Generational changes in multiple sclerosis phenotype in North African immigrants in France: A population-based observational study.

BACKGROUND: The incidence of multiple sclerosis (MS) changes from generation to generation in ethnically different immigrants compared with native-born people. We aimed to determine whether there are generational changes in MS phenotypes among North African immigrants in France. METHODS: Cohort study with data from a population-based MS registry to compare the clinical characteristics of 80 first (NAG1) and 167 second (NAG2) generation North Africans with MS living in France with 5200 native-born Europeans. Adjusted Cox models were used to test the association between scores of 3 and 6 on the expanded disability status scale (EDSS) and the "origin/generation" variable. RESULTS: Cox models for EDSS scores 3 and 6 showed a higher risk of score 3 (hazard ratio = 1.738, 95% confidence interval 1.237 to 2.444; P = .002) and 6 (hazard ratio = 2.372, 95% confidence interval 1.626 to 3.462; P<.0001) for NAG1 than Europeans. Being NAG2 was not significantly associated with higher hazards of scores 3 and 6. CONCLUSIONS: We found two different phenotypes among NAG1 and NAG2 MS patients in France. NAG1, but not NAG2, have a higher risk of disability than Europeans. This raises the question of environmental factors in MS expression, and advocates appropriate patient management according to generation in immigrants.

[Acetaminophen: Knowledge, use and overdose risk in urban patients consulting their general practitioner. A prospective, descriptive and transversal study]. / Le paracétamol : connaissance, usage et risque de surdosage en patientèle urbaine de médecine générale. Étude prospective descriptive transversale.

INTRODUCTION: Acetaminophen is the most involved active substance in both unintentional and intentional drug poisoning. However, its availability outside community pharmacies is being debated in France. METHODS: We made, via a self-administered questionnaire, a prospective assessment of knowledge, use and acetaminophen overdose risk in patients consulting their general practitioner, in the Metz Métropole urban area, between May 2015 and February 2016. We estimated the prevalence of potential unintentional overdosage by capture-recapture method. RESULTS: Among 819 responding patients, only 17.9 % had a sufficient knowledge and 20.3 % were at risk for potential unintentional overdose. The risk was higher for patients aged over 55 years or belonging to socioprofessional categories of laborers and inactive. A good knowledge score was a protective factor for overdose risk (P<0.0001). The liver toxicity of acetaminophen was particularly unknown. The prevalence of potential unintentional acetaminophen overdose was estimated at 1 to2 % of the population. CONCLUSION: Proposing acetaminophen outside of pharmacies cannot be recommended in France in such conditions. Information campaigns are needed to limit the risk of unintentional overdose and its consequences on liver toxicity.

[Good use and knowledge of paracetamol (acetaminophen) among self-medicated patients: Prospective study in community pharmacies]. / Étude prospective en pharmacie du bon usage et de la connaissance du paracétamol pris en automédication.

Acetaminophen (paracetamol), the highest over-the-counter (OTC) selling drug in France, is also the first cause of acute hepatic failure. We aimed to assess the good use and the knowledge of acetaminophen in a setting of urban self-medicated patients. We conducted a prospective observational study in randomly selected community pharmacies of Metz (France) agglomeration. Patients coming to buy OTC acetaminophen for themselves or their family had to answer to an anonymous autoquestionnaire. Responses were individually and concomitantly analyzed through 3 scores: good use, knowledge and overdosage. Twenty-four community pharmacies participated and 302 patients were interviewed by mean of a dedicated questionnaire. Most of patients (84.4%) could be considered as "good users" and independent factors of good use were (i) a good knowledge of acetaminophen (OR=5.3; P<0.0001) and more surprisingly; (ii) the fact of having no children (parentality: OR=0.1; P=0.006). Responses corresponding to involuntary overdosage were mostly due to a too short interval between drug intakes (3hours). Only 30.8% of patients were aware of liver toxicity of acetaminophen and only 40.7% knew the risk of the association with alcohol. Both good use and knowledge were significantly higher in patients looking for information from their pharmacist, physician and package leaflet. Patients should definitely be better informed about acetaminophen to warrant a better safety of its consumption. Pharmacists and physicians have to remind patients the risk factors of unintentional overdose and liver toxicity. Package leaflets have also to be more informative.

