NFL strongly correlates with TNF-R1 in the plasma of AD patients, but not with cognitive decline.

Peripheral inflammation mechanisms involved in Alzheimer's disease (AD) have yet to be accurately characterized and the identification of blood biomarker profiles could help predict cognitive decline and optimize patient care. Blood biomarkers described to date have failed to provide a consensus signature, which is mainly due to the heterogeneity of the methods used or the cohort. The present work aims to describe the potential informativity of peripheral inflammation in AD, focusing in particular on the potential association between the level of plasma neurofilament light (NFL), peripheral inflammation (by quantifying IL-1ß, IL-6, TNFα, CCL5, TNF-R1, sIL-6R, TIMP-1, IL-8 in blood) and cognitive decline (assessed by the MMSE and ADAScog scales) through a 2-year follow-up of 40 AD patients from the Cytocogma cohort (CHU Poitiers, Pr M. Paccalin). Our results show for the first time a strong correlation between plasma NFL and TNF-R1 at each time of follow-up (baseline, 12 and 24 months), thus opening an interesting perspective for the prognosis of AD patients.

Determinants of doctors' antibiotic prescriptions for patients over 75 years old in the terminal stage of palliative care.

INTRODUCTION: Notwithstanding high prevalence of presumably bacterial infections in elderly persons (EP) in palliative care (PC), there exists no recommendation on the role of antibiotic therapy (ABP) in this type of situation. OBJECTIVE: To describe the determinants of antibiotic prescription by general practitioners (GP) and by doctors practicing in institutions (DPI) for patients>75 years, in end-of-life situations in PC. METHOD: Descriptive investigation by anonymous self-administered questionnaire disseminated in France by e-mail. RESULTS: A total of 301 questionnaires analyzed: 113 GP, 188 DPIs. The latter were mainly geriatricians (69, 36.6%) and infectologists/internists (41, 21.8%). Sixty-three (55,75%) GPs and 144 (78.7%) DPIs stated that they had prescribed antibiotics. Practice in "EHPAD" retirement homes or intensive care was often associated with non-prescription of antibiotics. Age, PC training and number of patients monitored bore no influence. Family involvement in decision-making was more frequent for GPs than for DPIs. The main purpose of antibiotic therapy was to relieve different symptoms (fever, respiratory congestion, functional urinary signs). Most of the doctors (81%) had previously encountered complications (allergy, adverse effect), which represented the main causes of treatment discontinuation. CONCLUSION: Antibiotic use in end-of-life EPs in PC seems frequent. In accordance with the principle of beneficence, its goal of often symptom-related; that said, in the absence of scientific data, antibiotic prescription in end-of-life situations should be individualized in view of observing the other ethical caregiving principles (beneficence, non-maleficence, justice, patient autonomy) and re-evaluated daily.

Comprehensive geriatric assessment in older patients suffering from infective endocarditis. A prospective multicentric cohort study.

OBJECTIVES: The aim was to describe the impact of infective endocarditis (IE) on functional, cognitive and nutritional statuses, and to estimate the influence of these parameters on surgical management and mortality. METHOD: This was a prospective study over 13 months in 14 French hospitals, including patients ≥75 years of age with definite or possible IE. A comprehensive geriatric assessment (CGA) was performed during the first week of hospitalization, including a retrospective estimation of functional status 2 months before hospitalization, and 3 months after. RESULTS: A total of 120 patients were included (mean age 83.1 ± 5.0 (75-101) years). IE was associated with a dramatic impairment of functional status between 2 months prior hospitalization and the first geriatric evaluation (90.8% able to walk vs. 35.5% (p < 0.0001), ADL (Activities in Daily Living) 5.0 ± 1.7 vs. 3.1 ± 2.1 (p < 0.0001)). The 19 operated patients (15.8%) had less comorbidities (cumulative illness rating scale geriatric 10.8 ± 8.2 vs. 15.3 ± 7.1 (p 0.0176)), better functional (ADL 5.9 ± 0.4 vs. 4.9 ± 1.8 (p 0.0171) and nutritional (mini nutritional assessment 20.4 ± 5.0 vs. 17.3 ± 6.2 (p 0.0501)) statuses than non-operated patients. Among all infectious, cardiac and geriatric parameters, body mass index (HR 0.9, range 0.8-1, p 0.05) and ADL at the time of the first evaluation (HR 0.7, range 0.6-0.9, p 0.002) were the sole independent predictors of the 3-month (32.5%) and 1-year mortality (42.5%). Three months later, the 57 assessed patients only partially recovered their ADL (3.7 ± 1.9 vs. 5.3 ± 1.4 2 months prior hospitalization and 4.6 ± 1.9 at the first CGA; p < 0.0001). CONCLUSION: Functional and nutritional abilities are crucial components that can be accurately explored through a CGA when managing IE in oldest patients.

