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Melatonin secretion occurs at a constant rate in both young and older men and women. Am J Physiol Endocrinol Metab 280: E11-E22, 2001.--The magnitude and duration of melatonin (MLT) secretion were measured over a period of 25 h with pharmacokinetic studies employing administration of [D.sub.7] MLT at midday and at midnight in two separate studies and two groups of subjects, 12 young and 11 older men and women. Plasma levels of endogenous MLT and [D.sub.7] MLT were quantified separately by use of a specific and sensitive method (gas chromatography-mass spectrometry) previously developed in our laboratory, enabling us to measure endogenous and exogenous MLT levels down to 0.5 pg/ml in plasma. In the two groups of subjects, MLT secretion occurred only at night: onset time of secretion was from 1915 to 2205 (Greenwich mean time), and offset was from 0305 to 0545. No MLT peak was observed in individual nocturnal MLT profiles that were similar to curves obtained for a rate-constant infusion. Modelization demonstrated the superimposition of observed data and simulated curves. MLT concentrations decreasing from the offset of secretion might correspond to the elimination of MLT present in the body at the end of nocturnal secretion. By use of the MLT clearance given by pharmacokinetics, the amount of secreted MLT was found to be 35.7 and 21.6 [micro]g for men and women, respectively, and the rate of secretion was 4.6 and 2.8 [micro]g/h, respectively. No significant gender difference was observed for these two parameters when normalized to body weight. No significant gender difference was observed for onset times of secretion or duration of secretion (7.6-8.6 h) within the two groups, or between young and older subjects. endogenous melatonin; nocturnal secretion; young and elderly subjects; amount of melatonin; rate of secretion

BACKGROUND: The risk of exposure to hepatitis C virus increases markedly in adolescence, and students are thus a preferential target for information campaigns. The aim of this study was to evaluate the results of a hepatitis C information campaign targeting secondary-school students. METHODS: The study was done in 52 classes of 11 general and vocational secondary schools. Before the information meetings and two months afterwards, the students received an anonymous questionnaire to test their knowledge of hepatitis C. The information session was backed up by a comic strip depicting scenarios involving hepatitis C. RESULTS: The students were aged from 14 to 24 years (mean 15.9 years, SD 0.9 years). Respectively 1509 and 1419 questionnaires were completed before and after the information session. Answers to the first questionnaire showed that the students' knowledge of hepatitis C was poor. Scores improved significantly after the information session, from an overall mean of 6.2 (SD 2.0) to 8.5 (SD 1.7) (p<0.001). The largest score improvement concerned transmission due to illicit drug use, the potential severity of the disease, and lack of a vaccine. The improvement was significantly larger among pupils who said they read the comic strip than among those who did not (p=0.02). CONCLUSIONS: General and vocational secondary school students in France have mediocre knowledge of hepatitis C, particularly its modes of transmission and the lack of a vaccine. Knowledge improved significantly when measured two months after an information session, suggesting that subsequent at-risk behaviours might be reduced. [ABSTRACT FROM AUTHOR]

Pharmacokinetic interaction between ponsinomycin-nicoumalone was studied in six subjects who received an 8 mg oral dose of racemic nicoumalone alone and 4 days into an oral regimen of ponsinomycin 800 mg twice daily. The concentrations of R(+) and S(-)-nicoumalone in plasma were measured using a stereospecific h.p.l.c. assay. The disposition characteristics of nicoumalone enantiomers in the control phase of this study were similar to those reported previously with the exception of the data for one subject whose oral clearance for S(-)- nicoumalone was seven times lower than those in the other subjects. A statistically significant effect of ponsinomycin on the kinetics of R(+) and S(-)-nicoumalone was not demonstrated. [ABSTRACT FROM AUTHOR]

Abstract Background Several studies have shown the influence of the perceptions of aging on the cognitive functioning and the mental and physical health of older people. These relationships have not to date been studied in France where validated instruments are lacking. The primary objective of this study was to validate a French-language version of the Aging Perceptions Questionnaire (APQ) in the French general population aged 65 and over. The secondary objective was to study the stability of the dimensions of this instrument among participants aged 55 to 64. Methods The study was proposed to the cohort of the Observatoire Régional du Vieillissement (OPREVI) (observatory of aging), located in a small town in Poitou-Charentes (western France). An anonymous questionnaire including the APQ was sent by mail to inhabitants aged 55 and over. The original English language APQ was described with adults aged 65 and older. It has 32 items distributed on 7 dimensions: timeline chronic and cyclical, positive and negative consequences, positive and negative control and emotional representations. Results 656 adults participated in this survey (286 men, 370 women). Among those aged 65 and over (n = 394), the seven-factor structure estimated by confirmatory factor analysis was coherent with original findings. Internal consistency as evaluated by Cronbach alpha, was between 0.83 for consequences negative and 0.52 for control negative. Several dimensions were strongly correlated. Among participants aged 55 to 64 (n = 262), the same factorial model yielded an acceptable fit. Multi-group confirmatory factor analysis concluded to approximate factorial invariance between the two age groups with a null delta in comparative fit index. Conclusion This study among French people aged 65 and over, added further evidence of the multidimensional structure of the French version of the APQ which is superimposed to the dimensions of the original Irish version. The same factorial structure applies acceptably to the younger group (aged 55–64). The OPREVI study is ongoing, and will collect data on the physical, material and social characteristics of participants. It will therefore be possible to analyse the variables associated with the perceptions of aging. On the basis of an individual's perceptions of aging as captured by this questionnaire, and his or her clinical profile, tailored multi-dimensional assistance could be made available aiming to provide incentives to anticipate or to adapt to difficulties.

