Search

Level of medical intervention (LMI) has to be adapted to each patient in geriatric care. LMI scales intend to help nonintensive care (NIC) decisions, giving priority to patient choice and collegial discussion. In the present study, we aimed to assess the parameters associated with the NIC decision and whether these parameters differ from those associated with in-hospital mortality. Prospective observational study. All consecutive patients from a French 62-bed acute geriatric unit over 1 year. Factors from the geriatric assessment associated with the decision of NIC were compared with those associated with in-hospital and 1-year mortality, in univariate and multivariate analyses. In total, 1654 consecutive patients (median age 87 years) were included. Collegial reflection led to NIC decision for 532 patients (32%). In-hospital and 1-year mortality were 22% and 54% in the NIC group vs 2% and 27% in the rest of the cohort (P <.001 for both). In multivariable analysis, high Charlson Comorbidity Index [odds ratio (OR) 1.15, 95% confidence interval (CI) 1.06-1.23, per point], severe neurocognitive disorders (OR 2.78, 95% CI 1.67-4.55), dependence (OR 1.92, 95% CI 1.45-2.59), and nursing home residence (OR 2.38, 95% CI 1.85-3.13) were highly associated with NIC decision but not with in-hospital mortality. Conversely, acute diseases had little impact on LMI despite their high short-term prognostic burden. Neurocognitive disorders and dependence were strongly associated with NIC decision, even though they were not significantly associated with in-hospital mortality. The decision-making process of LMI therefore seems to go beyond the notion of short-term survival. [ABSTRACT FROM AUTHOR]

Background: Immunotherapy with immune checkpoint blockers (ICB) significantly improves the prognosis for an increasing number of cancers. However, data on geriatric populations taking ICB are rare. Objective: This study aimed to identify factors associated with the efficacy and tolerance of ICB in an older population. Patients and Methods: This retrospective monocentric study included consecutive patients aged ≥ 70 years with solid cancer who received ICB between January 2018 and December 2019. Efficacy was assessed by progression-free survival (PFS) and tolerance was defined as cessation of immunotherapy due to the occurrence of any adverse event. Results: One hundred and five patients (65.7% men) were included, mainly at the metastatic stage (95.2%); 50.5% had lung cancer. Most (80%) patients were treated with anti-PD1 (nivolumab, pembrolizumab), 19.1% with anti-PD-L1 (atezolizumab, durvalumab, and avelumab) and 0.9% with anti-CTLA4 ICB (ipilimumab). Median PFS was 3.7 months [95% confidence interval (CI) (2.75–5.70)]. PFS was shorter in univariate analysis when ICB was taken concomitantly with an antiplatelet agent (AP) [hazard ratio (HR) = 1.93; 95% CI (1.22–3.04); p = 0.005]. Tolerance was lower in univariate analysis for lung cancer [odds ratio (OR) = 3.03; 95% CI (1.07–8.56), p < 0.05] and in patients taking proton pump inhibitors (PPI) [OR = 5.50; 95% CI (1.96–15.42), p < 0.001]. There was a trend toward poorer tolerance among patients living alone [OR = 2.26; 95% CI (0.76–6.72); p = 0.14]. Conclusions: In older patients taking ICB for solid cancers, concomitant AP may influence efficacy and concomitant PPI may influence tolerance. Further studies are needed to confirm these results. [ABSTRACT FROM AUTHOR]

Drug-related iatrogenesis is an important issue in the elderly population, and preventing iatrogenic accidents helps to reduce hospitalizations. Our study's objective was to evaluate prescriptions in the geriatric population of our establishment. The study conducted is a targeted clinical audit. Ten criteria were tested on the hospital prescriptions of people over 75 years old in 11 medical departments, before and after improvement actions. The non-compliance threshold was set at 10% of prescriptions for each criterion. In each phase, 165 patients were included. Four criteria were non-compliant (NC) in the first phase: the presence of Potentially Inappropriate Medications for the Elderly (PIMs) (NC = 57.6%), the adaptation of the medication to renal clearance (NC = 24.9%), the presence of illogical combination (NC = 9.7%), and the total anti-cholinergic score of the prescription (NC = 12.1%). After the implementation of improvement actions, the number of non-compliant criteria decreased between the two phases, from four to two. We obtained a significant improvement for three of the four criteria found to be non-compliant in the first phase. The criterion adaptation to renal function is close to compliance (NC = 10.1%) and the PIMs criterion remained non-compliant after reassessment (NC = 32.1%). Vigilance must be ongoing in order to limit drug iatrogeny, particularly in frail elderly patients. [ABSTRACT FROM AUTHOR]

