Association between dementia and reduced walking ability and 30-day mortality in patients with extended-spectrum beta-lactamase-producing Escherichia coli bacteremia.

Previous studies have shown controversial results of factors associated with short-term mortality in patients with extended-spectrum beta-lactamase (ESBL)-producing E. coli bacteremia and no research has investigated the impact of the geriatric assessment criteria on short-term mortality. Our objective was to determine whether dementia and walking ability are associated with 30-day mortality in patients with ESBL-producing E. coli bacteremia. All blood bottle cultures, analyzed from January 2008 to April 2015, in the Bacteriology Department of a 2,600-bed, university-affiliated center, Nantes, France, were retrospectively extracted. Factors associated with short-term mortality in patients with ESBL-producing E. coli bacteremia: 140 patients with an ESBL-producing E. coli bloodstream infection were included; 22 (15.7%) patients died within 30 days following the first positive blood bottle culture of ESBL-producing E.coli. In multivariate analysis, a reduced ability to walk (OR = 0.30; p = 0.021), presence of dementia (OR = 54.51; p = 0.040), a high Sepsis-related Organ Failure Assessment (SOFA) score (OR = 1.69; p < 0.001), presence of neutropenia (OR = 12.94; p = 0.049), and presence of a urinary tract infection (OR = 0.07; p = 0.036), were associated with 30-day mortality. Our findings provide new data showing an independent association between 30-day mortality with dementia and reduced walking ability, in patients with ESBL-producing E. coli bacteremia. These criteria should be considered in the therapeutic management of patients with ESBL-producing E. coli bacteremia.

Derivation and validation of a Short Form of the Mini-Mental State Examination for the screening of dementia in older adults with a memory complaint.

BACKGROUND AND PURPOSE: To validate a Short Form of the Mini-Mental State Examination (SMMSE) as a screening test for dementia in older ambulatory individuals followed in a memory clinic for a memory complaint. METHODS: A total of 202 cognitively healthy individuals, 100 individuals with a mild cognitive impairment and 304 demented individuals sent for a memory complaint by their primary care physician to a memory clinic were prospectively included in this cross-sectional study. They were randomized into derivation (n = 303) and validation (n = 303) groups. The SMMSE score was built from six memory items of MMSE, with a score ranging from 0 to 6 (i.e. best performance). RESULTS: The receiver operating characteristic curve showed an area under the curve of 0.98 for the derivation group and 0.97 for the validation group without differences between curves (P = 0.254). The cut-off between the sensitivity and the specificity of the SMMSE score for clinically diagnosed dementia was ≤4. The performance of the SMMSE for the diagnosis of dementia was high in the derivation and validation groups: sensitivity at 93.1% and 93.8%, specificity at 93.8% and 90.5%, positive predictive value at 94.3% and 90.1%, negative predictive value at 92.5% and 94.0%, likelihood ratio of positive test at 14.9 and 9.8 and of negative test at 0.07 and 0.07, respectively. CONCLUSIONS: The Short Form of the Mini-Mental State Examination was a good screening test for dementia in older individuals followed in a memory clinic for a memory complaint. The next step should be the confirmation of its discriminative value in older primary care patients.

Functional Decline in COVID-19 Older Survivors Compared to Other Pneumonia Patients, a Case Control Study.

OBJECTIVES: Among patients over 75 years, little is known about functional decline due to COVID-19. The aim of this study was to explore this functional decline, compare to other infectious pneumonia. DESIGN AND SETTING: This case-control study included all COVID-19 patients hospitalized from March to December 2020 in Acute Geriatric Ward in Nantes University Hospital matched 1/1 with patients with pneumonia hospitalized in geriatric department between March 2017 and March 2019 (controls) on sex, age. Functional decline was assessed at 3 month follow up as it is routinely done after hospitalization in geriatric ward. We performed multivariable analyses to compare clinical outcomes between patients with COVID-19 vs controls. RESULTS: 132 pairs were matched on age (mean: 87 y-o), and sex (61% of women). In multivariable logistic regression analysis, there were no statistical significant association between COVID-19 infection and functional decline (OR=0.89 p=0.72). A statistical significant association was found between functional decline and Charlson comorbidity index (OR=1.17, p=0.039); prior fall (OR=2.08, p=0.012); malnutrition (OR=1.97, p=0.018); length of hospital stay (OR=1.05, p=0.002) and preadmission ADL(OR=1.25, p=0.049). CONCLUSION: COVID-19 does not seem to be responsible for a more frequent or severe functional decline than other infectious pneumonia in older and comorbid population after 3 month follow up. In this population, pneumonia is associated with functional decline in almost 1 in 2 cases. The individual preadmission frailty seems to be a more important predictor of functional decline, encouraging multidimensional care management for this population.