Abstract Background Targeted colonosocopic screening is recommended for first-degree relatives of colorectal cancer patients diagnosed before the age of 60 and offers the possibility of reducing morbidity and mortality, but participation remains too low. The objective of this study was to determine in a French population the factors that affect siblings' participation in screening, notably those relating to the individuals, their medical care, their family and their social network. Methods A cross sectional survey was conducted in siblings of index patients having undergone surgery for colorectal cancer between 1999 and 2002 in two French counties. Siblings were contacted during 2007 and 2008 through the index patient. The factors affecting participation in colonoscopic screening were studied by logistic regression taking into account family cluster effect. Results 172 siblings of 74 index cases were included. The declared rate of undergoing at least one colonoscopy among siblings was 66%; 95%CI 59-73%. Five variables were independently associated with colonoscopic screening: perceiving fewer barriers to screening (OR = 3.2; 95%CI 1.2-8.5), having received the recommendation to undergo screening from a physician (OR = 4.9; 1.7-13.7), perceiving centres practising colonoscopy as more accessible (OR = 3.2, 1.3-7.8), having discussed screening with all siblings (OR = 3.9; 1.6-9.6) and being a member of an association (OR = 2.6; 1.0-6.6). Conclusions The factors independently associated with participation in CRC screening by an individual at increased risk belonged to each of four dimensions relating to his individual psychosocial characteristics, to his relationship with a physician, within the family and social environment. The relevance of these results to clinical practice may help to improve compliance to recommendations in a global preventive strategy including all stages of the information pathway from the physician to the index patient and his relatives.

Abstract Background The care itinerary for cancer involves difficulties that occur in several different areas, whether in the diagnostic procedures, in surgery, or in adjuvant treatment. The aim of this work was to obtain a valid instrument measuring satisfaction among patients with breast cancer and exploring their care itinerary overall. Methods Development phase: Patient focus groups were implemented in two French regions in order to identify areas of satisfaction in relation to the different phases of care provision in breast cancer. On the basis of the literature and the themes and wordings derived from the focus groups, the patients identified several areas of satisfaction, which they found to be partially covered in an American satisfaction measure that has been validated in the French general population (the Consumer Satisfaction Survey in its French version, CSS-VF, 39 items). The patient focus groups suggested adaptation of certain dimensions of this instrument to the potential care providers (37 items) and produced 45 new items in six areas. Validation phase: Using a large sample of patients (cohort of 820 women with invasive non-metastatic breast cancer) approached one month after treatment, this phase selected items that were comprehensible (non-response rate < 10%), non-redundant (r < 0.80) and reproducible (test-retest conducted on a sub-sample of 166 patients). The dimensions were identified by factor analysis on the selected items. Divergent and discriminant validity were assessed (relationships with quality of life questionnaire, comparisons between extreme groups). Results Results were in favour of not inserting additional broken-down items into the CSS-VF and retaining 21 new items. The factor analysis found the initial structure of the CSS-VF (39 items in 9 dimensions) and the 21 new items divide up into four dimensions (listening abilities and information provided by doctors, organisation and follow-up of medical care provision, psychological support, material environment). No redundancy was observed between new items and CSS-VF items. Internal consistency was high. Divergent and discriminant validity were satisfactory. Conclusion Adding four new dimensions to the CSS-VF yielded a valid 60-item instrument for assessment of care provided in breast cancer. These promising results now require further investigations of its responsiveness and its robustness in other linguistic, cultural and healthcare settings.

