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The present work examined the hypothesis that brain ischemic tolerance induced by ischemic preconditioning (IPC) is triggered by an initial oxidative stress and is associated with an increase in antioxidant enzyme activities as one end-effector of the neuroprotection. Wistar rats were preconditioned by a single 3-min occlusion of the middle cerebral artery. After a various duration of reperfusion (30 min, 24, 72 or 168 h), rats were subjected to a 60-min focal ischemia and sacrificed 24 h later. Cerebral infarcts were significantly reduced when performed during the 24- to 72-h time window after IPC. The pretreatment with the protein synthesis inhibitor, cycloheximide (1 mg/kg, i.p., 30 min prior to IPC), completely suppressed the neuroprotection. The free radical scavenger, dimethylthiourea (DMTU; 300 mg/kg, i.p., 30 min prior to IPC) and the antioxidant ebselen (10 mg/kg, oral cramming, 2 h before and 12 h after IPC) also abolished the IPC-induced protection of the brain. Nevertheless, IPC did not induce any delayed changes in antioxidant enzyme (superoxide dismutase, glutathion peroxidase) activities nor in the neuronal expression of Mn and Cu/Zn superoxide dismutase. These results indicate that an initial oxidative stress could be involved as a trigger of IPC, while antioxidant enzymes do not play a key role as end-effectors in such a neuroprotection. [Copyright &y& Elsevier]

Comfort care for a dying patient increases the quality of the end of life. End-of-life situations are frequently managed in acute geriatric units (AGUs), and transition to comfort care only is often necessary. However, the frequency of transition to comfort care and the latter's putative link with the end-of-life trajectory (sudden death, cancer, organ failure, and frailty with or without dementia) have not previously been studied in acute geriatric units. We sought to (1) describe end-of-life trajectories and the transition to comfort care only, and (2) analyse the relationship between the two, prior to death in an AGU. A secondary analysis of a subgroup of the DAMAGE cohort (a prospective multicentre cohort of 3509 patients aged 75 years and over and admitted consecutively to an AGU). DAMAGE patients who died in an AGU after a stay of at least 48 hours. Data on the end-of-life trajectory and the transition to comfort care only were extracted from medical records. Of the 177 included patients, 123 (69.5%) transitioned to comfort care only in the AGU. A frailty trajectory (in patients living with dementia or not) accounted for nearly 70% of deaths. Paradoxically, only frailty among people living without dementia was not significantly associated with a more frequent transition to comfort care [odds ratio (95% confidence interval): 1.44 (0.44–4.76), relative to a patient dying suddenly]. Transition to comfort care only is frequent in AGUs and is linked to the end-of-life trajectory (except for frail patients living without dementia). The frailty trajectory is one of the most frequent, and, therefore, physicians must be aware of the need to improve practice in this context. [ABSTRACT FROM AUTHOR]

Building a prediction model based on both real data and expert knowledge can be challenging. We experienced this difficulty in our context of predicting fall risk factors in the elderly, where two sources of data were available: hand-reported information from medical consultations and expert information from human specialists. As is often the case, the real data were incomplete and imbalanced, and the participation of medical experts required the selection of a kind of model they can understand. This article describes the steps followed in the construction and evaluation of the model, structured as a new framework. The proposed model is a Bayesian network (BN) built from expert knowledge and learning from a real data set, guided by both the understandability of the BN graph and the performance of the model to predict risk factors. The resulting Bayesian network model includes 90 variables to evaluate 10 actionable target risk factors. It demonstrated its potential compared to other classifiers in terms of prediction performance, whilst offering a higher degree of interpretability. • Build a Bayesian Network (BN) by combining expert knowledge and a real data set. • Propose a complete framework to build an efficient and understandable BN model. • Propose a knowledge model including 90 variables and 10 target risk factors for fall. • Predict 10 risk factors for fall and compare with usual classifiers. • Improve the understandability of the BN model thanks to local graphical models. [ABSTRACT FROM AUTHOR]

