematic literature search up to 1 February 2012 was carried out using major bibliographic databases, grey literature, contacts with research teams working on the subject, review papers and reference lists of selected articles. Observational studies reporting measures of effects in relation with body care (hairdressers, cosmetologists, etc.) and reproductive disorders were included. Study quality was assessed by three reviewers. The estimated risk ratios (RR) from all studies reporting on identical outcomes were combined using an average of logarithm transformation of estimated RR weighted by their inverted variance. Statistical heterogeneity across studies was assessed using Cochran's Q test. To explore the sources of heterogeneity, several sensitivity analyses and subgroup analyses were conducted based on study quality, country, study period, alcohol consumption, smoking habit, jobs and control populations. RESULTS: Nineteen studies were selected and reviewed in-depth. The combined risk ratios (RRcs) of five reproductive outcomes were calculated and found to be significantly increased for four outcomes: time to pregnancy, which had an RRc of 1.11 (95% CI: 1.03-1.19); premature birth, which had an RRc of 1.05 (95% CI: 0.99-1.11); small for gestational age, which had an RRc of 1.24 (95 CI%: 1.10-1.41); low birth weight, which had an RRc of 1.21 (95% CI: 1.06-1.39); and embryonic and fetal losses, which had an RRc of 1.19 (95% CI: 1.03-1.38). CONCLUSIONS: This work confirms a weak increase in risk of some reproductive disorders in female hairdressers/cosmetologists. However, the evidence level is rather weak, and a causal association between job and reproductive outcomes cannot be asserted.

Development of a French epidemiological surveillance system of workers producing or handling engineered nanomaterials in the workplace.

OBJECTIVE: Concern has been raised about the potential impact of nanomaterials exposure on human health, and France has decided to implement a timely epidemiological surveillance tool of workers likely to be exposed to engineered nanomaterials that could accompany the development of nanotechnologies. METHODS: A comprehensive review of the toxicological and epidemiological literature has been conducted together with an exploratory study among French companies producing or handling nanoobjects. RESULTS: A double surveillance system is proposed consisting of a prospective cohort survey and repeated cross-sectional studies. The aim of the cohort is (1) to monitor long-term health effects and (2) to allow of further research. Setting-up an exposure registry is the first planned step. CONCLUSIONS: The protocol is about to be submitted to the French Government for approval and funding.

The prognostic value of circulating markers of collagen turnover after acute myocardial infarction.

BACKGROUND: We assessed the time profiles and prognostic utility of circulating markers of collagen turnover (CTO) following acute myocardial infarction (MI). In contrast to previous studies, no patient had been pre-treated with inhibitors of the renin-angiotensin-aldosterone system (RAAS) at the time of initial assessment. METHODS: Plasma levels of N-terminal fragment of type I collagen (PINP), carboxy-terminal telopeptide of type I collagen (ICTP), N-terminal fragment of type III collagen (PIIINP), matrix metalloproteinase-1(MMP-1) and tissue inhibitor of MMPs type-1 (TIMP-1) were assessed in 233 patients following acute MI. The CTO markers were initially assessed prior to treatment by either captopril or losartan, at a median of 3 days following MI. In addition, blood samples were acquired at 1 month, 1 year and 2 years following MI. Development of heart failure symptoms, all-cause and cardiovascular death were recorded as endpoints during two years of follow-up. RESULTS: With the exception of PIIINP, all CTO markers demonstrated significant longitudinal changes following MI. At baseline, ICTP (p<0.0001) and TIMP-1 (p=0.01) levels were significantly elevated in patients who later died compared with survivors. In multivariable analysis only ICTP reached statistical significance as predictor of all cause death (p=0.048). In patients developing symptoms of heart failure during follow-up, ICTP was the only significantly elevated CTO marker (p<0.01). CONCLUSION: The present study supports a prognostic role for ICTP in both the acute and chronic phase following MI.

Extracellular matrix turnover and inflammatory markers independently predict functional status and outcome in chronic heart failure.