Impulsivity dimensions have been shown to be associated with smoking status and tobacco use disorder severity. However, it is important to determine the specific impulsivity traits associated with smoking relapse. This study aimed at investigating the associations between impulsivity traits and smoking cessation success among adult smokers at 12 months after a quit attempt. Participants were 68 adult smokers enrolled in a 3-month course of simvastatine or placebo associated with behavioral cessation support, with a 9-month follow-up (ADDICSTATINE study). They were classified in 3 groups according to smoking status: abstinent, reduction ≥ 50%baseline or reduction < 50%baseline at 3 and 12 months. Impulsivity traits were assessed using the UPPS-P-scale. At 12 months, abstainers and participants who reduced smoking by 50% or more had significantly lower scores in negative and positive urgency compared to participants who reduced smoking by less than 50% (p = 0.011 and 0.0059). These urgency traits scores at 12 months were significantly and negatively correlated with smoking reduction at 12 months (p = 0.017 and 0.0012). These impulsivity traits were also associated with the smoking cessation success at 3 months. Patients who were abstinent at 3 months had also lower negative and positive urgency (p = 0.017 and 0.0039). Smoking cessation success at 3 and 12 months were not associated with the other impulsivity traits, sensation seeking, lack of premeditation or perseverance. Our findings suggest that positive and negative urgency are associated with smoking cessation success. Proposing better tailored-based-treatment targeting these impulsivity traits in combination with conventional treatment may help improving smoking treatment success., (© 2024. The Author(s).)

Objectives: This study aims to explore the place of the relative in these triadic consultations and how this influences communication., Methods: A mixed-methods research strategy was used. Triadic consultations for the announcement of cancer progression were recorded and following the 3 participants completed questionnaires comprising mirror-items. Recordings and answers were further investigated in a few semi-structured interviews. Comparison of quantitative responses (questionnaires) used Wilcoxon's test for matched series. Qualitative analyses (consultations, interviews) used grounded theory. Patients were over 18, followed for cancer in palliative phase, excluding brain tumors and malignant hemopathies, and presented renewed disease progression. Relatives were over 18 and authorized by the patient to participate., Results: 47 consultations (audio-recordings, answers to questionnaires) and 12 interviews conducted separately with 4 triads were collected. Half the relatives, while remaining in the background, nevertheless contributed to the discussion. For patients, the presence of a relative was considered beneficial and for oncologists it facilitated the announcement. However, symptoms perceived as intimate or private appeared difficult to express for some patients, and for relatives, prognosis was a difficult subject to broach. Although their relationship with time and their expectations may differ, patients and relatives found consultations positive. Oncologists appeared to underestimate the patient's level of understanding ( P <0.001) and perceptions of the seriousness of the disease ( P =0.009) but not those of relatives. They did not evaluate the relative's state of health and check what the dyad had retained., Significance of Results: Training via simulation sessions should be adapted to communication involving relatives.

Background: Screening of colorectal cancer (CRC) can reduce incidence and mortality. First-degree relatives (FDRs) of patients with CRC or advanced adenoma before the age of 65 (index patients) are at increased risk of CRC; however, the guidelines for screening of FDRs by colonoscopy are poorly followed., Objectives: The present study, conducted in the context of the COLOR3 interventional study project, aimed to explore the positioning of general practitioners (GPs) in familial CRC screening in France., Methods: From February 2020 to April 2021, 35 semi-structured interviews with GPs of index patients and/or their FDRs were conducted by telephone. The full-data transcribed corpus was subjected to horizontal thematic analysis., Results: Knowledge and compliance with the guidelines vary greatly between GPs. Although initiating the diagnostic process, GPs do not consider themselves as actors in the flow of information concerning familial risk. Their accompaniment of index patients in this role varies. GPs should overcome barriers to implementing colonoscopic screening for FDRs. They underline the importance of exploring family history, but they lack the time and doubt the reliability of the information given by FDRs., Conclusion: Challenges include circumventing gaps in knowledge, adherence to guidelines and improving family history updates. The GPs interviewed suggested personalised guidelines in specialists' reports to initiate information campaigns raising awareness of familial risk, and to enhance coordination between organised screening and familial screening.

Introduction: The professional situation of patients treated for childhood cancer differs from country to country. The aim of the study is to study, with the French sociocultural specificities, the first professional integration of these young people., Methods: A sequential quantitative-qualitative mixed approach associates 16 individual interviews and responses to a self-questionnaire of 254 young cancer survivors (sex-ratio=1, median age 23.5 years diagnosed between 2000 and 2010; 68% leukemia) to 30 individual and collective interviews of professionals. Results They seem to have had fewer difficulties than the general population to find their first job (33% vs. 44%). Young women had more difficulties, young people thought they had stopped studying too early and those who mentioned their sequelae (mainly psychological and neurocognitive). The qualitative phase shows that, in this context, the information provided during the job interview plays an important role in access to the first job., Discussion: The study showed a need for information, communication and training for all actors whose main axes could be: i) for young people: learn to introduce themselves and adapt speeches and postures, be aware of their non-obligation to reveal a situation relating to health and to the handicap; ii) for the medical profession: to promote communication and to find spaces for exchanges between specialists, generalists, occupational physicians; iii) for employers: better know the disease and the laws to adapt their eyes and practices., (Copyright © 2021 Société Française du Cancer. All rights reserved.)