Objectives. To evaluate spinal curvature changes over a 3-year period in postmenopausal women who had had an osteoporotic vertebral fracture within the last 3 months. Methods. Thoracic kyphosis and lumbar lordosis were measured using a curviscope at baseline and after 1, 3, 6, 12, and 36 months. Anteroposterior and lateral radiographs of the thoracolumbar spine were obtained after 1 and 3 years. Results. Sixty-one patients were included. At baseline, a significant increase in thoracic curvature was found in the subgroup with thoracic fractures as compared to the subgroups with thoracolumbar or lumbar fractures (64° ± 9°, 56° ± 10 , and 56° ± 13 , respectively; P < 0.05). No lumbar curvature differences were found. Thoracic curvature was significantly correlated with age (r= -0.48, P<0.001) and with the vertebral deformity index (r = 0.6, P < 0.001). A significant increase in thoracic curvature was apparent 3 months into the study; after 3 years, the increase was 5.6° ± 0.7  (P < 0.01). A moderate increase in lumbar curvature was found after 3 years (P < 0.01). Five of 13 patients and five of 10 patients had at least one incident fracture after 1 and 3 years, respectively. Mean thoracic curvature was greater among the patients with than without incident fractures after 1 and 3 years, although the difference was not statistically significant. Conclusion. Thoracic compression fractures significantly increase thoracic kyphosis as compared to dorsolumbar and lumbar fractures. Thoracic kyphosis worsens over time in patients with prevalent vertebral fractures. These data invite an evaluation of techniques capable of providing early correction of alignment disorders, such as widespread use of bracing or kyphoplasty. [Copyright &y& Elsevier]

During aging, individuals can be classified as being in one of 3 different states: robust, frail or dependent. Frailty is described as reversible, so early detection offers the potential of returning the subject to a robust status. There are multiple clinical frailty scales but no gold standard and frailty is not systematically assessed in clinicians' daily practice. Reliable biomarkers of frailty are lacking, however, while their identification and systematic use would make this simple scale a useful clinical tool. To conduct a review of the literature concerning the biomarkers associated with frailty and to compare in a meta-analysis the plasmatic values of each biomarker in the frail with the robust group. 503 articles were identified on PubMed, 467 on Scopus and 369 on Web Of Science. 67 articles were included, collecting a total of 32,934 robust subjects and 6864 frail subjects. C-reactive protein (CRP) (Standardized Mean Difference (SMD): 0.49 CI 95% [0.37–0.61]) was significantly higher in the frail group whereas hemoglobin (SMD: −0.67[−0.90; −0.44]), albumin (SMD: −0.62[−0.84; −0.41]), 25-hydroxyvitamin D (25OHD) (SMD: −0.43 [−0.64; −0.21]) and, in men, free testosterone (SMD: −0.77 [−1.05; −0.49]) were significantly lower in the frail group. We found 5 biomarkers that were associated with frailty (CRP, hemoglobin, albumin, 25OHD and free testosterone in men) belonging to multiple physiological systems. Further cohort studies are needed to verify their ability to screen for frailty. • During aging, individuals can be classified as being robust, frail or dependent • Frailty is a multidimensional syndrome caused by multiple biological dysfunctions • Reliable frailty biomarkers are lacking • Multiple biomarkers should be used to assess frailty [ABSTRACT FROM AUTHOR]

Identifying risk factors for falls can improve outcomes in older patients without cognitive decline. Yet this has not been demonstrated in older people with mild cognitive impairment (MCI). We therefore sought to better identify risk factors for falls in this particular group. The analysis was conducted on the MEMENTO cohort, which is a large, French, prospective cohort. We included older people (>65 years old) with MCI (defined from neuropsychological scores) and a Short Physical Performance Battery (SPPB) score at baseline. Fallers were defined as participants having fallen at least once during the study's 2-year follow-up period. We compared clinical, neuropsychological, and biological data at baseline in fallers vs nonfallers. Additional analyses were performed on the following subgroups: women, men, people aged ≥75 years. Of the 1416 people included in our study, 194 (13.5%) fell at least once. A bivariate analysis showed that fallers were older, predominantly women, less independent in activities of daily living, and more apathetic. Fallers performed less well in executive function, balance, and gait tests. In a multivariable analysis, only age, gender, the number of limitations in instrumental activities of daily living, and living alone were significantly associated with falls. In a multivariable analysis of the subgroup of oldest patients and of the subgroup of men, executive function was significantly worse in fallers than in nonfallers. Our results demonstrate that easily attainable risk factors can be used to identify individuals with MCI with a higher risk of falls and for whom prevention could be beneficial. Future studies are needed to further evaluate the role of mild executive dysfunction in certain subgroups, such as men and oldest patients. [ABSTRACT FROM AUTHOR]