10-year cumulative and bidirectional associations of domain-specific physical activity and sedentary behaviour with health-related quality of life in French adults: Results from the SU.VI.MAX studies.

BACKGROUND: The directionality of the associations of domain-specific physical activity (PA) and sedentary behaviour (SB) with health-related quality of life (HRQoL) in adults remain insufficiently known. This study investigated the longitudinal associations of 10-year cumulative levels of PA and SB with HRQoL and the reverse associations. METHODS: A sample of 2093 (47.8% men) participants from a cohort of French adult (SU.VI.MAX) was included. Data were collected at 3 time points (1998, 2001 and 2007) using the Modifiable Activity Questionnaire (MAQ) for PA (leisure-time and occupational) and SB (screen-viewing, reading and total sitting time) and the DUKE Health Profile for HRQoL. The cumulative level (from 0 to 3) referred to the number of time points where a high PA level, high SB or good HRQoL was reported. Regression models examined the 10-year cumulative level of PA, SB as predictors of HRQoL and reverse associations. RESULTS: The 10-year cumulative level of high PA, both leisure-time and occupational, predicted a higher HRQoL while the 10-year cumulative level of high screen-viewing time and high total sitting time was associated with lower HRQoL. For the reverse association, cumulative level of good HRQoL predicted more leisure-time PA, less screen-viewing time and less total sitting time but was not related to occupational PA. CONCLUSION: Relationships between PA, SB and HRQoL are complex and should not be oversimplified in one or the other direction. Taking into account domain-specific PA and SB in health promotion programs appears of prime importance to design interventions aiming at improving HRQoL.

No prognostic value of routine cerebrospinal fluid biomarkers in a population-based cohort of 407 multiple sclerosis patients.

BACKGROUND: We aimed to determine the association of clinical and routine cerebrospinal fluid biochemical markers (total protein, IgG index and oligoclonal bands) with disability in multiple sclerosis and whether these biomarkers assessed at diagnosis add prognostic value. METHODS: We followed a cohort of patients included in the Multiple Sclerosis Lorraine Register (eastern France) who had a diagnosis of multiple sclerosis for at least 5 years, as well as biological markers values and MRI findings (Barkhof's criteria). In a Cox regression model, endpoint was time to score of 4 on the Expanded Disability Status Scale (EDSS) (i.e., limited time walking without aid or rest for more than 500 m). RESULTS: For 407 patients included, the median time from multiple sclerosis onset to EDSS score 4 was 4.5 years [2.2-7.2]. Cerebrospinal fluid total protein factor < 500 mg/L was associated with EDSS score 4 on bivariate analysis (hazard ratio 0.66, 95% confidence interval 0.46-0.95, p = 0.02). On multivariate analysis, older age at disease onset (≥50 years) and initial primary progressive course of MS but not biological markers predicted worse prognosis. CONCLUSION: Routine cerebrospinal fluid biological markers at diagnosis were not prognostic factors of multiple sclerosis progression.

Neutralizing antibodies and fatigue as predictors of low response to interferon-beta treatment in patients with multiple sclerosis.

BACKGROUND: The clinical impact of neutralizing antibodies against interferon-beta (NAb) is controversial. Their presence can lead to a decrease in interferon-beta (IFNß) efficacy. Fatigue reported in patients with multiple sclerosis (MS) may be associated with an unfavorable clinical course. We conducted a prospective multicentre study to assess the association between response to IFNß, NAb and fatigue. METHODS: Patients with relapsing-remitting MS on IFNß treatment were included. During the second year of treatment, the patients were analyzed for NAb status and non-response criteria to IFNß (number of relapses ≥1 during the follow-up period, increase in the Expanded Disability Status Scale ≥0.5). The score on the Modified Fatigue Impact Scale (MFIS pathological if score ≥35) was noted for each patient. RESULTS: Of the 176 patients included: 22.3% were NAb positive, 54.5% presented non-response criteria to IFNß, and 57.4% had a pathological MFIS score. Fatigue was increased in NAb + patients (p = 0.0014) and they were more likely to present non-response criteria to IFNß (p = 0.041) than NAb- patients. Multivariate logistic regression analysis showed that the presence of NAb was related to fatigue (p = 0.0032) and denoted disease activity in these patients (p = 0.026). CONCLUSIONS: This study demonstrates the impact of NAb on the non-clinical response to IFNß. Fatigue assessment is an indicator of IFNß responsiveness and a predictive biomarker of deterioration on patient's neurological status.