Treatment compliance with European guidelines and prognosis of Clostridium difficile infection according to age.

OBJECTIVE: Age>65 years is associated with the recurrence and poor prognosis of Clostridium difficile infection (CDI). Data on elderly patients (≥75 years) is scarce, and little is known about compliance with European guidelines in terms of specific treatment. We aimed to analyze the treatment and prognosis of CDI in two groups of patients aged

Subcutaneously administered antibiotics: a national survey of current practice from the French Infectious Diseases (SPILF) and Geriatric Medicine (SFGG) society networks.

A national survey was performed to explore antibiotic prescription by the subcutaneous (sc) route among French infectious diseases and geriatric practitioners. Among the participating physicians, 367 (96.1%) declared administering sc antibiotics at some point. Ceftriaxone was prescribed sc by all but one, and ertapenem, teicoplanin, aminoglycosides and amoxicillin by 33.2%, 39.2%, 35.1% and 15.3%, respectively. The sc route was resorted to mainly in case of unavailable oral, intravenous or intramuscular routes, especially during palliative care. Pain, skin necrosis and lack of efficacy were the main adverse effects, reported by 70.8%, 12.8% and 19.9% of practitioners, respectively. Further studies are needed to precise the indications, modalities and tolerance of sc antibiotic use.

Neuroinflammation and ß amyloid deposition in Alzheimer's disease: in vivo quantification with molecular imaging.

BACKGROUND/AIMS: Neuroinflammation plays a crucial role in the pathogenesis of Alzheimer's disease (AD). Its relationship with underlying ß amyloid deposition remains unclear. In vivo visualization of microglial activation has become possible with the development of molecular imaging ligands when used with positron emission tomography (PET). The translocator protein (TSPO) is upregulated during neuroinflammation. Consequently, targeting TSPO with radiolabeled ligands for PET is an attractive biomarker for neuroinflammation. METHODS: A review of the research literature on PET imaging which studied in vivo neuroinflammation in AD subjects and its relationship with amyloid load was performed, including papers published between 2001 and 2012. RESULTS: Six studies were included using either [(11)C]PK-11195 or another non-TSPO radioligand that binds to the monoaminooxidase B. All the studies evaluated amyloid load with [(11)C]PIB. Microglial activation and astrocytosis are potentially early phenomena in AD. However, the individual levels of amyloid deposition and microglial activation were not correlated. CONCLUSION: Noninvasive in vivo molecular imaging to visualize neuroinflammation in AD may contribute to our understanding of the kinetics of neuroinflammation and its relationship to the hallmarks of the disease. Both are important for the development of future therapeutic modalities and for quantifying the efficacy of future disease-modifying treatments.

Diagnostic criteria for urinary tract infection in hospitalized elderly patients over 75 years of age: a multicenter cross-sectional study.

INTRODUCTION: Urinary tract infection (UTI) is one of the most frequent infections in geriatric patients. Nevertheless, the diagnosis remains difficult because of the high prevalence of asymptomatic bacteriuria (AB). We studied the diagnosis criteria used by physicians in geriatric patients 75 years of age or more. METHOD: A multicenter study was carried out in October 2009 in acute care wards (geriatrics, infectious diseases, internal medicine). During 1 week, the local investigator collected all positive urine microscopy and culture in geriatric patients 75 years of age or more and filled out a questionnaire on the final diagnosis (AB, cystitis, pyelonephritis, prostatitis), symptoms, clinical signs, and other infectious diagnosis. RESULTS: Two hundred and forty-one questionnaires were filled out in 48 wards. Physicians diagnosed AB in 91 patients (37.8%), cystitis in 72 (29.9%), pyelonephritis in 48 (19.9%), prostatitis in 20 (8.3%). 28.2% of patients were asymptomatic; 35% presented with clinical signs. General signs were significantly associated with invasive infection and the absence of functional signs with AB. Among the patients presenting with an invasive UTI, 27.9% also presented with another infection. This other infection was not statistically associated with AB, cystitis, or invasive UTI. CONCLUSION: Too many urine microscopy and culture procedures are not justified, and too many patients are diagnosed with several infections. Usual functional and clinical signs are important for the diagnosis but are infrequent. It seems necessary to review the range of clinical presentations and diagnostic criteria for UTI in geriatric patients.