Acrylamide (AAM) has been recently discovered in food as a Maillard reaction product. AAM and glycidamide (GA), its metabolite, have been described as probably carcinogenic to humans. It is widely established that senescence and carcinogenicity are closely related. In vitro , endothelial aging is characterized by replicative senescence in which primary cells in culture lose their ability to divide. Our objective was to assess the effects of AAM and GA on human endothelial cell senescence. Human umbilical vein endothelial cells (HUVECs) cultured in vitro were used as model. HUVECs were cultured over 3 months with AAM or GA (1, 10 or 100 μM) until growth arrest. To analyze senescence, β-galactosidase activity and telomere length of HUVECs were measured by cytometry and semi-quantitative PCR, respectively. At all tested concentrations, AAM or GA reduced cell population doubling compared to the control condition ( p < 0.001). β-galactosidase activity in endothelial cells was increased when exposed to AAM (≥10 μM) or GA (≥1 μM) ( p < 0.05). AAM (≥10 μM) or GA (100 μM) accelerated telomere shortening in HUVECs ( p < 0.05). In conclusion, in vitro chronic exposure to AAM or GA at low concentrations induces accelerated senescence. This result suggests that an exposure to AAM might contribute to endothelial aging. [ABSTRACT FROM AUTHOR]

Summary: Seizures are frequent in the elderly, but their diagnosis can be challenging. The objective of this work was to develop and validate an expert-based algorithm for the diagnosis of seizures in elderly people. A multidisciplinary group of neurologists and geriatricians developed a diagnostic algorithm using a combination of selected clinical, electroencephalographical and radiological criteria. The algorithm was validated by multicentre retrospective analysis of data of patients referred for specific symptoms and classified by the experts as epileptic patients or not. The algorithm was applied to all the patients, and the diagnosis provided by the algorithm was compared to the clinical diagnosis of the experts. Twenty-nine clinical, electroencephalographical and radiological criteria were selected for the algorithm. According to criteria combination, seizures were classified in four levels of diagnosis: certain, highly probable, possible or improbable. To validate the algorithm, the medical records of 269 elderly patients were analyzed (138 with epileptic seizures, 131 with non-epileptic manifestations). Patients were mainly referred for a transient focal deficit (40%), confusion (38%), unconsciousness (27%). The algorithm best classified certain and probable seizures versus possible and improbable seizures, with 86.2% sensitivity and 67.2% specificity. Using logistical regression, 2 simplified models were developed, the first with 13 criteria (Se 85.5%, Sp 90.1%), and the second with 7 criteria only (Se 84.8%, Sp 88.6%). In conclusion, the present study validated the use of a revised diagnostic algorithm to help diagnosis epileptic seizures in the elderly. A prospective study is planned to further validate this algorithm. [Copyright &y& Elsevier]

A Fracture Liaison Service (FLS) was set up at Lille University Hospital in 2016. The purpose of this study was to assess persistence with osteoporosis treatment in patients from the FLS over a period of 1 year, and to determine predictors of discontinuation. The study population comprised adults of both genders, aged 50 or over, admitted to Lille University Hospital between January 2016 and January 2019 for a low-trauma fracture and managed in our FLS. Outcomes included (1) persistence rate at 1 year after treatment initiation, (2) persistence rate at 2 years after treatment initiation, (3) persistence rate at 1 and 2 years after treatment initiation according to type of treatment, (4) predictors of non-persistence, and (5) reasons for discontinuing treatment over 1 year after initiation. Persistence was determined using the Kaplan–Meier method. In all, 1224 patients (≥50 years old) with a recent history of low-trauma fracture (≤12 months) were identified. Of these, 380 patients – 79.2% female; mean (SD) age 76 (11) years – were seen at the FLS. In those 380 patients, 410 fractures were found and 360 of them (87.8%) were major fractures, breaking down as follows: vertebra (44%), hip (19%), proximal humerus (10%), and pelvis (8%). Osteoporosis treatment was prescribed for 367 (96.6%) patients and 275 of them began the prescribed treatment. The following anti-osteoporosis drugs were prescribed: zoledronic acid (n=150, 54.5%), teriparatide (n=63, 22.9%), and denosumab (n=39, 14.2%). Oral bisphosphonates were prescribed for a few patients (n=23, 8.4%). Persistence with osteoporosis medication (any class) was estimated at 84.1% (95% CI: 79.1% to 88.1%) at 12-month follow-up, and dropped to 70.3% (95% CI: 63.7% to 75.9%) at 24 months. When drug-specific analyses were performed using the Kaplan–Meier method, persistence rates at 12 and 24 months were found to be higher with denosumab than with any other treatment. Independent predictors of non-persistence at 12 months were 'follow-up performed by a general practitioner (GP)' – Odds Ratio (OR) for GP vs. FLS = 3.68; 95% CI, 1.52 to 8.90, p=0.004 – and 'treatment with zoledronic acid' – OR for zoledronic acid vs. denosumab = 3.39; 95% CI, 1.21 to 9.50, p=0.019; OR for zoledronic acid vs. teriparatide = 8.86; 95% CI, 1.15 to 68.10, p=0.035. This study provides evidence of the success of our FLS in terms of long-term persistence with osteoporosis treatments. However, osteoporosis treatment initiation still needs to be improved. • Persistence with osteoporosis treatment is known to be poor, and persistence rates have been reported to decline to less than 50% over a 12-month period. • We provide compelling evidence of the success of FLS in improving long-term persistence with injectable osteoporosis treatments. • Persistence with osteoporosis medication (~92% injectable drugs) was estimated at 84.1% (95% CI: 79.1% to 88.1%) at 12-month follow-up. [ABSTRACT FROM AUTHOR]