Additional use of Aß42/Aß40 ratio with cerebrospinal fluid biomarkers P-tau and Aß42 increases the level of evidence of Alzheimer's disease pathophysiological process in routine practice.

BACKGROUND: Cerebrospinal fluid (CSF) biomarkers have recently been included in the criteria for the diagnosis of Alzheimer's disease (AD). Since interpretation of CSF profile requires the combination of three parameters, biological data are not always conclusive and isolated elevation of phosphorylated tau (P-tau) or reduction of amyloid-ß (Aß)42 alone can be observed. In these cases, Aß42/Aß40 ratio could be more relevant than Aß42 absolute values by considering inter-individual variations in the total amyloid load. OBJECTIVE: The objective of this study was to assess the use of Aß42/Aß40 ratio to improve the accuracy of biological conclusions in the diagnosis of patients with ambiguous CSF Aß42 or tau results. METHODS: Among 386 lumbar punctures analyzed in the lab in 2 years, 122 showed ambiguous biological data that were completed by CSF Aß40 quantification and Aß42/Aß40 ratio calculation. A biological conclusion was then made using 0.05 as the Aß42/Aß40 ratio cut-off. RESULTS: Our results showed that one-third of the biological profiles of patients with atypical dementia were ambiguous. The addition of Aß42/Aß40 ratio increased the proportion of interpretable biological profiles from 69% to 87%, without changing the conclusion when usual biomarkers (Aß42 and P-tau) were concordant. CONCLUSION: Our results support the use of the Aß42/Aß40 ratio in addition to the usual CSF AD biomarkers for patients with ambiguous biological profiles. This method could be specifically directed to this population in order to improve the level of certainty for clinical routine practice.

B vitamin and/or n-3 fatty acid supplementation and health-related quality of life: ancillary findings from the SU.FOL.OM3 randomized trial.

BACKGROUND: Despite growing attention to nutrition and quality of life in cardiovascular disease survivors, the impact of dietary factors according to disease type or to quality of life domain is poorly understood. We investigated the effects of B vitamin and/or n-3 fatty acid supplementation on health-related quality of life among survivors of stroke, myocardial infarction, or unstable angina. METHODS: We performed ancillary analyses of the SU.FOL.OM3 trial (2003-2009; France). In total, 2,501 men (mean age = 61 y) and women (mean age = 63 y) were randomized in a 2×2 factorial design to: 1) 0.56 mg 5-methyl-tetrahydrofolate, 3 mg vitamin B6, 0.02 mg vitamin B12; 2) 600 mg eicosapentaenoic and docosahexaenoic acids in a 2∶1 ratio; 3) B vitamins and n-3 fatty acids combined; or 4) placebo. Health-related quality of life was evaluated at follow-up with the Medical Outcomes Study 36-Item Short Form Health Survey. Data from 2,029 individuals were used in this analysis. RESULTS: After 3.1±0.4 y, no effects of supplementation with either B vitamins or n-3 fatty acids on quality of life (physical or mental health domains) were found. However, participants receiving B vitamins had slightly more activity limitations due to emotional problems compared with those not receiving B vitamins (mean difference = 3.8; 95% CI: 0.4, 7.1). A significant interaction of treatment by prior disease revealed an inverse association between n-3 fatty acids and vitality among myocardial infarction survivors (mean difference = 2.9; 95% CI: 0.5, 5.2). CONCLUSIONS: There were no beneficial effects of supplementation with relatively low doses of B vitamins or n-3 fatty acids on health-related quality of life in cardiovascular disease survivors. The adverse effects of B vitamins on activity limitations and of n-3 fatty acids on vitality among individuals with prior myocardial infarction merit confirmation.