Krox20 inactivation in the PNS leads to CNS/PNS boundary transgression by central glia.

CNS/PNS interfaces constitute cell boundaries, since they delimit territories with different neuronal and glial contents. Despite their potential interest in regenerative medicine, the mechanisms restricting oligodendrocytes and astrocytes to the CNS, and Schwann cells to the PNS in mammals are not known. To investigate the involvement of peripheral glia and myelin in the maintenance of the CNS/PNS boundary, we have first made use of different mouse mutants. We show that inactivation of Krox20/Egr2, a master regulatory gene for myelination in Schwann cells, results in transgression of the CNS/PNS boundary by astrocytes and oligodendrocytes and in myelination of nerve root axons by oligodendrocytes. In contrast, such migration does not occur with the Trembler(J) mutation, which prevents PNS myelination without affecting Krox20 expression. Altogether these data suggest that maintenance of the CNS/PNS boundary requires a new Krox20 function separable from myelination control. Finally, we have analyzed a human patient affected by a congenital amyelinating neuropathy, associated with the absence of the KROX20 protein in Schwann cells. In this case, the nerve roots were also invaded by oligodendrocytes and astrocytes. This indicates that transgression of the CNS/PNS boundary by central glia can occur in pathological situations in humans and suggests that the underlying mechanisms are common with the mouse.

Epstein-barr virus-infected resting memory B cells, not proliferating lymphoblasts, accumulate in the peripheral blood of immunosuppressed patients.

When Epstein-Barr virus (EBV) infects B cells in vitro, the result is a proliferating lymphoblast that expresses at least nine latent proteins. It is generally believed that these cells are rigorously controlled in vivo by cytotoxic T cells. Consistent with this, the latently infected cells in the peripheral blood of healthy carriers are not lymphoblasts. Rather, they are resting memory B cells that are probably not subject to direct immunosurveillance by cytotoxic T lymphocytes (CTLs). When patients become immunosuppressed, the viral load increases in the peripheral blood. The expansion of proliferating lymphoblasts due to the suppressed CTL response is believed to account for this increase and is considered to be a major risk factor for posttransplant lymphoproliferative disease (PTLD) and AIDS-associated B cell lymphoma. Here we show that there is an increase in the numbers of latently infected cells in the peripheral blood of immunosuppressed patients. However, the cells are not proliferating lymphoblasts. They are all latently infected, resting, memory B cells-the same population of infected cells found in the blood of healthy carriers. These results are discussed in the context of a model for EBV persistence that explains why PTLD is usually limited to the lymph nodes.

The Kaposi sarcoma-associated herpesvirus (KSHV) is present as an intact latent genome in KS tissue but replicates in the peripheral blood mononuclear cells of KS patients.

Short DNA sequences have been identified, originally in association with Kaposi's sarcoma (KS) biopsies, that are highly homologous to oncogenic, lymphotropic herpesviruses. Recently a virus, Kaposi sarcoma associated herpesvirus (KSHV) or human herpesvirus-8 (HHV-8), bearing these sequences has been identified in a cell line derived from a body cavity-based lymphoma. In this report, we show that the same sequences are present in KS biopsies as DNA molecules of a form and size characteristic of latent herpesviruses-large, covalently closed, circular episomes. The genomes migrate with an apparent size larger than the herpesvirus Epstein-Barr virus (172 kb). This form of the viral genome was found in four of four biopsies and three of five peripheral blood samples from KS patients. Linear forms of the viral genome, characteristic of viral replication, were not detected in the biopsies, but were present in the peripheral blood of three out of five patients. The sequences for KSHV/HHV-8 were also detected in the blood of four of five allograft patients and three of five healthy donors without KS suggesting that the virus is widespread throughout the human population.

