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Objective Several studies have reported poor long-term neuropsychological performances in patients following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, but none has yet considered the effect of administering multiple intercorrelated neuropsychological tests and assessed the frequency of cognitive deficits in a normative population. Our aim was therefore to assess the presence of cumulative neuropsychological deficits in an actual post-coronavirus disease of 2019 (COVID-19) comparison group versus one simulated using Monte-Carlo methods. Method Validated neuropsychological Monte-Carlo simulation methods were applied to scores from a battery of neuropsychological tests (memory, executive, attentional, perceptual, logical reasoning, language, and ideomotor praxis) administered to 121 patients who had had mild, moderate, or severe COVID-19 (mean age: 56.70 years; 32% women), 222 ± 43 days post-infection. The cumulative percentages of the three severity subgroups were compared with the results of a false discovery rate-corrected probability analysis based on normative data. Results The cumulative percentages of deficits in memory and executive functions among the severe and moderate patients were significantly higher than those estimated for the normative population. Moderate patients also had significantly more deficits in perception and logical reasoning. In contrast, the mild group did not have significantly more cumulative deficits. Conclusions Moderate and severe forms of COVID-19 cause greater long-term neuropsychological deficits than those that would be found in a normative population, reinforcing the hypothesis of long-term effects of SARS-CoV-2 on cognitive function, independent of the severity of the initial infection.

Background Age alone is not a robust predictor of mortality in critically ill elderly patients. Chronic health status and functional status before admission could be better predictors. This study aimed to determine whether functional status, assessed using the Functional Independence Measure (FIM), could be an independent predictor of mortality in a geriatric population admitted to an intermediate care unit (IMCU). Methods A monocentric, retrospective, observational study of all patients aged ≥75 years old admitted to Geneva University Hospitals’ geriatric IMCU between 01.01.2012 and 31.05.2016. The study’s primary outcome metrics were one-year mortality’s associations with a pre-admission FIM score and other relevant prospectively recorded prognostic variables. Results A total of 345 patients were included (56% female, mean age 85 +/− 6.5 years). Mean FIM score was 66 +/− 26. One-year mortality was 57%. Dichotomized low (≤ 63) and high FIM (> 63) scores were associated with one-year mortalities of 68 and 44%, respectively. Logistic regression calculations found an association between pre-admission FIM score and one-year mortality (p Conclusions In the present study, higher functional status, assessed using the FIM tool before admission to an IMCU, was significantly and independently associated with lower one-year mortality. This opens up perspectives on the potential value of FIM for establishing a finer prognosis and better triage of critically ill older patients.

Additional file 1. Appendix. Screened cohort’s baseline characteristics at IMCU admission according to FIM availability. Figure 1 with normal distribution of the mains continuous/categorical variable.

Item does not contain fulltext Patient groups prone to polypharmacy and special subpopulations are susceptible to suboptimal treatment. Refined dosing in special populations is imperative to improve therapeutic response and/or lowering the risk of toxicity. Model-informed precision dosing (MIPD) may improve treatment outcomes by achieving the optimal dose for an individual patient. There is, however, relatively little published evidence of large-scale utility and impact of MIPD, where it is often implemented as local collaborative efforts between academia and healthcare. This article highlights some successful applications of bringing MIPD to clinical care and proposes strategies for wider integration in healthcare. Considerations are brought up herein that will need addressing to see MIPD become "widespread clinical practice," among those, wider interdisciplinary collaborations and the necessity for further evidence-based efficacy and cost-benefit analysis of MIPD in healthcare. The implications of MIPD on regulatory policies and pharmaceutical development are also discussed as part of the roadmap.

Lipid-lowering treatment in the elderly patient is conditioned by a high incidence and prevalence of cardiovascular disease in the setting of a limited remaining life span. The clinical benefit of statin therapy can be seen after a few months, thus supporting use in secondary prevention even when the lifespan is restricted to a few years. Recent guidelines propose the use of moderate doses in the elderly75 years. The evidence for treatment in primary prevention is weaker and the evaluation of the total cardiovascular risk is complicated by the high baseline risk of many elderly. Rational treatment decisions should be based on biologic rather than chronologic age. Statins are generally well tolerated in the elderly, requiring clinical monitoring only, with particular attention to pharmacokinetic interactions and renal failure.

Clostridium difficile infection (CDI) epidemiology has changed with an increase in incidence and severity, particularly among the elderly.

