The place of the relative at the time of the announcement of cancer progression: BABEL - a mixed-methods study.

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.

Familial colonoscopic screening: how do French general practitioners deal with patients and their high-risk relatives. A qualitative study.

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.

[Consequences of childhood cancer in the quest for first job in the Grand Ouest inter-region: A mixed-method study designed from the Grand Ouest Cancer de l'Enfant (GOCE) organization in childhood cancer survivors and professionals]. / Conséquences d'un cancer dans l'enfance dans la quête du premier emploi dans l'interrégion Grand Ouest. Étude multiméthodes du groupe Grand Ouest Cancer de l'Enfant (GOCE) chez d'anciens patients et des professionnels.

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.

Effectiveness of drugs acting on adrenergic receptors in the treatment for tobacco or alcohol use disorders: systematic review and meta-analysis.

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.

Information sur le risque familial de cancer colorectal. Regards croisés sur l'efficacité d'une intervention personnalisée.

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.

Acute Clostridioides difficile Infection in Hospitalized Persons Aged 75 and Older: 30-Day Prognosis and Risk Factors for Mortality.

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.

Serious adverse effects occurring after chemotherapy: A general cancer registry-based incidence survey.

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.

Toxicities associated with chemotherapy regimens containing a fluoropyrimidine: A real-life evaluation in France.

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.

[Family risk information for colorectal cancer. Perspectives on the effectiveness of a tailored intervention] / Information sur le risque familial de cancer colorectal. Regards croisés sur l'efficacité d'une intervention personnalisée.

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.

Positive perception of aging is a key predictor of quality-of-life in aging people.

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.

Lack of effects of simvastatin on smoking cessation in humans: A double-blind, randomized, placebo-controlled clinical study.

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.

Tolerance of subcutaneously administered antibiotics: a French national prospective study.

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 [19­104] 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.

Colonoscopy uptake for high-risk individuals with a family history of colorectal neoplasia: A multicenter, randomized trial of tailored counseling versus standard information.

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.

Health-related quality of life after laparoscopic sleeve gastrectomy. A multicentric experience.

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.

Quick benefits of interval training versus continuous training on bone: a dual-energy X-ray absorptiometry comparative study.

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.

Adverse drug reactions in patients with Alzheimer's disease and related dementia in France: a national multicentre cross-sectional study.

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.

The validation of a French-language version of the Aging Perceptions Questionnaire (APQ) and its extension to a population aged 55 and over.

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 = 94), 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.

Pharmacological inhibition of PKR in APPswePS1dE9 mice transiently prevents inflammation at 12 months of age but increases Aß42 levels in the late stages of the Alzheimer's disease.

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)-1ß at 12 months of age without decrease of Aß42 levels and memory deficits. Surprisingly, PKR inhibition failed to prevent IL-1ß- mediated inflammation and induced a great increase in ß-amyloid peptide (Aß42) levels at 18 months of age. In this model, our findings highlight the lack of relationship between inflammation and Aß42 levels. Moreover, the age-dependent inflammatory response must be carefully taken into account in the establishment of an anti-inflammatory therapy in AD.