[Cancer-screening for older patients]. / Dépistage des cancers chez le sujet âgé.

Cancer-screening programmes are public health action for a target population. It guarantees an equal access to screening throughout the country with a high level of quality for every person of the target population. Given the heterogeneity of older subjects and the variability of the expected benefits of cancer-screening programmes, this collective public health action may not have a collective benefit for the population. However, for older person with a life expectancy of five years or more, it would be possible to propose an individualized cancer-screening decision. This cancer-screening approach must respect the ethical principles of avoiding harm and supporting autonomy. In addition, it is important to consider the goals and values of patients to take an individualized decision. Patients with the same profile may not take the same decision of individualized cancer screening.

Validation of an integrated experimental set-up for kinetic and kinematic three-dimensional analyses in a training environment.

Biomechanical analyses using synchronized tools [electromyography (EMG), motion capture, force sensors, force platform, and digital camera] are classically performed in a laboratory environment that could influence the performance. We present a system for studying the running sprint start that synchronizes motion capture, EMG, and ground reaction force data. To maximize motion capture (Vicon 612 with six cameras), a special dim environment was created in the stadium. "Classical" tools were combined with "purpose-built" tools intended to analyse the different aspects of movement. For example, a synchronization system was built to create a common time-base for all data recordings and a portable EMG system was synchronized by a cable that was "disconnected" by the athlete's movement out of the blocks. This disconnection represented an independent event recorded by different tools. A "gap" was measured for some sprint start events between kinetic and kinematic (motion capture) data. Calibration results, measurements of time "gap", and duration of the independent event were used to validate the accuracy of motion capture and the synchronization system. The results validate the entire experimental set-up and suggest adjustment values for motion capture data. This environment can be used to study other movements and can easily be applied to several sports.

[Oral anticoagulants adherence in elderly patients treated for atrial fibrillation in the era of direct oral anticoagulants]. / Observance du traitement anticoagulant oral chez le sujet âgé à l'ère des anticoagulants oraux directs.

BACKGROUND: The aim of this study was to determine the level of adherence to oral anticoagulants in the population of elderly patients treated for a non-valvular atrial fibrillation (AF) in the era of direct oral anticoagulants. PATIENTS AND METHOD: This transversal study used Morisky scale to assess adherence to oral anticoagulants. We also collected patients' reviews about the treatment and factors explaining a poor adherence. RESULTS: Between January and June 2015, 64 patients were included in Loire Atlantique. Average age was 77.8 years, CHA2DS2-VASc score was 4.06 and treatment (vitamin K antagonists [VKAs] in 78% patients) was prescribed since 4.3 years. According to Morisky scale, 84.4% of patients had a good adherence. There was 88% of good adherence with AVK versus 71% with direct oral anticoagulant, there was no statistically significant difference. The prescriber and the knowledge of anticoagulant treatment role seemed to be determinant factors. CONCLUSIONS: The level of adherence for oral anticoagulant appears higher than in most published studies. Diversification of therapeutic options could constitute an aid to personalize the prescription in order to improve it.

Predictors of Health-Related Quality of Life Decline after Transcatheter Aortic Valve Replacement in Older Patients with Severe Aortic Stenosis.

BACKGROUND: Transcatheter aortic-valve implantation (TAVI) has been shown to improve survival and quality of life in patients with severe aortic stenosis. However, one-third of patients have poor outcome as death, functional decline or quality of life (QoL) decline. The aim of this study was to determine cardiac and geriatric predictors of physical and mental QoL decline 6 months after a TAVI procedure in patients aged 75 and older. METHODS: Between January 2013 and June 2014, we did a prospective and multicenter study including patients ≥ 75 years old referred for TAVI. The primary outcome was the measure of QoL, assessed by the Short Form 36 survey (SF-36), before and 6 months after the intervention. Association between QoL decline and baseline characteristics including cardiac and geriatric factors was analysed by logistic regression models. RESULTS: Mean age of the 150 patients studied was 83.7 years old and 56% were men. The primary end point, mean SF-36 physical summary score, significantly improved between baseline and 6-month (33.6 vs. 36.4, p=0.003) whereas mental component score significantly decreased (48.2 vs. 36.4, p-value<0.001). However, patients with presence of depressive symptoms before the intervention had mental QoL improvement at six months (OR 0.04 [0.01-0.19], p-value<0.001) and no significant geriatric predictors were associated with physical QoL decline. CONCLUSION: The mental QoL significantly decreased and patients with preoperative depressive symptoms had mental QoL improvement at six months. Researches are needed to confirm that mental QoL of patients with depressive symptoms can be improved by TAVI.