BACKGROUND: Inflammatory pathways may promote extracellular matrix (ECM) remodeling and chronic heart failure (CHF) progression. The relationship between markers of inflammation and of ECM remodeling, and their influence on functional status and outcomes has not been examined in a large cohort of CHF patients. METHODS AND RESULTS: We measured baseline blood serum collagen (amino-terminal propeptide of collagen III [PIIINP], metalloproteinase 1 [MMP-1], tissue inhibitor of metalloproteinase 1 [TIMP-1]), and inflammatory (high-sensitivity C-reactive protein [(hsCRP], interleukin [IL]-18, IL-10) markers in 1009 patients enrolled in the Research into Etanercept Cytokine Antagonism in Ventricular Dysfunction (RECOVER) trial. A positive correlation was detected between the 2 classes of markers (PIIINP to IL-18, MMP-1 and TIMP-1 to CRP, TIMP-1 to IL-18, MMP-1 to IL-10). In the adjusted multivariable model including all biomarkers, only PIIINP (P = .03) and MMP-1 (P = .048) were independent predictors of 6-minute walk test (6-MWT), whereas in another model including only inflammatory biomarkers, IL-18 was an independent predictor. PIIINP (P = .001) was the only biomarker independently associated with death and CHF hospitalization. CONCLUSIONS: The independent associations of PIIINP and MMP-1 with 6-MWT and PIIINP with CHF morbi-mortality suggest that excessive ECM turnover may be associated with functional capacity deterioration and poor outcome.

Effects of valsartan alone versus valsartan/simvastatin combination on ambulatory blood pressure, C-reactive protein, lipoproteins, and monocyte chemoattractant protein-1 in patients with hyperlipidemia and hypertension.

Angiotensin receptor blockers have been hypothesized to have synergistic effects with statins. We evaluated the effects of valsartan alone or combined with simvastatin on blood pressure (BP) and indexes of inflammation and oxidant stress in hypertensive patients with hyperlipidemia. In this double-blind trial, 404 patients were randomized to 12 weeks valsartan 160 mg (V) or valsartan 160 mg plus simvastatin 20 mg (V/S20) or 80 mg (V/S80). Twenty-four-hour mean ambulatory BP and biochemical marker measurements were recorded at baseline and study end. There were no statistically significant between-treatment differences for least-square mean reductions from baseline in systolic BP (V, -9.22; V/S20, -9.25; V/S80, -9.58 mm Hg; p <0.0001 for all within-treatment changes vs baseline). Plasma high-sensitivity C-reactive protein decreased with the combinations but not with V alone (least-square mean median change from baseline, -0.16, -0.20, -0.70 mg/L; p = 0.0001 for V/S80 vs baseline; p = 0.045 for V/S20 vs baseline; p = 0.0023 for V/S80 vs V/S20; p = 0.0045 for V/S80 vs V). Monocyte chemoattractant protein-1 was reduced by V, with no evidence for additional lowering with V/S combinations. In conclusion, addition of simvastatin to valsartan did not incrementally lower BP. However, V/S80 was superior to V and V/S20 in reducing high-sensitivity C-reactive protein.

Serum BNP, hs-C-reactive protein, procollagen to assess the risk of ventricular tachycardia in ICD recipients after myocardial infarction.

AIMS: Ventricular arrhythmia is the main cause of sudden cardiac death. Intracardiac strain, myocardial and extracellular matrix remodelling, and subsequent myocardial fibrosis are involved in arrhythmia pathogenesis. The present study investigates the relationship between cardiac fibrosis [procollagen type I aminoterminal peptide (PINP), procollagen type III aminoterminal peptide (PIIINP), TIMP1, membrane metalloproteinase I], pressure overload [brain natriuretic peptide (BNP)] inflammation [high sensitivity (hs)-C-reactive protein] serum markers, and the incidence of ventricular tachycardia (VT) in implantable cardioverter-defibrillators (ICD) recipients. METHODS AND RESULTS: Serum markers were collected in 121 patients implanted for spontaneous sustained VT and a prior history of myocardial infarction. VT incidence was obtained during ICD interrogation. Over a 1 year period, 38 patients (31%) experienced at least 1 VT. In a multivariate analysis, a left ventricular ejection fraction <0.35 (OR = 2.19, 95%CI 1.00-4.79, P = 0.049), an increased serum BNP (OR = 3.75, 95%CI 1.46-9.67, P = 0.014), an increased hs-C-reactive protein (OR = 3.2, 95%CI 1.26-8.10, P = 0.006), an increased PINP (OR = 3.71, 95%CI 1.40-9.88, P = 0.009), and a decreased PIIINP (OR = 0.21, 95%CI 0.08-0.59, P = 0.003) were associated with a higher VT incidence. CONCLUSION: In coronary artery disease patients: (1) BNP is not only a marker of left ventricular dysfunction, but also a marker of VT; (2) combined 'high PINP and low PIIINP' is a strong VT marker; and 3) inflammatory process is involved in VT pathogenesis.