Objective Post-fall syndrome (PFS) is a severe complication of falls in older adults. PFS is considered to be a medical emergency in geriatric patients, given the risk of a decompensatory “domino effect” and mortality. Unfortunately, there is currently no consensus on how to detect patients at risk of PFS. The primary objective of the present study was to profile patients suffering from PFS. The secondary objective was to study the prognosis of patients with PFS after their discharge from an aftercare and rehabilitation department (ARD). Material/Patients and methods We prospectively surveyed patients hospitalized in the geriatric ARD at Lille University Hospital (Lille, France) after a fall. Cases (i.e. patients meeting the criteria for PFS: the simultaneous presence of a postural disorder, a gait disorder and a psychobehavioural disorder) were compared with controls (i.e. patients free of PFS). Results Seventy-two patients were included (females: 74%). The median [interquartile range] age was 85.5 [81; 90]. Thirty-four patients (47%) had PFS. The symptoms most frequent significantly associated with PFS were retropulsion in stance, and anxiety about movement. Cases and controls did not differ significantly with regard to other signs (little step walking, axial akinesia, oppositional hypertonia, etc.). Patients with PFS were more likely to present with vascular dementia ( P = 0.0166) and osteoporosis ( P = 0.0458), and were less likely to be taking drugs associated with falls ( P = 0.0003). Initial functional assessments (according to both the Mini Motor Test and the Timed Up-and-Go test) showed that functional abilities were more severely impaired in the patients suffering from PFS. Nevertheless, the same functional assessment on discharge did not reveal a significant difference between the two groups. Likewise, there were no intergroup differences in mortality or institutionalization on discharge from the ARD. Discussion/Conclusion The imperative development of a precise, consensual definition of PFS is now justified by the gravity of this syndrome and the potential for functional recovery. Continuation of this ongoing study may highlight prognostic factors associated with the status of patients with PFS 6 months after discharge from the ARD. [ABSTRACT FROM AUTHOR]

Opinion/feedback Private practice-hospital patient pathways for elderly people with falls or at risk of falls: a study in Lille (northern France). About a third of the over-65 population will fall at least once a year. In France, falls are responsible for more than 9000 deaths among the over-65s and constitute a frequent reason for admission to long-stay care establishments [1] . Many different factors are involved in falls, which prompts the need for multidisciplinary assessments. For the last 15 years, Lille University Medical Centre (Lille, northern France) has been running multidisciplinary assessments at its day hospital for elderly people who have fallen or are at risk of falling. The patients’ medical, rehabilitational and retraining needs are identified during their admission to the day hospital. In 2013, the day hospital and the Lille urban area's existing private-practice care networks (e.g. physiotherapy) were completed by a number of innovative care systems: a care network for fall prevention and home-based rehabilitation (“ESPRAD Chute”), patient education workshops on falls, and a day hospital for follow-up care and geriatric retraining (“HDJ SSR Gériatrique”). The ESPRAD Chute network is based on nurse-led homecare and provides the patient with 15 home-based therapy sessions that complement surgery-based care. Patient education is based on 12 weekly sessions for elderly fallers. The HDJ SSR Gériatrie day hospital provides multidisciplinary rehabilitation for fallers or people at risk of falls and who require intensive rehabilitation and retraining. The interface between the day hospital and existing care structures enabled us to create private practice-hospital pathways for the multidisciplinary management of elderly people at risk of falls. We present our experience of these patient pathways and the associated care systems. [ABSTRACT FROM AUTHOR]