Aim: To assess the efficacy of drugs directly acting on alpha- and beta-adrenergic receptors in the treatment of patients suffering from tobacco or alcohol use disorder., Methods: Using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, studies were identified through PUBMED, EMBASE, the Cochrane Central Register of Controlled Trials and clinicaltrial.gov. We selected only randomized controlled trials with adult patients with tobacco or alcohol use disorders according to DSM-5 criteria. Interventions included any molecule having a direct pharmacological action on alpha- or beta-adrenergic receptors (agonist or antagonist). Comparators were placebo or other validated pharmacotherapies. The duration of the intervention was a minimum of 1 month, with 3 months of follow-up. Measurements included smoking cessation for tobacco; for alcohol, we selected abstinence, alcohol consumption (drinks per day or week) and heavy drinking days (HDD). Ten studies with tobacco and six with alcohol use disorder were included in the qualitative synthesis and fifteen studies in the quantitative analysis., Results: We found that clonidine, an alpha-2 agonist, significantly increased smoking abstinence [relative risk = 1.39 with a 95% confidence interval (CI) = 1.04, 1.84]. Beta-blockers had no significant effect on smoking abstinence. The alpha-1 antagonists prazosin and doxazosin decreased alcohol consumption [SMD = -0.32 (-0.56, -0.07)] but had no effect on abstinence or HDD., Conclusions: The noradrenaline system may represent a promising mechanism to target in tobacco and alcohol use disorders., (©2020 Society for the Study of Addiction.)

Aims: Pharmaco-epidemiological surveys enable the frequency of serious adverse effects-and also the determining factors of their occurrence and seriousness-to be quantified. Few studies systematically gathering post-chemotherapy adverse effects data have been conducted. The objective was to assess the incidence of post-chemotherapy serious adverse effects on the basis of cancer registry data., Methods: The population was composed of new invasive cancer cases, with the exception of haematopoietic tumours and cutaneous carcinomas. These cancers were identified in 2012 among patients living at the time of diagnosis in a region covered by a general cancer registry and by a French regional pharmacovigilance centre, and treated with neo-adjuvant and/or adjuvant first-intention chemotherapy, followed or not by radiotherapy. The study was based on a sample of 1000 patients from the registry, followed by the collection of serious adverse effects and the required information to constitute a pharmacovigilance file., Results: Chemotherapy was associated with a particularly high incidence of serious adverse effects, affecting 44.5% (41.4-47.5%) of the patients. The highest incidence rates were observed when patients were exposed to topo-isomerase II inhibitors such as etoposide and bleomycin (69.2%), vinca-alkaloids (66.7%), topo-isomerase I inhibitors (54.5%) and platinum derivatives (52.0%). The clinical context was also linked to incidence, especially in case of metastases (53.3%) and comorbidities (51.3%). Substantial differences were found according to localisation, with a particularly high incidence in bronchial-pulmonary cancers (59.0%)., Conclusion: The high overall incidence rate of serious adverse effects should motivate a reinforcement of information about drug toxicities and improve knowledge by drawing on patient reporting., (© 2019 The British Pharmacological Society.)