According to the amyloid theory, the appearance of amyloid-β (Aβ) deposits represents a pivotal event in late onset Alzheimer's disease (LOAD). Physiologically, Aβ42 monomers are cleaned by capillary resorption, enzymatic catabolism, and cerebrospinal fluid (CSF) transport. Factors that promote the oligomerization of Aβ42 must be specified. In vitro, these monomers spontaneously form neurotoxic oligomers whose rate increases with time suggesting that the stasis of CSF favors the oligomerization. In animals, experimental hydrocephalus generates CSF stasis followed by the appearance of amyloid deposits. In normal pressure hydrocephalus, amyloid deposits are common, especially in elderly patients, and the turnover decline has the same order of magnitude as in AD. In this disease, the effects of CSF stasis are potentiated by the decline in the ability of CSF to inhibit the formation of oligomers. CSF originates from choroid plexus (CP). In LOAD, the functions of secretion, synthesis, and transport of CP are impaired and this is related to morphological modifications. These impairments favor the decrease of CSF turnover, the diminished levels of transthyretin, a sequestering protein synthesized by CP, and the oligomerization of Aβ42. They are potentiated by a reduced enzymatic catabolism and a decreased capillary reabsorption of Aβ42, both alterations being related to age. [ABSTRACT FROM AUTHOR]

Aging is a complex biological process which can be associated with skeletal muscle degradation leading to sarcopenia. The aim of this study consisted i) to determine the oxidative and inflammatory status of sarcopenic patients and ii) to clarify the impact of oxidative stress on myoblasts and myotubes. To this end, various biomarkers of inflammation (C-reactive protein (CRP), TNF-α, IL-6, IL-8, leukotriene B4 (LTB4)) and oxidative stress (malondialdehyde, conjugated dienes, carbonylated proteins and antioxidant enzymes: catalase, superoxide dismutase, glutathione peroxidase) as well as oxidized derivatives of cholesterol formed by cholesterol autoxidation (7-ketocholesterol, 7β-hydroxycholesterol), were analyzed. Apelin, a myokine which contributes to muscle strength, was also quantified. To this end, a case-control study was conducted to evaluate the RedOx and inflammatory status in 45 elderly subjects (23 non-sarcopenic; 22 sarcopenic) from 65 years old and higher. SARCopenia-Formular (SARC-F) and Timed Up and Go (TUG) tests were used to distinguish between sarcopenic and non-sarcopenic subjects. By using red blood cells, plasma and/or serum, we observed in sarcopenic patients an increased activity of major antioxidant enzymes (superoxide dismutase, glutathione peroxidase, catalase) associated with lipid peroxidation and protein carbonylation (increased level of malondialdehyde, conjugated dienes and carbonylated proteins). Higher levels of 7-ketocholesterol and 7β-hydroxycholesterol were also observed in the plasma of sarcopenic patients. Significant differences were only observed with 7β-hydroxycholesterol. In sarcopenic patients comparatively to non-sarcopenic subjects, significant increase of CRP, LTB4 and apelin were observed whereas similar levels of TNF-α, IL-6 and IL-8 were found. The increased plasma level of 7-ketocholesterol and 7β-hydroxycholesterol in sarcopenic patients led us to study the cytotoxic effect of these oxysterols on undifferentiated (myoblasts) and differentiated (myotubes) murine C2C12 cells. With the fluorescein diacetate and sulforhodamine 101 assays, an induction of cell death was observed both on undifferentiated and differentiated cells: the cytotoxic effects were less pronounced with 7-ketocholesterol. In addition, IL-6 secretion was never detected whatever the culture conditions, TNF-α secretion was significantly increased on undifferentiated and differentiated C2C12 cells treated with 7-ketocholesterol- and 7β-hydroxycholesterol, and IL-8 secretion was increased on differentiated cells. 7-ketocholesterol- and 7β-hydroxycholesterol-induced cell death was strongly attenuated by α-tocopherol and Pistacia lentiscus L. seed oil both on myoblasts and/or myotubes. TNF-α and/or IL-8 secretions were reduced by α-tocopherol and Pistacia lentiscus L. seed oil. Our data support the hypothesis that the enhancement of oxidative stress observed in sarcopenic patients could contribute, especially via 7β-hydroxycholesterol, to skeletal muscle atrophy and inflammation via cytotoxic effects on myoblasts and myotubes. These data bring new elements to understand the pathophysiology of sarcopenia and open new perspectives for the treatment of this frequent age-related disease. [Display omitted] • Increase of inflammatory and oxidative stress biomarkers in sarcopenic patients. • Increase of 7-ketocholesterol and 7β-hydroxycholesterol in the serum of sarcopenic patients. • 7-ketocholesterol and 7β-hydroxycholesterol induced cell death on myoblasts and myotubes (C2C12 cells). • 7-ketocholesterol and 7β-hydroxycholesterol induced inflammation on myoblasts and myotubes (C2C12 cells). • Attenuation of 7-ketocholesterol and 7β-hydroxycholesterol induced cell death and inflammation by α-tocopherol and Pistacia lentiscus L. seed oil. [ABSTRACT FROM AUTHOR]