Survey of vaccination policies in French healthcare institutions.

OBJECTIVE: The survey was implemented to describe vaccination policies for healthcare professionals in French healthcare institutions. METHODS: A cross-sectional survey based on questionnaires was sent to occupational physicians and chairpersons of hospital infection prevention and control committees (HIPC) of 38 institutions between November 2010 and January 2011. RESULTS: Twenty-nine occupational physicians and 26 hospital infection prevention and control committees chairpersons (HIPC), from 30 institutions answered (response rate: 79%), 70% of the institutions were university hospitals. Overall, 76% of occupational physicians and 85% of HIPC chairpersons reported that information and awareness campaigns about vaccination recommendations for healthcare professionals were usually conducted in their establishment. Fifty-nine percent of occupational physicians and 31% of HIPC chairpersons reported that they were aware of the vaccine coverage rates of professionals in their institution. The occupational physicians reported that they suggested diphtheria, tetanus, polio, influenza, and acellular pertussis vaccination to all staff at their annual visit in 100%, 97%, and 62% of cases, respectively. Varicella and measles vaccinations were never suggested in 31% and 17% of cases, respectively. Among respondents, 55% of physicians reported that they had already managed a pertussis epidemic, and 42% a measles epidemic, and in both of these cases an awareness campaigns were usually conducted (93% and 96%). CONCLUSIONS: The vaccine coverage rates of healthcare professionals in French healthcare institutions remain insufficiently documented and could be improved.

Prevention of the ß-amyloid peptide-induced inflammatory process by inhibition of double-stranded RNA-dependent protein kinase in primary murine mixed co-cultures.

BACKGROUND: Inflammation may be involved in the pathogenesis of Alzheimer's disease (AD). There has been little success with anti-inflammatory drugs in AD, while the promise of anti-inflammatory treatment is more evident in experimental models. A new anti-inflammatory strategy requires a better understanding of molecular mechanisms. Among the plethora of signaling pathways activated by ß-amyloid (Aß) peptides, the nuclear factor-kappa B (NF-κB) pathway could be an interesting target. In virus-infected cells, double-stranded RNA-dependent protein kinase (PKR) controls the NF-κB signaling pathway. It is well-known that PKR is activated in AD. This led us to study the effect of a specific inhibitor of PKR on the Aß42-induced inflammatory response in primary mixed murine co-cultures, allowing interactions between neurons, astrocytes and microglia. METHODS: Primary mixed murine co-cultures were prepared in three steps: a primary culture of astrocytes and microglia for 14 days, then a primary culture of neurons and astrocytes which were cultured with microglia purified from the first culture. Before exposure to Aß neurotoxicity (72 h), co-cultures were treated with compound C16, a specific inhibitor of PKR. Levels of tumor necrosis factor-α (TNFα), interleukin (IL)-1ß, and IL-6 were assessed by ELISA. Levels of PT451-PKR and activation of IκB, NF-κB and caspase-3 were assessed by western blotting. Apoptosis was also followed using annexin V-FITC immunostaining kit. Subcellular distribution of PT451-PKR was assessed by confocal immunofluorescence and morphological structure of cells by scanning electron microscopy. Data were analysed using one-way ANOVA followed by a Newman-Keuls' post hoc test RESULTS: In these co-cultures, PKR inhibition prevented Aß42-induced activation of IκB and NF-κB, strongly decreased production and release of tumor necrosis factor (TNFα) and interleukin (IL)-1ß, and limited apoptosis. CONCLUSION: In spite of the complexity of the innate immune response, PKR inhibition could be an interesting anti-inflammatory strategy in AD.

Images in gerontology: a case report.

Left ventricular aneurysm can complicate acute myocardial infarction. Clinical and electrocardiogram features are not specific. We describe a case with asymptomatic left ventricular aneurysm diagnosed by computerized-tomography angiography.

[Transfusion in clinical practice in geriatric wards]. / Enquête transversale sur la transfusion dans les services de gériatrie.