Purpose. – The observation of inherited drug response variability gave rise to the field of pharmacogenetics. Pharmacogenetic research on drug targets, particularly platelet enzymes and receptors, is more recent and is becoming an emerging field. Current knowledge and key points. – In the Framingham study, the heritability of platelet aggregation response ranges from 44 to 62%, depending on the agonists used. The gene coding for GPIIIa, a sub-unit of the fibrinogen receptor GPIIbIIIa, is one of the most extensively studied gene in relation with aggregation tests and antiplatelet drugs. The GPIIIa PLA1/PLA2 polymorphism has been associated with clopidogrel and orbofiban platelet response. However, data are more controversial concerning the association with aspirin response. Recently, Cox-1 and GPIa (part of the GPIaIIa collagen receptor) genetic variations have also been pointed out as possible candidates to explain part of the variability of the response to antiplatelet agents. Finally, the H1/H2 polymorphism of the platelet ADP receptor P2Y12 gene has been associated with ADP-induced platelet aggregation response and peripheral arterial disease. This polymorphism may modulate the effect of P2Y12 antagonists like clopidogrel and its clinical implication is currently under study. Future prospects and projects. – Gene-expression profiling and proteomics may allow the identification of new candidate genes whose variations may be associated with the heritability of platelet aggregation response. In the next future, phenotypic or genotypic studies could be available to tailor the prescription of antiplatelet drugs.

When enteral nutrition is indicated to prevent or to treat a patient with denutrition choosing between a nasogastric tube (NGT) and a percutaneous endoscopic gastrostomy (PEG) is not always an easy decision. In neurological patients with swallowing disturbances or in patients with head and neck tumors, PEG is associated with lower rates of feeding tube dislodgement, while NGT has lower rates or morbidity. A meta-analysis showed that the interruption of nutrition is less frequent with PEG but there is no difference in terms of mortality and aspiration pneumonia between PEG and NGT. The European Society for Clinical Nutrition and Metabolism recommends PEG when enteral nutrition is expected to last more than 3 weeks.

To assess the practical implementation of international guidelines and their impact on syncope management in a 500-bed general hospital.Three groups of 63 consecutive patients admitted for syncope to the emergency care unit (ECU) were studied: group 1, before the guidelines delivered to the practitioners, group 2 immediately after the diffusion of guidelines and group 3, one year later. The study evaluates the mean duration of stay (MDS) and the relevance of the diagnostic strategy.In group 1 compared to group 2, MDS were respectively 6.8±5.5 and 5.4±2.8 days (P=0.07) and the unexplained syncope number respectively 22% and 24% (P=0.8). The search of orthostatic hypotension became more systematic (13% versus 86% in group 1 and 2 respectively, P0.001). The agreement (kappa coefficient) between initial and final diagnostic increased in 0.34 to 0.44. One year later MDS in group 3 was 7.1±4.7 days (P=0.8 versus group 1 and P=0.015 versus group 2) with only 6.3% systematic search for orthostatic hypotension (P0.001).Guidelines optimize the syncope management in the ECU and the agreement between the emergency and discharge diagnostic without change of unexplained syncope and. MDS tend to be shorter when guidelines are actively implemented. Nevertheless, the positive impact of guidelines implementation is of limited duration.

A poor biological response to clopidogrel is associated with an increased risk of major cardiovascular ischemic events (MACE). Paraoxonase 1 (PON1) enzyme activity is modulated by the PON1-Q192R variant (rs662) and was recently suggested to be strongly involved in clopidogrel bioactivation, but the influence of the PON1-Q192R variant on the risk of MACE in clopidogrel-treated patients is controversial.To determine whether the PON1-Q192R variant influences clopidogrel biological responsiveness and the risk of MACE in patients treated with clopidogrel.Systematic review and meta-analysis of studies of the association between the PON1-Q192R polymorphism and the biological response to clopidogrel and/or the risk of MACE during clopidogrel administration.Seventeen studies were included. In the 12 studies of the biological response to clopidogrel (n = 5302 patients), there was no significant difference between 192QQ and 192QR + 192RR subjects, whatever the laboratory method used (global mean standardized difference = 0.10 [-0.06; 0.25], P = 0.22). Eleven studies assessed the risk of MACE, four using a case-control design (n = 2739 patients) and seven a prospective design (n = 5353 patients). Overall, MACE occurred in 19% of patients in case-control studies and in 6% of patients in prospective cohort studies, with no significant difference between 192QQ and 192QR + 192RR patients (OR = 1.28 [0.97; 1.68], P = 0.08). Similar results were obtained when study design was taken into account. Heterogeneity was mainly driven by one publication.This meta-analysis suggests that the PON1-Q192R polymorphism has no major impact on the risk of MACE and does not alter the biological response to clopidogrel in clopidogrel-treated patients.

A 53-year-old man is treated by L-asparaginase for an acute lymphoblastic leukaemia. He received anti thrombin infusions. A systematic electrocardiogram showed an asymptomatic subepicardium ischemia without troponin elevation. Echocardiography and heart magnetic resonance imaging showed an apical thrombus facing a zone of myocardial necrosis. A thrombus regression was observed under anticoagulation. Atypical and asymptomatic coronary thrombosis may occur following L-asparaginase treatment. Regular electrocardiogram monitoring is proposed along this treatment. Arterial thrombosis associated with anti tumor chemotherapies are reviewed.