Aim Anticholinergic drugs are widely prescribed for elderly patients and could induce several neuropsychological disorders, especially delirium. The aim of the present study was to evaluate the relationship between anticholinergic burden and delirium symptoms. Methods A total of 102 patients aged over 75 years (86.3 ± 5.8 years, 53 women and 49 men) hospitalized in a geriatric medicine department were included in this prospective study. Anticholinergic burden was assessed by classifying drug use into three levels (low, medium or high). An overall, weighted score was established. Delirium symptoms were measured with the Confusion Assessment Method on days 1, 3, 5, 8, 15 and 21. Covariates studied were comorbidities ( Charlson), health status, activities of daily living, nutrition (albumin), cognition, length of stay and mortality. Results A total of 51.6% of the patients were taking anticholinergic drugs at home (2.13 ± 1.34). Length of stay was 14.5 ± 9.9 days. Prevalence of delirium symptoms ranged on days between 34.8 and 60%. Anticholinergic burden was correlated with the appearance of delirium symptoms. Delirium symptoms were associated with greater mortality (16.1 and 3.7 % in patients with and without delirium symptoms; P = 0.049), a longer hospital stay (18.09 ± 11.34 vs 11.75 ± 7.80 days, P = 0.001), greater dependence on discharge (activities of daily living score: 1.57 ± 1.56 vs 3.41 ± 1.45, P < 0.0001) and worse health status on discharge (5.3 ± 2.7 vs 7.0 ± 1.7, P = 0.0008). Conclusion Anticholinergic burden appears as a risk factor for both delirium symptoms and mortality. Prevention of delirium symptoms requires its reduction Geriatr Gerontol Int 2016; 16: 424-431. [ABSTRACT FROM AUTHOR]

Objectives To describe the characteristics of nursing home residents diagnosed with atrial fibrillation ( AF) and eligible for oral anticoagulants who did not receive these drugs and to detail the conditions that physicians who decide not to prescribe anticoagulants take into account. Design Cross-sectional. Setting Nursing home. Participants Nursing home residents with a history of AF (N = 1,085). Measurements Data were collected on clinical characteristics, geriatric syndromes, and antithrombotic regimen. Multivariate logistic regression was used to identify factors associated with nonprescription of anticoagulants. A standardized questionnaire was submitted to physicians in charge of patients with AF, to detail conditions associated with their medical decision not to prescribe anticoagulants. Results History of AF was present in 1,085 nursing home residents (10.1%), mean age 87, with a mean CHA2 DS2- VASc score of 5.1 ± 1.4. Of these residents with AF, 544 (50.1%) did not receive anticoagulants. Recurrent falls (odds ratio ( OR) = 4.9, 95% confidence interval ( CI) = 2.4-9.9, P < .001), past history of bleeding ( OR = 3.62, 95% CI = 1.54-8.51, P = .003), paroxysmal AF ( OR = 3.5, 95% CI = 1.83-6.66, P < .001), and advanced age ( OR = 1.1, 95% CI = 1.01-1.17, P = .02) were significantly associated with not prescribing anticoagulants. Recurrent falls (47%), cognitive impairment (22.6%), and advanced age (16.4%) were the main reasons for not prescribing anticoagulants. Conclusion The prevalence of AF in a cohort of very old nursing home residents was 10%. Anticoagulation was prescribed in fewer than 50% of eligible cases despite high individual risk of stroke. Geriatric syndromes, especially falls and cognitive disorders, were the main reported contraindications for prescribing anticoagulants. Physicians caring for those residents wrongly thought that paroxysmal AF caused fewer thromboembolic events than permanent AF, which explains lower rates of anticoagulant prescription in individuals with paroxysmal AF. [ABSTRACT FROM AUTHOR]

The article presents information on a study to compare the relationships between ventricular morphology, cerebrospinal fluid (CSF) flow, and white matter diffusion in Alzheimer's disease (AD) and normal-pressure hydrocephalus (NPH). The study was conducted on thirty patients that underwent a 3-Tesla magnetic resonance imaging (MRI) scan. It is concluded that although both AD and NPH involve CSF disorders, they do not have similar impact on internal capsules.