PURPOSE: In the absence of specific recommendations on blood transfusion in elderly subjects, we carried out a survey to assess transfusion practices in geriatric medicine. METHODS: A descriptive, national, cross-sectional survey was conducted in 14 French geriatric departments (12 teaching hospitals and two general hospitals). In each department, five patients receiving transfusions were randomly selected in order to analyze their characteristics, the indications of blood transfusion, the criteria for and the methods of transfusion compared with Afssaps recommendations on transfusion thresholds. RESULTS: Data were analyzed for 70 patients (mean age 86+/-7 years, sex ratio female to male 1.8, with an average of five+/-two pathologies and six+/-three treatments). The indicators of poor tolerance included confusion (23 %), somnolence (22 %), acute heart failure (17 %) or coronary heart disease (16 %), and differed from the Afssaps criteria in the majority of cases. The transfusion threshold that were considered in the absence of poor tolerance (45 % of transfusions) differed from that recommended by Afssaps in 26 % of cases. The main adverse event in transfusion recipients was heart failure. CONCLUSION: When criteria for poor anaemia tolerance or transfusion thresholds are considered, transfusion practices in geriatric subjects have specific features. Further studies are needed to validate the appropriateness of the practices described in this survey.

[Impact of routine pediatric varicella vaccination on the epidemiology of herpes zoster]. / Impact de la vaccination de routine de l'enfant contre la varicelle sur l'épidémiologie du zona.

OBJECTIVE: This literature review addresses the following question: what elements point to an impact of routine chicken pox vaccination of children on the incidence of shingles? DESIGN: The search strategy involved an electronic search (Medline database via PubMed) and crossed references. Articles were selected by reading their abstracts. RESULTS: There were few published studies dealing with the question. A total of 13 publications reported seven longitudinal studies on the incidence of shingles and six mathematical models. The population studies were all American, and reported discordant results, four reporting an increase, and three, stability in the incidence of shingles. Four of the six mathematical models concerned the impact of routine chicken pox vaccination on shingles epidemiology. All showed a transitory short-term increase in the incidence of shingles (on condition that vaccine was effective and coverage high) and a long-term incidence of shingles lower than the current rate. CONCLUSIONS: The currently available data is insufficient for any conclusion to be drawn as to the impact of routine pediatric chicken pox vaccination on the incidence of shingles. Monitoring the incidence of shingles in countries either recommending or not such vaccination should be maintained.

[Vaccine coverage against influenza and pneumococcal infections in patients aged 65 and over: a survey on 299 outpatients]. / Couverture vaccinale antigrippale et antipneumococcique à partir de 65ans : étude sur 299 patients ambulatoires.

INTRODUCTION: There is no compulsory vaccination in the adult population. Therefore, vaccine coverage appears heterogeneous. METHODS: We performed a 2-month survey to evaluate the vaccine coverage administered by 11 general practitioners in their patients aged 65 and over, with a focus on influenza vaccination recommended in France for individuals being 65 years old or more and on pneumococcal vaccination indicated but not recommended in the same age population; analysing the reasons for non vaccine administration against influenza and pneumococcal infections. RESULTS: Two hundred and ninety-nine patients were interviewed, mean age of 77+/-6,9 years; 76,3% were vaccinated against influenza; only nine patients out of the 46 having a recommendation for pneumococcal vaccine were immunized (19,6%). The main reasons for non vaccination were the fear of vaccine for influenza and a lack of information for the pneumococcal vaccine. CONCLUSION: These results underline the low prevalence for pneumococcal vaccine in ambulatory patients, despite recommendations. Previous studies with controversial data might explain the low prevalence. Better information of the expected benefit of this vaccine and better correlation between indications and recommendations could increase its coverage.

[Late diagnosis of Dandy-Walker syndrome revealed by gait disorders in an elderly]. / Diagnostic tardif d'un syndrome de Dandy-Walker révélé par des troubles de la marche chez le sujet âgé.

The Dandy-Walker syndrome is a rare malformation usually diagnosed during pregnancy or early in the course of life. We report a case in an elderly hospitalised for gait disorders and recurrent falls. Cerebral MRI revealed hydrocephalus and posterior fossa cyst. The patient improved after ventriculocisternostomia.

[Diagnosis and epidemiological surveillance of influenza and respiratory syncytial virus infections: interest of multiplex PCR]. / Diagnostic et surveillance épidémiologique des infections grippales et à virus respiratoire syncytial: intérêt de la PCR multiplex.