BSUMMARY BACKGROUND: Previous studies have shown an important risk of cardiovascular events in patients with clopidogrel biological non-response, and data have shown considerable, unexplored heterogeneity. OBJECTIVES: To evaluate the magnitude of cardiovascular risk associated with clopidogrel non-response and to explore heterogeneity. METHODS: This was a systematic review and meta-analysis of prospective studies of patients treated with clopidogrel for symptomatic atherothrombosis, evaluated by light transmission aggregometry with ADP and monitored prospectively for clinical ischemic events. RESULTS: Fifteen studies were included, totaling 3960 patients, of whom 25% were considered to be clopidogrel non-responders. The global relative risk (RR) for recurrent ischemic events in clopidogrel non-responders was 3.5 [95% confidence interval (CI) 2.4-5.2, P < 0.0001]. The results of the different studies were heterogeneous (Cochran P = 0.01 and I(2) = 52%). The most recent studies yielded lower RRs [global RR = 2.9 (95% CI 2.3-3.8) after 2007, and global RR = 6.6 (95% CI 3.7-11.9) before 2007, P = 0.01]. Heterogeneity was present in the group of studies in which more than 10% of patients took glycoprotein (GP)IIb-IIIa inhibitors [Cochran P = 0.003 and I(2) = 70%; RR = 3.8 (95% CI 2.9-5.1)] and was absent in the other studies [Cochran P = 0.88 and I(2) = 0; RR = 2.5 (95% CI 1.7-3.6)]. The RR was significantly higher in studies using higher ADP maximal aggregation cut-offs (> 65%) for clopidogrel non-response than in studies using lower cut-offs [RR = 5.8 (95% CI 3.2-10.3) and RR = 2.9 (95% CI 2.2-3.7), respectively, P = 0.03]. CONCLUSIONS: The risk of ischemic events associated with clopidogrel non-response is now more precisely defined. The risk is heterogeneous across studies, possibly because of an interaction with GPIIb-IIIa inhibitors and the use of different cut-offs to identify non-responders.

Aspirin, a 110-year-old molecule, is a cornerstone in the treatment of atherothrombotic patients. The concept of aspirin "resistance" emerged approximately 15 years ago and is of growing interest. Aspirin resistance, defined as a lack of inhibition of cyclo-oxygenase-1 (COX-1), is a rare phenomenon and its clinical relevance can hardly be studied. On the contrary, residual platelet hyperactivity is more common and affects 20 to 30% of aspirin-treated patients. This latter phenomenon corresponds to sustained platelet reactivity despite a proper inhibition of COX-1 by aspirin. Several meta-analyses suggest that residual platelet hyperactivity could be a risk factor for the recurrence of ischemic events in aspirin-treated patients. Causes of biological non-responsiveness to aspirin are discussed, including the role of compliance, drug-drug interactions, genetic polymorphisms and diabetes mellitus. Ongoing studies are designed to find out the mechanisms of residual platelet hyperactivity, determine its potential clinical relevance and delineate the more appropriate assays in order to identify patients who may benefit of a tailored antiplatelet therapy.

Antiphospholipid antibodies (aPL) can be associated with numerous infectious and particularly Q fever. Data on the pathogenicity of aPL in the course of acute Q fever are scarce.We report the case an acute Coxiella burnetii infection associated with clinical and biological manifestations of the aPL syndrome, including a renal infarction. Along with antibiotic treatment, anticoagulation and intravenous immunoglobulins, the clinical outcome was favourable. Antiphospholipid antibodies and Q fever antibody titers had a closely related evolution.Arterial thrombosis associated with Q fever and aPL is exceptional. The nosology and potential mechanisms are discussed.

Antiplatelet agents (APA), statins and angiotensin converting enzyme inhibitors (ACEI) are effective to reduce the risk of cardio-vascular events in patients with peripheral arterial disease (PAD). Few data are available on the actual prescription of these drugs in outpatients and on the effect of hospital care on the level of prescription.Retrospective study of patients hospitalized with a confirmed diagnosis of PAD over a one-year period. Comparison of medical treatments on admission and on discharge.262 patients were included. Mean age was 73 +/- 11 years, and 29% of the patients were women. APA were present in 64% on admission and in 83% when discharged (P0.0001). A statin was present in 29% on admission and in 38% when discharged (P = 0.001). ACEI were present in 27% on admission and in 32% when discharged (P= 0.02). A vasodilator was present in 47% on admission and 52% when discharged (P = 0.1). 35% of the patients had isolated PAD. Compared to the patients with associated clinical coronary or cerebro-vascular disease, they were less frequently discharged on statins (respectively 26 and 45%, p = 0.003) and on ACEI (respectively 23 et 38%, P = 0.016) whereas APA were equally prescribed (respectively 82 and 84%, P= 0.7).APA were prescribed to a majority of outpatients and the level of prescription was further improved when patients were discharged from the hospital. Statins and ACEI were insufficiently prescribed. On the other hand, vasodilator therapy remained still largely prescribed, despite the lack of any strong effect on morbidity and survival.