Background: The appearance of Aβ42 peptide deposits is admitted to be a key event in the pathogenesis of Alzheimer's disease, although amyloid deposits also occur in aged non-demented subjects. Aβ42 is a degradation product of the amyloid protein precursor (APP). It can be catabolized by several enzymes, reabsorbed by capillaries or cleared into cerebrospinal fluid (CSF). The possible involvement of a decrease in CSF turnover in A4β2 deposit formation is up to now poorly known. We therefore investigated a possible relationship between a reduced CSF turnover and the CSF levels of the A4β2 peptide. To this aim, CSF of 31 patients with decreased CSF turnover were studied. These patients presented chronic hydrocephalus communicating or obstructive, which required surgery (ventriculostomy or ventriculo-peritoneal shunt). Nine subjects had idiopathic normal pressure hydrocephalus (iNPH), and the other 22 chronic hydrocephalus from other origins (oCH). The Aβ42 peptide concentration was measured by an ELISA test in 31 ventricular CSF samples and in 5 lumbar CSF samples from patients with communicating hydrocephalus. Results: The 5 patients with lumbar CSF analysis had similar levels of lumbar and ventricular Aβ42. A significant reduction in Aβ42 ventricular levels was observed in 24 / 31 patients with hydrocephalus. The values were lower than 300 pg/ml in 5 out of 9 subjects with iNPH, and in 15 out of 22 subjects with oCH. Conclusion: The decrease of CSF Aβ42 seems to occur independently of the surgical hydrocephalus aetiology. This suggests that a CSF reduced turnover may play an important role in the decrease of CSF Aβ42 concentration. [ABSTRACT FROM AUTHOR]

Background: Comprehensive geriatric assessments of patients entering the severe stage of Alzheimer’s disease (AD) are scarce. Methods: Cross-sectional study of 126 patients entering the severe stage of AD in the longitudinal study of REAL.FR cohort. Patients who had a first MMSE score <10 during follow-up underwent cognitive, behavioral, nutritional and functional assessment. Support requirements were also evaluated. Results: The best-preserved cognitive abilities were social interaction and response to own name, while praxis, orientation, memory and language showed the largest declines. Regarding independence in daily living, locomotion was best preserved (71% of patients independent) while personal hygiene deteriorated most (15.5%). Behavioral disorders were frequent, and consisted principally of apathy, aberrant motor behavior, and agitation. The Mini Nutritional Assessment showed that 68.5% of patients were malnourished or at risk of malnutrition. Caregiver burden remained mild to moderate in 69.8% of cases. In addition, 80% of patients still lived at home and 71.6% used at least 2 support services, consisting mainly of physician visits and home help. Conclusion: Assessment of remaining cognitive, functional abilities and behavioral disorders at entry to severe AD should help to improve targeted management aimed at preserving these abilities and treating complications, thereby optimizing these patients’ quality of life. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: The appearance of Aβ42 peptide deposits is admitted to be a key event in the pathogenesis of Alzheimer's disease, although amyloid deposits also occur in aged non-demented subjects. Aβ42 is a degradation product of the amyloid protein precursor (APP). It can be catabolized by several enzymes, reabsorbed by capillaries or cleared into cerebrospinal fluid (CSF). The possible involvement of a decrease in CSF turnover in A4β2 deposit formation is up to now poorly known. We therefore investigated a possible relationship between a reduced CSF turnover and the CSF levels of the A4β2 peptide.To this aim, CSF of 31 patients with decreased CSF turnover were studied. These patients presented chronic hydrocephalus communicating or obstructive, which required surgery (ventriculostomy or ventriculo-peritoneal shunt). Nine subjects had idiopathic normal pressure hydrocephalus (iNPH), and the other 22 chronic hydrocephalus from other origins (oCH).The Aβ42 peptide concentration was measured by an ELISA test in 31 ventricular CSF samples and in 5 lumbar CSF samples from patients with communicating hydrocephalus.Results: The 5 patients with lumbar CSF analysis had similar levels of lumbar and ventricular Aβ42. A significant reduction in Aβ42 ventricular levels was observed in 24 / 31 patients with hydrocephalus. The values were lower than 300 pg/ml in 5 out of 9 subjects with iNPH, and in 15 out of 22 subjects with oCH.Conclusion: The decrease of CSF Aβ42 seems to occur independently of the surgical hydrocephalus aetiology. This suggests that a CSF reduced turnover may play an important role in the decrease of CSF Aβ42 concentration. [ABSTRACT FROM AUTHOR]