Residual stress ischaemia is associated with blood markers of myocardial structural remodelling.

BACKGROUND: Long-term prognosis of coronary artery disease (CAD) patients is worsened when stress ischemia persists on treatment, but the relationship with adverse cardiac remodelling had never been investigated. AIM: To analyze changes in blood markers of fibrosis in patients with chronic CAD exhibiting exercise ischaemia. METHODS: Circulating markers of collagen: (i) turnover (amino-terminal propeptide of collagen-III [PIIINP]) and (ii) degradation (matrix metalloproteinase 1 [MMP-1]), were obtained in 139 CAD patients referred for exercise 201Tl-SPECT. RESULTS: In the 57 patients who had SPECT-ischaemia, PIIINP was higher (4.3+/-2.9 microg L-1 vs. 3.1+/-1.5 microg L-1, p=0.002) and MMP-1 lower (3.8+/-2.1 microg L-1 vs. 4.7+/-2.8 microg L-1, p=0.04) than in the 82 patients without SPECT-ischaemia. PIIINP was independently related to LV volume, SPECT-ischaemia and age, whereas MMP-1 was related to current treatment with ACEI and beta-blockers (p<0.05). In the 104 patients with a normal LV ejection fraction, only PIIINP was related to SPECT-ischaemia (4.1+/-2.2 microg L-1 vs. 3.1+/-1.5 microg L-1, p=0.01). CONCLUSION: In patients with chronic CAD, exercise ischaemia is associated with increased collagen-III turnover, independently of concomitant medications and even when LV ejection fraction is normal. Long-term, this increase might relate to adverse cardiac remodelling even when cardiac function is not clearly affected at baseline.

French adaptation and preliminary validation of a questionnaire to evaluate understanding of informed consent documents in phase I biomedical research.

The content of informed consent documents (ICD) is a crucial element in the process of providing information to participants in biomedical research. Clear comprehension of the information, i.e. the ability to understand its meaning and its consequences, is of utmost importance. The objective of this study was to describe the different steps in the French adaptation and preliminary validation of the Qualité de Compréhension des Formulaires d'information et de consentement (QCFic) questionnaire (http://www.lyon.inserm.fr/cic-grenoble) based on the American Quality of Informed Consent (QuIC) questionnaire. Adaptation and preliminary validation of the QuIC for use in France was composed of five principal steps: translation, scientific validation, lexical validation, edition of gold-standard answers and a pilot study. Each stage was conducted by independent groups of experts, under the coordination of the study board. Thirteen questions were added and one was suppressed. Two steps were required for the scientific validation and for lexical validation, 21 modifications were proposed. Relative to gold-standard answers, the three experts gave the same answer for 24 questions and for nine other questions, two of the three gave identical answers, which were validated by the study board. Results of a pilot study showed a global QCFic score of 88.99 (84.13-90.92) and no specific commentary was made about the content of the questions, so no more modification needed to be made. A preliminary validated French questionnaire, the QCFic, is now available to evaluate the quality of an informed consent document in phase I clinical trials. It is quick and easy to use.

Early changes in serum markers of cardiac extra-cellular matrix turnover in patients with uncomplicated hypertension and type II diabetes.