Risk of Unplanned Emergency Department Readmission after an Acute-Care Hospital Discharge among Geriatric Inpatients: Results from the Geriatric EDEN Cohort Study.

OBJECTIVES: The study aims 1) to examine whether items of the brief geriatric assessment (BGA) or their combinations predicted the risk of unplanned emergency department readmission after an acute care hospital discharge among geriatric inpatients, and 2) to determine whether BGA could be used as a prognostic tool for unplanned emergency department readmission. METHODS: A total of 312 older patients (mean age, 84.6 ± 5.4 years; 64.1% female) hospitalized in acute care wards after an emergency department visit were recruited in this observational prospective cohort study and separated into 2 groups based on the occurrence or not of an unplanned emergency department readmission during a 12-month follow-up period after their hospital discharge. A 6-item BGA was performed at emergency department admission before the discharge to acute care wards. Information on incident unplanned emergency department readmission was prospectively collected by phone call and by consulting the hospital registry. Several combinations of items of BGA identifying three levels of risk of unplanned emergency department readmission (i.e., low risk, intermediate risk and high risk) were examined. RESULTS: The unplanned emergency department readmission was more frequently associated with a temporal disorientation (P=0.004). Area under receiver operating characteristic curves of unplanned emergency department readmission based on BGA items and their combinations ranged from 0.53 to 0.61. The best predictor of unplanned emergency department readmission was the temporal disorientation (hazard ratio>1.65, P<0.035), which defined the high-risk group. Inpatients classified in high-risk group of unplanned emergency department readmission were more frequently readmitted to emergency department than those in intermediate- and low-risk groups (P log Rank <0.004). Prognostic values for unplanned emergency department readmission of items and their combinations were poor with sensitivity below 67%, specificity ranging from 36.4 to 53.7, and positive likelihood ratio below 1.4. CONCLUSIONS: The items of BGA and their combinations were significant risk factors for unplanned emergency department readmission, but their prognostic value was poor.

[Place of azathioprine in the treatment of giant cell arteritis]. / Utilisation de l'azathioprine dans le traitement de l'artérite à cellules géantes.

OBJECTIVE: The aim of this bicentric retrospective study was to describe the use of azathioprine in giant cell arteritis, and to appreciate its corticosteroid-sparing effect in glucocorticoid-dependent patients or with severe glucocorticoid related side effects. METHODS: We retrospectively reviewed the medical records of patients diagnosed with giant cell arteritis between 2000 and 2011 in two departments of internal medicine. Only the patients treated with azathioprine were included in this study. Sociodemographic, clinical, biological, radiological and therapeutic data were collected by a standardized questionnaire. A comparative analysis of daily prednisone dose at the initiation and 1 year after the prescription of azathioprine was made. RESULTS: Of the 28 patients included, 21 responded to azathioprine. At 1 year of follow-up after the initiation of azathioprine, 18 patients (64%) were still in sustained response, asymptomatic, without increase in acute phase response laboratory markers, and with a daily dose of prednisone<10 mg. Three patients (11%) experienced a relapse during azathioprine treatment. Mean daily dose of prednisone were 25.4 mg at the time of initiation of azathioprine, and 4.7 mg at 1 year of treatment, suggesting a corticosteroid-sparing effect (P<0.001). Ten patients experienced azathioprine serious side effects, leading to discontinuation of treatment in seven cases. CONCLUSION: Azathioprine may be an alternative treatment for patients with giant cell arteritis requiring prolonged high dose glucocorticoid therapy or developing severe glucocorticoid related side effects. However, given the potential adverse effects of azathioprine, a close monitoring is necessary.

[Comprehensive geriatric assessment (CGA) in elderly with cancer: For whom?]. / Évaluation gériatrique en oncologie : pour quels patients ?