Does compliance with nutrition guidelines lead to healthy aging? A quality-of-life approach.

OBJECTIVES: We aimed to estimate, in a large French cohort of middle-aged adults derived from the Supplémentation en Vitamines et Minéraux Antioxydants trial, the association of compliance with the guidelines of the French Nutrition and Health Program (PNNS) assessed at inclusion and change in health-related quality of life (HRQoL) over 12 years. A secondary objective was to identify the relative contribution of diet and physical activity to long-term change in HRQoL. DESIGN/SUBJECTS: Subjects were Supplémentation en Vitamines et Minéraux Antioxydants trial participants aged 45 to 60 years at inclusion in the cohort. MAIN OUTCOME MEASURES: Compliance with nutrition guidelines (diet and physical activity) was assessed by the PNNS Guideline Score (maximum 15 points) at inclusion. HRQoL was measured by the Medical Outcomes Survey Short Form 36 (SF-36) at 1 year (initial measurement) and 13 years (final measurement) after inclusion. The primary end point was change in the SF-36 physical component summary (PCS) and mental component summary (MCS) scores over 12 years. RESULTS: In total, 3,005 subjects (mean age 51.4 ± 4.3 years) completed the SF-36 at the initial and final measurement. The mean PNNS Guideline Score was 7.8 ± 1.9 and the mean PCS and MCS was 52.2 ± 6.4 and 50.3 ± 7.0, respectively, at the initial measurement and 48.0 ± 9.6 and 51.2 ± 8.7 at the final measurement. Better compliance with nutritional guidelines was associated with better initial and final HRQoL but not associated with change in HRQoL. Compliance with dietary guidelines was associated with positive change in PCS score but not associated with initial PCS score. In contrast, compliance with dietary guidelines was related to positive initial MCS score but not related to change in MCS score. Compliance with physical activity guidelines was related to initial PCS and MCS scores but not related to change in PCS and MCS scores. CONCLUSIONS: Following physical activity guidelines may be associated with better concomitant HRQoL and following dietary guidelines with better future physical HRQoL.

Intervention dose estimation in health promotion programmes: a framework and a tool. Application to the diet and physical activity promotion PRALIMAP trial.

BACKGROUND: Although the outcomes of health promotion and prevention programmes may depend on the level of intervention, studies and trials often fail to take it into account. The objective of this work was to develop a framework within which to consider the implementation of interventions, and to propose a tool with which to measure the quantity and the quality of activities, whether planned or not, relevant to the intervention under investigation. The framework and the tool were applied to data from the diet and physical activity promotion PRALIMAP trial. METHODS: A framework allowing for calculation of an intervention dose in any health promotion programme was developed. A literature reviews revealed several relevant concepts that were considered in greater detail by a multidisciplinary working group. A method was devised with which to calculate the dose of intervention planned and that is actually received (programme-driven activities dose), as well as the amount of non-planned intervention (non-programme-driven activities dose). RESULTS: Indicators cover the roles of all those involved (supervisors, anchor personnel as receivers and providers, targets), in each intervention-related groups (IRG: basic setting in which a given intervention is planned by the programme and may differ in implementation level) and for every intervention period. All indicators are described according to two domains (delivery, participation) in two declensions (quantity and quality). Application to PRALIMAP data revealed important inter- and intra-IRG variability in intervention dose. CONCLUSIONS: A literature analysis shows that the terminology in this area is not yet consolidated and that research is ongoing. The present work provides a methodological framework by specifying concepts, by defining new constructs and by developing multiple information synthesis methods which must be introduced from the programme's conception. Application to PRALIMAP underlined the feasibility of measuring the implementation level. The framework and the tool can be used in any complex programme evaluation. The intervention doses obtained could be particularly useful in comparative trials. TRIAL REGISTRATION: PRALIMAP is registered at ClinicalTrials.gov under NCT00814554.