Aims: Despite fluoropyrimidines (FPs) constituting the main component of the chemotherapy combination protocols in 50% of chemotherapies for solid tumour treatments, incidence data for FP-related toxicity are poorly documented in real life. This study evaluated the number of patients receiving FP-based chemotherapies in France, along with the true incidence of FP-related serious adverse effects (SAEs) before the recent mandatory dihydropyrimidine dehydrogenase (DPD)-screening was introduced by French health authorities, DPD being the rate-limiting enzyme of 5-fluorouracil (5-FU) catabolism., Methods: Exhaustive data on the number of patients treated with FP-based chemotherapy in 2013-2014 were collected in the Centre-Val de Loire region of France. True incidence of SAEs was extracted from a cohort of 513 patients with incident solid tumours receiving first-line FP-based chemotherapy., Results: After extrapolation at national level, we estimated that 76,200 patients are currently treated annually with 5FU (53,100 patients, 62% digestive system-related versus 26% breast cancers versus 12% head and neck cancers) or capecitabine (23,100 patients, 45% digestive system-related versus 37% breast cancers versus 18% non-documented). Earlier (in the first two cycles) the SAE incidence rate was 19.3% (95% confidence interval (CI) 16-23%) including one toxic death (0.2%, 95%CI 0-1%). SAE incidence rate was 32.2% (95%CI 28-36%) over the first 6 months of treatment. Incidence of death, life-threatening prognosis or incapacity/disability was 1.4% (95%CI 0.4-2.4%) and 1.6% (95%CI 0.5-2.6%) during first two cycles and first 6 months, respectively., Conclusion: These data highlight the significant public health issue related to FP toxicity, with around 1200 patients developing FP-related life-threatening prognosis or incapacity/disability annually in France, including 150 toxic deaths. It is hoped that DPD-deficiency screening will reduce such iatrogenic events and eradicate toxic deaths., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objective: Information on risk levels is an essential part of the prevention of colorectal cancer (CRC). The objective of this article is to describe a tailored intervention carried out to inform the protagonists about the high risk of CRC due to family history and then to understand, through an interdisciplinary analysis, the mechanisms implemented during the intervention., Method: A randomized trial design was applied. The primary outcome was the colonoscopy uptake. The intervention concerned firstly the index patients with CRC or adenoma to advise and accompany them in the transmission of information about the elevated risk for their siblings. The siblings received tailored counselling carried out by a preventive nurse, by telephone then by mail. Epidemiological, linguistic and sociological cross-analyzes were carried out to understand the impact of the intervention., Results: Colonoscopy rate was 56.3% in the intervention group, 35.4% in the control group (P = 0.0027; 304 siblings). The linguistic analysis of recorded nurse's interventions showed that, following the intervention (N = 59), the prevention themes were better assimilated while they remained vague and questioned in the discourse of the control siblings who had carried out the colonoscopy (N = 8). That was confirmed by the sociological analysis (four families) which also revealed the importance of information received from a health professional and of communication within families., Conclusion: The study showed the impact of transmission of information to convince siblings at high risk of CRC to carry out colonoscopy.

Objectives: To assess the 30-day mortality predictive markers in the oldest patients with Clostridioides difficile infection (CDI) and to analyze the accuracy of the European severity risk markers in this population., Design: Observational prospective multicenter cohort study conducted by the French Infectious Diseases Society and Geriatrics Society networks. An electronic questionnaire was sent to members of both societies regarding their participation. Each investigator used an online survey to gather the data., Setting and Participants: Patients aged ≥75 years hospitalized in French geriatric or infectious wards with confirmed diagnosis of CDI between March 1, 2016 and May 1, 2017., Methods: Clinical and laboratory parameters included medical history and comorbidities with the Cumulative Illness Rating Scale (CIRS). Criteria increasing the risk of severe disease were recorded as listed in the European guidelines. Therapeutic management, recurrence, and mortality rates were assessed at day 30 after diagnosis., Results: Included patients numbered 247; mean age was 87.2 years (SD 5.4). Most of the CDI incidences (66.4%) were health care-associated infections, with 81% diagnosed within 30 days of hospitalization; CIRS mean score was 16.6 (SD 6.6). Markers of severity ≥3 included 97 patients (39.3%). Metronidazole was the main initial treatment (51.0%). C difficile infection in the older adult was associated with a 30-day mortality of 12.6%. Multivariate analysis showed that baseline CIRS score [hazard ratio (HR) 1.06 per 1-point increase, 95% confidence interval (CI) 1.00-1.12] and evidence of cardiac, respiratory, or renal decompensation (HR 3.04, 95% CI 1.40-6.59) were significantly associated with mortality., Conclusions and Implications: European severity markers are adequate in the oldest old. Organ failure and comorbidities appeared to be the main markers of prognosis, and these should raise the awareness of practitioners. Although antibiotic treatment was not predictive of mortality, our results point out the lack of adherence to current guidelines in this population., (Copyright © 2019 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: Information on risk levels is an essential part of the prevention of colorectal cancer (CRC). The objective of this article is to describe a tailored intervention carried out to inform the protagonists about the high risk of CRC due to family history and then to understand, through an interdisciplinary analysis, the mechanisms implemented during the intervention., Method: A randomized trial design was applied. The primary outcome was the colonoscopy uptake. The intervention concerned firstly the index patients with CRC or adenoma to advise and accompany them in the transmission of information about the elevated risk for their siblings. The siblings received tailored counselling carried out by a preventive nurse, by telephone then by mail. Epidemiological, linguistic and sociological cross-analyzes were carried out to understand the impact of the intervention., Results: Colonoscopy rate was 56.3% in the intervention group, 35.4% in the control group (P = 0.0027; 304 siblings). The linguistic analysis of recorded nurse's interventions showed that, following the intervention (N = 59), the prevention themes were better assimilated while they remained vague and questioned in the discourse of the control siblings who had carried out the colonoscopy (N = 8). That was confirmed by the sociological analysis (four families) which also revealed the importance of information received from a health professional and of communication within families., Conclusion: The study showed the impact of transmission of information to convince siblings at high risk of CRC to carry out colonoscopy.