Scientific societies recommend the implementation of a comprehensive geriatric assessment (CGA) in cancer patients aged 70 and older. The EGA is an interdisciplinary multidimensional diagnostic process seeking to assess the frail older person in order to develop a coordinated plan of treatment and long-term follow-up. Identification of comorbidities and age-induced physiological changes that may increase the risk of anticancer treatment toxicities is essential to better assess the risk-benefit ratio in elderly cancer patients. The systematic implementation of a CGA for each patient is difficult to perform in daily practice. Therefore, it is recommended to screen vulnerable patients who will benefit from a complete CGA. Our work presents the vulnerability screening tools validated by at least two independent studies in a cancer elderly population setting. Among seven screening tools, the G8 and the VES13 are the most effective, and have been validated specifically in older population with cancer. The G8 is recommended by scientific societies and the French National Cancer Institute (INCa) because of its easy implementation in daily clinical practice, its high sensitivity and fair specificity. Although studies are underway to improve its performance, the G8 is currently the simplest tool to routinely identify older cancer patients who should have a complete assessment in geriatric oncology.

Comparative studies of water sorption of hyaline cartilage.

Vapor phase, water sorption isotherms were obtained for specimens of bovine, sturgeon and shark cartilage and for membranes composed of collagen and various proportions of cartilage proteoglycan. The data were interpreted in the light of an elementary model for swelling of gels which regards equilibrium swelling a resultant of a balance between contractile forces of an elastic matrix and expansive forces, principally osmotic in nature. Swelling ratios for bovine and sturgeon cartilage compared at the same water vapor pressure are nearly identical, whereas the swelling ratios for shark cartilage are elevated. These high values are due principally to a higher ratio of glycosaminoglycan to collagen but also reflect a higher salt and urea content and possibly also a different type of collagen fibril network.

Conformation of hyaluronate in neutral and alkaline solutions.

Increasing the pH of a neutral salt solution of sodium hyaluronate to 12.5 produces a rapid drop in viscosity which is reversible upon restoring the pH to neutrality. Light scattering data showing a decrease in radius of gyration with no change in molecular weight and negative results with chondroitin and other acidic glycosaminoglycans suggest that the conformational change is specific for hyaluronate molecules.

General practitioners adherence to recommendations from geriatric assessments made during teleconsultations for the elderly living in nursing homes.

OBJECTIVES: To determine the factors associated with general practitioners adherence to recommendations from geriatric assessments made during teleconsultations for the elderly living in nursing homes. STUDY DESIGN: Prospective cohort study in three nursing homes in Vendee, France, with access to teleconsultations from Challans Hospital. Teleconsultations with geriatric assessment for which recommendations were made by a geriatrician (n=69). MAIN OUTCOME MEASUREMENTS: Participants were separated into two groups based on the evidence of general practitioners adherence to recommendations 30 days after teleconsultation. Their adherence has been defined by the application by themselves supporting the elderly of prescription or organization of all recommendations made by the geriatrician during the teleconsultation. The type of recommendations was pharmacological and non-pharmacological treatments, and expert medical advice. The recorded data included the main reason of teleconsultation's request, age, sex, dementia diagnosis, multimorbidities scale, body mass index, Activities of Daily Living Scale, 4-items Geriatric Depression Scale, existence of a fall, and the Neuropsychiatric Inventory. Logistic regressions were performed to examine the factors associated with general practitioners adherence to recommendations from the geriatric assessment. RESULTS: General practitioners adherence to recommendations was made for 58 teleconsultations (86.3%). A fully adjusted logistic regression showed that general practitioners adherence to recommendations was associated with risk of depressive syndrome (OR=8.00, P=0.040) and expert medical advice's recommendations (OR=17.97, P=0.040). CONCLUSIONS: General practitioners adherence to recommendations from the geriatric assessment made during teleconsultations for elderly living in nursing homes is associated with the risk of depressive syndrome's existence and the expert medical advice recommendations.

Determinants in treatment decision-making in older patients with symptomatic severe aortic stenosis.