Integration of cognitive impairment in the expanded disability status scale of 215 patients with multiple sclerosis.

BACKGROUND: Estimates of the prevalence of cognitive impairment among patients with multiple sclerosis (MS) range between 40 and 70%. The current cerebral functional system (CFS) of the Expanded Disability Status Scale (EDSS) is subjective. AIM: To define a new cerebral functional system (NCFS) based on neuropsychological evaluation (NE). METHODS: We prospectively included 215 MS patients. NE evaluated cognitive functions. Fatigue was assessed with the Fatigue Impact Scale. The NCFS was devised with grades from 0 to 5, excluding depression but including fatigue. Grade 1 of the NCFS was integrated in the EDSS as other functional scores. The NCFS and new EDSS including the NCFS were compared with the current CFS and EDSS. RESULTS: 215 patients (69% women, 67% with relapsing-remitting MS, median EDSS 3.0) were assessed. 98% of these patients presented fatigue and/or cognitive impairment with the NCFS compared to 62% with the CFS. The NCFS was higher than the CFS, and the EDSS had changed in 31% of the 113 patients with an EDSS <3.5. Change in functional score was not correlated to current age or age at onset of MS. CONCLUSIONS: We propose a new CFS grading based on NE, including fatigue, and integrating grade 1 at EDSS.

Comparison of two-year outcomes in patients undergoing isolated coronary artery bypass grafting with and without peripheral artery disease.

We aimed to evaluate the long-term clinical outcomes among patients with peripheral arterial disease (PAD) after coronary artery bypass grafting. We studied 589 consecutive patients who had undergone isolated coronary artery bypass grafting from January 2003 to June 2005 at our university hospital. The effect of PAD was assessed by comparing the 2-year follow-up data from 2 groups of patients: 243 patients with and 346 without PAD. A large systematic atherosclerosis screening was performed, including cerebrovascular disease, lower extremity artery disease, and abdominal aorta disease and its branches. PAD was defined as a history of treated atherosclerotic disease and significant atherosclerotic stenosis on screening. Patients with PAD were significantly older (70 +/- 9 vs 64 +/- 11 years, p <0.001) and were more often men (p = 0.04) than those without PAD. They had a greater incidence of hypertension (p = 0.002), chronic renal dysfunction (p <0.01), chronic pulmonary disease (p = 0.005), and a history of coronary artery disease (p = 0.03). No significant difference was noted between the 2 groups with regard to the left ventricular ejection fraction. The 2-year cumulative survival rate was 76.6% for patients with PAD and 94.1% for those with isolated coronary disease (p <0.001). In conclusion, after adjusting all significant variables, the presence of PAD appeared as an independent predictive factor for all-cause mortality (adjusted hazard ratio 3.2, 95% confidence interval 1.8 to 5.7, p = 0.001).

[Provider delays among patients with breast cancer in a Regional Cancer Care Network: feasibility of personal care schedule]. / Délais de prise en charge des patientes atteintes d'un cancer du sein dans un réseau régional de soins en cancérologie: faisabilité d'un programme personnalisé de soins.

In order to determine the feasibility of a personal care schedule, we studied provider delays among women with breast cancer in hospitals of a French Regional Cancer Network. In 2001, 148 women have been treated by surgery in the Alexis Vautrin Comprehensive Cancer Centre (AVCCC), then by adjuvant chemotherapy and radiotherapy. Before surgery, individual variations in delays was observed: from 0 to 65 days between the appointment making and the first consultation, from 3 to 108 days to start the treatment. After surgery, no significant difference in delays was found between women treated at AVCCC and those managed in another network institution (average delays: 35 days between surgery and chemotherapy, 4 months for chemotherapy, 3 weeks between chemotherapy and radiotherapy, and 35 days for radiotherapy). These results suggest an efficient organisation that allow to establish a personal care schedule for each patient after providing anatomopathological data.