OBJECTIVE: Respiratory infections require a rapid etiological diagnosis for efficient management of cases. We evaluated multiplex PCR used for the diagnosis and the epidemiological surveillance of influenza and respiratory syncytial virus (RSV) infections. PATIENTS AND METHODS: Our study included 278 patients (mean age: 37.2+/-22.9 years) with flu or flu-like syndromes, consulting physicians affiliated with the GROG Poitou-Charentes or hospitalized in the Poitiers teaching hospital. A multiplex PCR detecting A(H3), A(H1) and B influenza viruses, and RSV A and B, was performed with both a direct examination by immunofluorescence and cell-culture. RESULTS: We diagnosed a viral infection in 139 (50.0%) patients: 99 cases of influenza A(H3), 2 cases of influenza A(H1), 28 cases of influenza B and 11 cases of RSV infections. The diagnosis yield in GROG patients (52.3%) was significantly higher than that observed in hospitalized patients (34.5%) (P=0.04). All techniques were correlated in 61% of cases. The multiplex PCR yielded 22.3% more positive samples compared to the conventional techniques. All positive samples by conventional techniques were also positive by multiplex PCR. We observed a perfect correlation between viral types and subtypes determined by PCR and cell-culture. CONCLUSION: Multiplex PCR is a sensitive technique allowing an efficient and rapid diagnosis of respiratory infections due to influenza and RSV.

[Identification errors and delusions of false identification in Alzheimer's disease: a regional survey]. / Troubles de l'identification et délires d'identité dans la maladie d'Alzheimer: une enquête régionale.

INTRODUCTION: Misidentification syndromes are the main symptoms in Alzheimer's disease. Underlain by complex cognitive, agnosic, and amnesic disturbances of degenerative etiology, they can be expressed by misidentification delusions, as in psychoses. To date, research has focused on identification disturbances of persons selected according to various definitions. OBJECTIVE: Our main objective was to evaluate the frequency of identification disturbances among patients suffering from Alzheimer's disease within the current conditions of diagnosis and treatment. The secondary objective aimed to establish a detailed analysis of symptoms and clinical correlations, and evaluate the effects of the troubles on the caregiver. METHODS: We conducted a regional survey using a questionnaire designed for the caregiver, proposed to the 60 geriatric doctors and neurologists in the Poitou-Charentes region of France, for all patients suffering from Alzheimer's disease (defined according to DSM IV criteria) seen between June 1st and August 31st of 2003. Statview software was used for statistical analysis. RESULTS: The survey was completed for 104 patients: 69.5 percent women and 30.5 percent men, with a mean age of 79 years. The majority of the patients were seen by a neurologist and presented an average cognitive deficiency (MMS ranging from 11 to 20). An identification disturbance, whether or not it was delusional, all domains included, was found in 81.6 percent of the patients and was related to a more severe cognitive deficiency and greater hardship on the part of the caregiver. DISCUSSION: We observed a high prevalence of identification disturbance, which can be explained by the systematic and exhaustive search for identification disturbance. The most frequent disturbance concerned the identification of places, whereas self-identification was less often affected; the authentic Capgras delusion was found less often. CONCLUSION: The study of identification disturbances in Alzheimer's disease can contribute to a better understanding of the cognitive, psychopathological, and physiopathological aspects of the disease as well as to a better knowledge and better care for the patient.

Antiphospholipid syndrome in patients with retinal venous occlusion.

INTRODUCTION: We conducted a prospective study to determine the prevalence and the prognosis of antiphospholipid syndrome (APS) in patients with retinal venous occlusion (RVO). PATIENTS: Consecutive patients presenting with retinal vein occlusion were screened for vascular risk factors (diabetes mellitus, hypertension, hyperlipidemia) and for antiphospholipid antibodies (aPL): anticardiolipin (aCL), anti-beta2-glycoprotein I, and lupus anticoagulant. Patients with a serum sample positive for aPL returned at least 6 weeks later for a new screening to determine the prevalence of antiphospholipid syndrome. All patients were followed to determine the outcome. RESULTS: Sixty-eight patients presented with RVO, 16 had vascular risk factors for RVO. After two screenings for aPL, nine cases of antiphospholipid syndrome associated with RVO were diagnosed (13.2%). Eight patients were over age 50 years and none had a previous thrombotic event before RVO. All patients were treated with aspirin (160 mg/day). With a mean follow-up of 26.1+/-8.2 months (range, 16-36 months), there were no recurrences. CONCLUSION: Retinal venous occlusion is multifactorial in origin. In patients aged 50 years and older, without previous thrombotic event, aPL might not be predictive of recurrences and treatment with aspirin might be sufficient. In such patients, the routine screening for aPL does not appear warranted, but a randomized study should be conducted to really ascertain the pathogenic role of aPL and the most appropriate treatment in RVO.