BACKGROUND: Three treatment options are available for patients with aortic stenosis: surgical aortic valve replacement (SAVR), transcatheter aortic valve implantation (TAVI) and medical treatment (MT). However, little is known about how Heart Team treatment decisions are made under routine conditions. The aim of this study was to identify the cardiac and geriatric components associated with treatment decision-making in older patients with symptomatic severe aortic stenosis. METHODS: Between 2011 and 2013, 337 consecutive patients ≥75 years old referred for pre-operative evaluation in Nantes University Hospital had a comprehensive cardiac and geriatric assessment. In this observational retrospective study, relationships between treatment decision-making and cardiac or geriatric components were evaluated through multivariable models. RESULTS: Surgical aortic valve replacement was proposed to 108 patients, TAVI to 131 and medical treatment to 98 patients. Mean age was 83±4 years and 51% were women. Geriatric components associated with treatment decision-making between SAVR vs. TAVI were age (p<0.001, OR=0.790), comorbidity score (p=0.027, OR=0.86), functional status (p<0.001, OR=1.46), and gait speed (p<0.001, OR=0.23). Cardiac components associated with decision-making between SAVR vs. TAVI were history of previous cardiac surgery (p<0.001, OR=0.09), left ventricular ejection fraction <50% (p<0.001, OR=0.14), coronary artery disease requiring revascularization (p=0.019, OR=0.4). Between TAVI vs. medical treatment, only history of previous cardiac surgery and presence of another severe valve disease were significant. CONCLUSION: Comorbidities, functional status and physical performance, were significantly associated with the consensual treatment decision-making, independently of cardiac components in older patients with symptomatic severe aortic stenosis.

Physical function decline and degradation of postural sway dynamics in asymptomatic sedentary postmenopausal women.

BACKGROUND: Postural control is an important aspect of physical functioning. OBJECTIVE: To determine whether postural sway complexity could discriminate asymptomatic sedentary postmenopausal women with normal or subnormal physical function from those with lower physical function. DESIGN: Cross-sectional study. SETTING: Department of Geriatrics, University Hospital of Montpellier. PARTICIPANTS: 126 community-dwelling women aged 55 to 76 recruited though public meetings aimed at promoting physical activity in postmenopausal women. MEASUREMENTS: Women were asked to stand still on a force platform, either with eyes open (EO) or eyes closed (EC). Physical function was estimated using the Six-Minute Walking Distance (6MWD) test, expressed as a percentage of the predicted 6MWD (%-pred 6MWD) based on age, gender, body height, and weight. In addition to traditional stabilometric measures, dynamical measures (percentage of determinism of recurrence quantification analysis [DETRQA], sample entropy [SampEn] and complexity index of multiscale entropy [CIMSE]) were used to quantify the complexity of center of pressure (COP) time series (DETRQA: predictability, SampEn: regularity, CIMSE: multiscale regularity). RESULTS: None of the traditional stabilometric measures differentiated women with lower (%-pred 6MWD ≤ 85.5%) from those with subnormal or normal (%-pred 6MWD > 85.5%) physical function. Conversely, women with lower physical function showed lower SampEn values in the AP direction in both EO and EC conditions, as well as lower SampEn and higher DETRQA values in the ML direction in EC condition. No significant difference in the CIMSE values was found between the two groups. CONCLUSION: Lower physical function was found to be associated with lower postural sway complexity (higher regularity and predictability) in asymptomatic sedentary postmenopausal women, especially in the absence of vision. Future work is needed to determine whether a decrease in postural sway complexity could predict future decline in physical function in these women.

Limbic activation and psychophysiologic responses to aversive visual stimuli. Interaction with cognitive task.

We mapped regional brain activity and peripheral psychophysiologic responses, occurring in response to evocative emotional stimuli, and examined whether task instructions could modulate limbic activation. Ten subjects viewed pictures with neutral or aversive emotional content during simultaneous measurement of peripheral psychophysiology and brain activity with [15O]water positron emission tomography (PET). Cognitive task was manipulated by having the subjects rate the pictures or perform a recognition memory task. Aversive pictures, relative to neutral pictures, increased cerebral activity in bilateral amygdala, thalamic/hypothalamic area, midbrain, and left lateral prefrontal cortex, along with greater skin conductance responses (SCR). Voxel-by-voxel correlation coefficients between regional brain activity and SCR showed significant positive correlation peaks in the thalamus and right amygdala. Limbic activation was significantly greater during the rating condition compared to the recognition condition, suggesting that when task demands modify emotional responses, this modulation can occur at the level of limbic activity.