Objective: We conducted a cross-sectional survey in France in a cohort over 55 years of age to characterize the impact of psychological dimensions on quality-of-life (QoL)., Methods: The predictors of QoL in relation with aging were studied using an adapted quality-of-life model, based on emotional, cognitive and physical symptoms, functional status, and general health perception. Adding psychological dimensions such as self-esteem, psychological distress, perceptions of ageing and coping, was hypothesized to improve the QoL model. Responses were analyzed using structural equation modeling and path analysis., Results: The study involved 258 participants, mean age 66.9±7.9 years. Psychological distress and positive perception of aging exhibited the strongest direct impact on QoL (p<0.0001). Psychological distress also appeared to be mediator on QoL for perceived health status, self-esteem and negative perception of aging. Coping centred on emotion exhibited direct impact on self-esteem and so, indirect impact on QoL (p = 0.0002). Perception of personal financial situation (p = 0.0007) and coping centred on social support (p = 0.02) appeared as direct mediators influencing QoL., Conclusions: Psychological dimensions are predictors of QOL and have to be taken into account to maximize the resources with a view to successful aging. Further interventions targeting successful aging should focus on positive perception aging., Competing Interests: The authors have declared that no competing interests exist.

A recent pre-clinical study has shown that brain-penetrating statins can reduce risks of relapse to cocaine and nicotine addiction in rats. Based on this information, we conducted a randomized, double-blind, placebo-controlled, proof-of-concept trial to assess the efficacy of simvastatin in smoking cessation. After informed consent, 118 participants received behavioral cessation support and were randomly assigned to a 3-month treatment with simvastatin or placebo. The primary outcome was biochemically verified abstinence or smoking reduction at 3-month post-target quit date (TQD). Secondary outcomes were abstinence during weeks 9-12 post-TQD, prolonged abstinence or reduction at months 6 and 12 post-TQD, safety and craving assessed at each visit during the 3-month period of treatment. Simvastatin treatment was not associated with higher 3-month abstinence or smoking reduction compared to placebo. There was no significant difference in any of the secondary outcomes. Simvastatin was well tolerated. Over 3 and 9 months follow-up period, 78% simvastatin and 69% placebo participants were retained in the study. At 6 and 12 months, smoking remained significantly reduced from baseline in both groups. Our results demonstrate that a 3-month simvastatin treatment (40 mg/day), added to individual behavioral cessation support, does not improve significantly smoking cessation compared to placebo in humans.

Background/ Objective: Although poorly documented, subcutaneous (SC) administration of antibiotics is common practice in France especially in Geriatrics Departments. The aim of this study was to determine the tolerance of such a practice., Design: Prospective observational multicentre study., Methods: Sixty-six physicians accepted to participate from 50 French Infectious Diseases and Geriatrics Departments. From May to September 2014, patients treated at least one day with SC antibiotics could be included. Modalities of subcutaneous administration, occurrence of local and systemic adverse effects (AE) and clinical course were collected until the end of the treatment., Results: Two hundred-nineteen patients (83.0 [19–104] yo) were included. Ceftriaxone (n = 163, 74.4%), and ertapenem (n = 30, 13.7%) were the most often prescribed antibiotics. The SC route was mainly used because of poor venous access (65.3%) and/or palliative care (32.4%). Fifty patients (22.8%) experienced at least one local AE that led to an increased hospital stay for two patients (4.0%) and a discontinuation of the SC infusion in six patients (12.0%). A binary logistic regression for multivariate analysis identified the class of antibiotic (p = 0.002) especially teicoplanin and the use of rigid catheter (p = 0.009) as factors independently associated with AE. In over 80% of cases, SC antibiotics were well tolerated and associated with clinical recovery., Conclusions: SC administration of antibiotics leads to frequent but local and mild AE. Use of non-rigid catheter appears to be protective against AE. As it appears to be a safe alternative to the intravenous route, more studies are needed regarding efficacy and pharmacokinetics.

Background: Obesity has an impact on health-related quality of life (HRQoL) and bariatric surgery may improve HRQoL in addition to severe obesity-related comorbidities. Aim of the study was to evaluate HRQoL following sleeve gastrectomy and the sensitivity of two HRQoL questionnaires: the Impact of Weight on Quality Of Life-Lite (IWQOL-Lite) and the World Health Organization-Quality Of Life-Bref (WHOQOL-Bref) scales., Methods: Data were prospectively collected from 149 adult patients submitted to laparoscopic sleeve gastrectomy, before, at 6 and 12 months post-operatively. HRQoL was measured using both the WHOQOL-Bref and the IWQOL-Lite questionnaires., Results: Mean age was 40.5±11.9 years, mean initial weight 118.7±30.3 kg and mean preoperative Body Mass Index (BMI) was 44.1±6.3 kg/m². Excess weight loss (EWL) was 53.1% and 68.8% respectively at 6 and 12 months postoperatively. Both questionnaires showed significant improvement of HRQoL 12 months after the procedure. Two over 4 domains (physical and psychological health) of the WHOQOL-Bref improved at 6 months whereas all of the 5 domains of the IWQOL-Lite did. The IWQOL-Lite questionnaire pointed out a significant enhancement both at 6 and 12 months., Conclusions: HRQoL is improved after sleeve gastrectomy. The specific obesity questionnaire IWQOL-Lite seems to be more sensitive than the generic WHOQOL-Bref to detect amelioration of HRQoL.