Articles on antiplatelet "resistance" or "nonresponder" subjects now appear in the medical literature or in the media on a regular basis. The clinical consequences of such biological resistances are yet uncertain. In this review, we describe the concepts of specific and non specific resistances according to the tests used and summarize the main studies up to now. If antiplatelet drug resistances are shown to be predictive of cardiovascular events in large prospective studies, tailoring antiplatelet drugs could be beneficial and, therefore, warranted. New compounds with a more potent effect are emerging and might be useful in clinically relevant resistances.

The observation of inherited drug response variability gave rise to the field of pharmacogenetics. Pharmacogenetic research on drug targets, particularly platelet enzymes and receptors, is more recent and is becoming an emerging field.In the Framingham study, the heritability of platelet aggregation response ranges from 44 to 62%, depending on the agonists used. The gene coding for GPIIIa, a sub-unit of the fibrinogen receptor GPIIbIIIa, is one of the most extensively studied gene in relation with aggregation tests and antiplatelet drugs. The GPIIIa PLA1/PLA2 polymorphism has been associated with clopidogrel and orbofiban platelet response. However, data are more controversial concerning the association with aspirin response. Recently, Cox-1 and GPIa (part of the GPIaIIa collagen receptor) genetic variations have also been pointed out as possible candidates to explain part of the variability of the response to antiplatelet agents. Finally, the H1/H2 polymorphism of the platelet ADP receptor P2Y12 gene has been associated with ADP-induced platelet aggregation response and peripheral arterial disease. This polymorphism may modulate the effect of P2Y12 antagonists like clopidogrel and its clinical implication is currently under study.Gene-expression profiling and proteomics may allow the identification of new candidate genes whose variations may be associated with the heritability of platelet aggregation response. In the next future, phenotypic or genotypic studies could be available to tailor the prescription of antiplatelet drugs.

Infection is a common problem in diabetic patients with foot ulcers. The diagnosis of infection is not always easy to establish, but must be made for proper therapeutic decision making. In addition to local care, search for arteriopathy and strict control of blood glucose, treatment of infected foot ulcers requires an appropriate anti-infectious strategy. We developed diagnostic and therapeutic decisional algorithms from data available in the literature in order to establish a management strategy for different clinical situations. The fundamental role of clinical assessment is underlined and the different causal microorganisms are recalled, together with the anti-microbial activity and bone concentrations of the main antibiotics used. An optimal anti-infection work-up can undoubtedly significantly reduce the number of amputations in diabetic patients.

In the past, the diagnosis and course of Takayasu arteritis were monitored by following angiographic findings, in addition to clinical symptoms and biological tests. More recently, cross-sectional imaging techniques especially Computed Tomography (CT) depicted mural changes in aorta and main vessels in this disease. Within the same acquisition, spiral mode also allows to show luminal changes, similarly to conventional angiography. In addition to its diagnostic value especially in the early phase of the disease, CT seems accurate in the follow-up of treated patients and may be proposed as a therapeutic guide. CT features are presented, according to the stage of the disease and the vessels involved.

To review clinical data, pathophysiology and treatment of thromboangiitis (Buerger's disease).Buerger's disease or thromboangiitis obliterans (TAO) is an obliterative vascular disease that affects medium and small sized arteries as well as superficial veins. Young males and smokers are preferentially afflicted with the disease. TAO accounts for 0.5 to 5% of occlusive vascular disease. Though TAO has a world-wide distribution, it can be found with greater prevalence in Eastern Europe, the Mid-East, Asia, and Southeast Asia. Women account for 10 to 20% of the patients and 5 to 10% are more than 60-years-old. Approximately 95% are smokers and disease activity is strongly associated with the use of tobacco. The pathogenesis is poorly understood and most hypotheses are controversial. There is no specific marker of the disease and the diagnosis is based on clinical and angiographic criteria. The disease spontaneously leads to tissue loss and major amputations. This can generally be avoided by discontinuing smoking. Induced hypervolemia and prostacyclins are effective treatments of critical limb ischemia in TAO.If pathophysiology is still poorly understood, spontaneous evolution can be avoided by stopping tobacco and prostacyclin.

In 2012, several countries have reported increased Norovirus (NoV) activity attributable to the emergence of a new variant (strain GII.4 Sydney). We describe an outbreak caused by this strain in a geriatric hospital.