AIMS: Extracellular matrix (ECM) turnover is a major determinant of diastolic dysfunction and pumping capacity, thus potentially contributing to the progression of congestive heart failure (CHF). Patients with both arterial hypertension and diabetes have a high risk of heart failure. Whether these patients have changes in cardiac ECM has not been studied previously. Our objective was to compare blood markers of collagen turnover among patients with CHF, patients with hypertension and type II diabetes (HD), and healthy individuals. METHODS AND RESULTS: Measurements were performed in 239 CHF patients; 64 HD patients and 92 healthy subjects. We showed by adjusted ANOVA that PIIINP levels were significantly higher in CHF and HD patients than in controls, and higher in CHF patients than in HD patients. MMP1 levels were significantly lower in CHF and HD patients than in controls. Collagen type I markers (PICP and PINP) were not influenced by CHF but were lower in HD patients as compared to controls (p<0.05 for all comparisons). CONCLUSION: In heart failure, markers of cardiac collagen synthesis are increased and markers of degradation are decreased, potentially contributing to cardiac fibrosis and thus to poor outcome. Changes in collagen turnover may also occur early in the disease process in high-risk patients before heart failure is clinically detectable.

Effect of MR blockade on collagen formation and cardiovascular disease with a specific emphasis on heart failure.

Collagen is the major extracellular matrix protein in the heart and represents a crucial target for anti-remodeling and cardioprotective therapy. Collagen quantity and quality have been shown to be regulated under various physiological and pathologic conditions. Excessive deposition of collagen, leading to cardiac fibrosis, is a major determinant of cardiac dysfunction and arrhythmogenecity associated with sudden death. Serological markers of collagen turnover were proven as a noninvasive reliable tool for monitoring from a distance cardiac tissue repair and fibrosis, both in experimental and clinical conditions. Some markers of collagen synthesis and degradation were shown to have a prognostic significance in myocardial infarction, cardiomyopathy and heart failure, and were reported as independent predictors of mortality. Aldosterone represents the end-product of the renin angiotensin aldosterone system and may play a role in cardiac collagen deposition independent of its effect on blood pressure. Production of aldosterone is mainly regulated by angiotensin II and is activated in the failing human ventricle in proportion to heart failure severity. Circulating or locally produced aldosterone stimulates fibrillar collagen accumulation in the heart directly via mineralocorticoid receptors or, indirectly, modifying angiotensine II receptors number and/or function. The use of mineralocorticoid receptor antagonists counters collagen deposition, even when used on top of classical RAAS inhibitors, such as ACE inhibitors and angiotensine II receptor blockers. There is now accumulating evidence from experimental and clinical studies showing antifibrotic and cardioprotective effect for aldosterone antagonists, spironolactone and eplerenone. In chronic heart failure and post myocardial infarction patients, aldosterone receptor blockade benefit was associated with decreased serum levels of collagen synthesis marker PIIINP (procollagen type III amino-terminal peptide), without affecting collagen degradation. Understanding various autocrine/paracrine mechanisms involved in extracellular matrix remodeling in heart failure represents a major challenge, essential for developing new cardioreparative and cardioprotective strategies.

Impact of French 'Comités de Protection des Personnes' on the readability of informed consent documents (ICD) in biomedical research: more information, but not better information.

Information is the keystone to the participation of subjects in biomedical research. Clear comprehension of the informed consent documents (ICDs) is primordial and a necessary requirement is that they are readable. While submission of a protocol to a French 'Comités de Protection des Personnes' (CPP) is a mandatory step with regard to the French legislation on biomedical research, no published data are available concerning its influence on ICDs readability. The aim of our study was to determine the impact of French CPP on the readability of ICDs, using lexico-syntactic readability indexes and ICDs from four clinical research centres and one clinical research unit. Twenty-five ICDs were analysed. The Flesch score was not modified after CPP review, while the Cordial score was significantly lower [from 4 (1-14) to 1 (1-13), P = 0.014]. The information was longer and more complex following CPP review. No protocol characteristics had any impact on the variation before and after review for either the Flesch or the Cordial indexes, nor on the number of syllables per word. Changes in the total number of words before and after review varied considerably between study centre, supporting heterogeneity of CPP review. Since August 2004, French CPP have to study the intelligibility of ICDs in addition to the scientific and ethic aspects of a research. We show that their current reviews do not increase the readability, while increasing the length of ICDs.

[Performance evaluation of a tool for institutional protocol quality assurance]. / Evaluation de la performance d'un outil d'assurance qualité des protocoles institutionnels.