Background: Colonoscopic screening is recommended for first-degree relatives of patients diagnosed with colorectal cancer (CRC) or colorectal adenomatous polyps (CAP) before the age of 60 years. This has the potential to reduce CRC-related morbidity and mortality, but uptake is currently inadequate., Methods: The aim of the study was to compare the effectiveness of standard information versus a nurse-led tailored intervention designed to promote uptake of colonoscopy screening by siblings of CRC or CAP patients. A randomized controlled trial was conducted. Digestive surgeons and gastroenterologists recruited index patients who developed CRC or CAP before the age of 60 years. All index patients received standard screening information for their siblings, in keeping with current guidelines. Centrally computerized randomization of index patients resulted in allocating all their siblings to the same group, intervention or control. The tailored intervention targeted the index patient first, to help them convey information to their siblings. The nurse then provided the siblings with tailored information based on their answers to a self-questionnaire which explored health behaviors, derived from psychosocial models of prevention. Then the siblings were given a personalized information leaflet to hand to their regular physician. The primary endpoint was the rate of documented colonoscopy performed in siblings within 1 year after diagnosis of the index patient. The intent-to-treat analysis included siblings who refused to participate in the study. Statistical analysis was adjusted for intrafamilial correlation., Results: A total of 304 siblings of 125 index patients were included: 160 in the intervention group and 144 in the control group. The rate of colonoscopy uptake among siblings was 56.3% in the intervention group and 35.4% in the control group (P = 0.0027). The respective rates after exclusion of refusals were 69.2% and 37.0% (P < 0.0001). More lesions were detected in the intervention group (1 invasive cancer and 11 advanced adenomas vs 5 advanced adenomas; P = 0.022)., Conclusions: This study demonstrates the effectiveness of a nurse-led tailored intervention designed to promote colonoscopy screening uptake by siblings of patients diagnosed with CRC or CAP before age 60 years. Such tailored interventions that also involve physicians should help to reduce CRC-related mortality.

To delay age-related bone loss, physical activity is recommended during growth. However, it is unknown whether interval training is more efficient than continuous training to increase bone mass both quickly and to a greater extent. The aim of this study was to compare the effects of a 10-week interval training regime with a 14-week continuous training regime on bone mineral density (BMD). Forty-four male Wistar rats (8 weeks old) were separated into four groups: control for 10 weeks (C10), control for 14 weeks (C14), moderate interval training for 10 weeks (IT) and moderate continuous training for 14 weeks (CT). Rats were exercised 1 h/day, 5 day/week. Body composition and BMD of the whole body and femur respectively were assessed by dual-energy X-ray absorptiometry at baseline and after training to determine raw gain and weight-normalized BMD gain. Both trained groups had lower weight and fat mass gain when compared to controls. Both trained groups gained more BMD compared to controls when normalized to body weight. Using a 30% shorter training period, the IT group showed more than 20% higher whole body and femur BMD gains compared to the CT. Our data suggest that moderate IT was able to produce faster bone adaptations than moderate CT., (© 2016 The Authors. International Journal of Experimental Pathology © 2016 International Journal of Experimental Pathology.)

Purpose: To assess the prevalence of adverse drug reactions (ADRs) occurring in patients with Alzheimer's disease (AD) or other dementia in France., Methods: A cross-sectional multicentre study was conducted by the French network of the 31 regional pharmacovigilance centres on a given day. The subjects were selected by random draw to be a representative sample of French patients with dementia: consultations of dementia clinics, nursing-homes, acute and long care geriatric units, rehabilitation care geriatric units. The staff of each medical structure together with that of the pharmacovigilance centre defined a day for including the patients. Socio-demographic data, history, ADR and drugs given were registered., Results: There were 1332 subjects included, 51.1% living at home, 48.8% in institutions, aged 82.0 ± 8.0 years (46-108); 61.3% suffered from AD. Mean number of drugs was 6.3 ± 3.1. Anti-dementia drugs were given to 66.4% subjects. ADR prevalence was 5.0% (95% CI: 3.9-6.2) without a significant difference between at home and institutionalized patients. ADR consisted of gastro-intestinal (23.2%), central nervous system (17.4%) and psychiatric disorders (8.7%). Of the ADR, 31.9% were serious, and 47.8% preventable. The drugs most often involved were anti-dementia (28.9%), cardio-vascular (28.9%) and psychotropic drugs (26.4%, anxiolytics, hypnotics, antidepressants, neuroleptics)., Conclusion: This national scale study showed that iatrogenesis in patients with AD and related dementia can at times be serious and preventable. Therefore, special attention is required when prescribing psychotropic and anti-dementia drugs, as they are frequently used and induce half of the ADR in this population., (Copyright © 2013 John Wiley & Sons, Ltd.)

Background: Selenium is an essential element which can be toxic if ingested in excessive quantities. The main human exposure is food. In addition, intake may be boosted by consumption drinking water containing unusual high selenium concentration., Objective: We measured the individual selenium level of people exposed to selenium concentration in drinking water greater than the maximum recommended limit which is 10 μg/L., Methods: We carried out a prospective cohort study on 80 adults (40 exposed subjects i.e. living in the involved area and 40 non-exposed ones i.e. living elsewhere) in western France. We used three different approaches: (1) direct measurement of ingested selenium by the duplicate portion method, (2) dietary reconstitution with a food frequency questionnaire (FFQ) and (3) evaluation of the individual selenium status by measuring the selenium content in toenail clippings. Analyses were performed by inductively coupled plasma-mass spectrometry. The association between toenail selenium concentration and area of residence was analyzed using linear regression with repeated measurements., Results: We estimated selenium intake from FFQ at 64±14 μg/day for exposed subjects as opposed to 52±14 μg/day for the non-exposed ones. On the basis of 305 duplicate diet samples, average intake was estimated at 64±26 μg/day for exposed subjects. Area of residence (p=0.0030) and smoking (p=0.0054) were independently associated with toenail selenium concentration., Conclusion: Whatever method used for estimating selenium intake, the selenium level in this studied area with high selenium concentrated drinking water is much lower than in seleniferous areas., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

The double-stranded RNA-dependent protein kinase (PKR) is switched on by a wide range of stimuli, including the amyloid peptide. Then, PKR transmits signals to the translational machinery, apoptosis and inflammatory signaling pathways by interacting with some adapters. In virus-infected cells, PKR engages the nucleus factor κB (NF-κB) pathway. In many models of Alzheimer's disease (AD) and patients with AD, PKR was activated. Furthermore, there is strong evidence implicating the inflammatory process in the AD brain. However, the PKR involvement in inflammatory responses in AD is not elucidated. Based on our previous in vitro results, the aim of this study was to evaluate the effects of a pharmacological inhibition of PKR in inflammation in APPswePS1dE9 transgenic mice. Our results showed that PKR inhibition prevented the NF-κB activation and production of tumor necrosis factor alpha (TNFα) and interleukin (IL)-1β at 12 months of age without decrease of Aβ42 levels and memory deficits. Surprisingly, PKR inhibition failed to prevent IL-1β- mediated inflammation and induced a great increase in β-amyloid peptide (Aβ42) levels at 18 months of age. In this model, our findings highlight the lack of relationship between inflammation and Aβ42 levels. Moreover, the age-dependent inflammatory response must be carefully taken into account in the establishment of an anti-inflammatory therapy in AD.

Chronic alcohol consumption may be deleterious for bone tissue depending on the amount of ethanol consumed, whereas physical activity has positive effects on bone. This study was designed to analyze the effects of moderate alcohol consumption on bone in trained rats. 48 male Wistar rats were divided into four groups: control (C), alcohol (A), exercise (E) and alcohol + exercise (AE). A and AE groups drank a solution composed of water and ethanol. E and AE groups were trained for 2 months (treadmill: 40 min/day, 5 times/week). Body composition and bone mineral density (BMD) were assessed by dual X-ray absorptiometry and microarchitectural parameters using micro-computed tomography. Serum osteocalcin and CTx were determined by ELISA assays. The body weight and lean mass gain were lower in group A, while the fat mass gain was lower in exercised groups. BMD and BMC were higher with alcohol after body weight adjustment. Trabecular thickness was significantly higher in AE and A groups compared to C and E; cross-sectional area was larger in A and C groups compared to AE and E. CTx levels were higher in A compared to C and in AE and E versus C and A. Osteocalcin levels were significantly greater in AE and E groups versus C and A. In conclusion, the light to moderate alcohol consumption over a short period increased the trabecular thickness, BMC and BMD in A and AE groups. However, we observed alterations in bone remodeling and body composition with alcohol, at the end of the protocol, which did not appear when alcohol was combined to exercise.