BACKGROUND: Few data are available on the quality of the protocols promoted by the University Hospital Centers (CHU) in France, and there is no standardised method for evaluating protocol quality. The Clinical Research Centre (CIC) of Nancy developed a checklist-based tool aimed at evaluating the quality of institutional protocols. OBJECTIVE: The objective of this study was to evaluate the performance of this tool for assessing the quality of the protocols promoted by the CHU. METHODS: A prospective parallel-group study design, controlled with cluster randomisation, was used. The checklist was applied within the Directions of Clinical Research (DRC) for 4 months. Sixty four protocols were analysed. RESULTS: Before intervention there was no significant difference in quality scores between the two groups. Compared with baseline, there was a significant improvement of the methodological and regulation median score (81.7 +/- 13.7 vs 90.4 +/- 9.2) only in the intervention group (p = 0.040). Changes in the two groups over time were not significantly different from each other using analysis of variance (p = 0.501). CONCLUSION: In an observation limited to 12 CHU in France, the quality of the promoted protocols was judged as suboptimal and able to be improved. Initiation of quality assurance tools, such as the one used in this study, was associated with some spontaneous improvement, but did not improve the result significantly.

[Proposal of a tool for providing patients with the main results of clinical research studies]. / Proposition d'un outil de transmission au patient des résultats globaux de la recherche biomédicale.

CONTEXT: Clinical research regulations currently undergo major revisions mainly initiated by the European harmonization. Regulations must indeed all be adapted to the contents of directive 2001/20/CE applicable in France on 1 May 2004. One of the four principal modifications of the Huriet-Sérusclat law dating from 4 March 2002 relates to the transmission of the main results of research protocols to participating patients. However, no precise directives or information are provided to investigators and sponsors on how to implement this. OBJECTIVE: Our objective was to create a tool to assist investigators providing patients with the main results of clinical research studies. MATERIALS AND METHODS: We first consulted the various participants in biomedical research: ethics committee (CCPPRB), Clinical Investigation Centres (CIC), institutional sponsors, participating patients, plus research protocols and lawyers specialized in forensic medicine. CONCLUSION: After analysis of their answers, we worked out the bases of our tool. This tool is tested in an implementation phase.

Differential time effect profiles of amlodipine, as compared to valsartan, revealed by ambulatory blood pressure monitoring, self blood pressure measurements and dose omission protocol.

Amlodipine and valsartan are once-daily antihypertensive agents. To date, no comparison between these agents given as monotherapies was reported. This study was aimed to evaluate the therapeutic coverage and safety of amlodipine and valsartan in mild-to-moderate hypertensive patients. Multicenter, double-blind, randomized, comparative study. After a 4-week placebo wash-out period, 246 outpatients with office diastolic blood pressure 95 < or = DBP < or =110 mmHg and systolic blood pressure (SBP) < 180 mmHg, in addition to a mean daytime SBP and/or DBP > 135/85 mmHg on 24-h ambulatory blood pressure monitoring (ABPM), were randomly allocated to once-daily amlodipine 5-10 mg or valsartan 40-80 mg, for 12 weeks. In a subgroup of patients, 48-h ABPM were performed at the end of the treatment period. Dose omission was simulated by a single-blind placebo dosing. The primary efficacy end-point was the 24-h trough office BP after 12 weeks of active therapy. The reductions in 24-h trough BP were more pronounced in amlodipine compared with valsartan group as well in office [SBP: -17.8 +/- 10.9 vs. -14.6 +/- 11.2, P = 0.025, DBP: -12.7 +/- 7.2 vs. -10.9 +/- 7.8 mmHg, P = 0.06) as in ambulatory BP (SBP/DBP: -13.0 +/- 13.7/-10.8 +/- 9.1 vs. -7.2 +/- 19.4/-4.9 +/- 13.4 mmHg, P < 0.05). Forty-eight hours after the last active dose, the slope of the morning BP surge (4-9 h) was less steep with amlodipine vs. valsartan [DBP (P < 0.04), SBP (n.s.)]. Ankle edema were more often reported in amlodipine group. These results suggest a superior BP lowering and a longer duration of action with amlodipine compared with valsartan.