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Background Elective surgeries can be associated with significant harm to older adults. The present study aimed to identify the prognostic factors associated with the development of postoperative complications among older adults undergoing elective surgery. Methods Medline, EMBASE, CINAHL, Cochrane Central Register of Controlled Trials, and AgeLine were searched for articles published between inception and April 21, 2016. Prospective studies reporting prognostic factors associated with postoperative complications (composite outcome of medical and surgical complications), functional decline, mortality, post-hospitalization discharge destination, and prolonged hospitalization among older adults undergoing elective surgery were included. Study characteristics and prognostic factors associated with the outcomes of interest were extracted independently by two reviewers. Random effects meta-analysis models were used to derive pooled effect estimates for prognostic factors and incidences of adverse outcomes. Results Of the 5692 titles and abstracts that were screened for inclusion, 44 studies (12,281 patients) reported on the following adverse postoperative outcomes: postoperative complications ( n =28), postoperative mortality ( n  = 11), length of hospitalization ( n  = 21), functional decline ( n  = 6), and destination at discharge from hospital ( n  = 13). The pooled incidence of postoperative complications was 25.17% (95% confidence interval (CI) 18.03–33.98%, number needed to follow = 4). The geriatric syndromes of frailty (odds ratio (OR) 2.16, 95% CI 1.29–3.62) and cognitive impairment (OR 2.01, 95% CI 1.44–2.81) were associated with developing postoperative complications; however, there was no association with traditionally assessed prognostic factors such as age (OR 1.07, 95% CI 1.00–1.14) or American Society of Anesthesiologists status (OR 2.62, 95% CI 0.78–8.79). Besides frailty, other potentially modifiable prognostic factors, including depressive symptoms (OR 1.77, 95% CI 1.22–2.56) and smoking (OR 2.43, 95% CI 1.32–4.46), were also associated with developing postoperative complications. Conclusion Geriatric syndromes are important prognostic factors for postoperative complications. We identified potentially modifiable prognostic factors (e.g., frailty, depressive symptoms, and smoking) associated with developing postoperative complications that can be targeted preoperatively to optimize care.

This study aimed to assess patient investigational medication knowledge and to identify factors associated with medication understanding by adult outpatients included in clinical trials. A cross-sectional prospectively designed survey was conducted on consecutive volunteers at 21 university teaching hospitals (in France) from February to December 2014. Investigational medication understanding was assessed at the time of the first dispensing using a structured interviewer-administered questionnaire based on information obtained from the literature that provided an 8-point score. Demographic and other baseline data were collected using structured interviews. Of the 236 participants, 139 (58.9%) of the respondents were male, and the median age was 54.9 years (range: 18-83 years). The mean understanding score was 6.24 and 72.5% of the patients had a score of 6 or higher. In univariate analysis, the medication understanding score was negatively correlated with age (r = -0.15, p = 0.0247) and positively correlated with the level of education (r = 0.25, p = 0.0002). In multivariate analysis, prognostic factors of a higher medication understanding score were: graduation from high school or a higher level of education; HIV infection; phase II/III/IV studies; mention of the drug on the prescription form, and the dispensing of a single investigational medication. Only a quarter of the adult outpatients included in clinical trials had a maximum possible investigational medication understanding score. Being old and having a low level of education were found to be important risk factors for inadequate medication understanding. This and other data suggest that sponsors should encourage initiatives aimed at improving investigational medication understanding in adults enrolled in clinical trials.

The purpose of this paper is to present an edge pervasive platform supporting the development, deployment and management of flexible, context-aware pervasive applications. This platform, named iCasa, is built on top of the OSGi/iPOJO service-oriented component model. It includes an autonomic context module connected to the physical environment and providing information as a dynamic set of services. This context is dynamic in order to reflect the changing nature of the execution environment but also to deal with applications evolving needs. ICasa also comes with an Eclipse-base development environment including a source code editor, build automation tools, automated deployment facilities, and a smart home configurator and simulator. ICasa has been validated on a variety of applications, mostly in collaboration with Orange Telecom company and Schneider Electric. It is available on the Internet (self-star.net) and is heavily used today for teaching purposes, in addition to industrial developments.

BackgroundPostoperative delirium is a common preventable complication experienced by older adults undergoing elective surgery. In this systematic review and meta-analysis, we identified prognostic factors associated with the risk of postoperative delirium among older adults undergoing elective surgery.MethodsMedline, EMBASE, CINAHL, Cochrane Central Register of Controlled Trials, and AgeLine were searched for articles published between inception and April 21, 2016. A total of 5692 titles and abstracts were screened in duplicate for possible inclusion. Studies using any method for diagnosing delirium were eligible. Two reviewers independently completed all data extraction and quality assessments using the Cochrane Risk-of-Bias Tool for randomized controlled trials (RCTs) and the Newcastle-Ottawa Scale (NOS) for cohort studies. Random effects meta-analysis models were used to derive pooled effect estimates.ResultsForty-one studies (9384 patients) reported delirium-related prognostic factors. Among our included studies, the pooled incidence of postoperative delirium was 18.4% (95% confidence interval [CI] 14.3–23.3%, number needed to follow [NNF] = 6). Geriatric syndromes were important predictors of delirium, namely history of delirium (odds ratio [OR] 6.4, 95% CI 2.2–17.9), frailty (OR 4.1, 95% CI 1.4–11.7), cognitive impairment (OR 2.7, 95% CI 1.9–3.8), impairment in activities of daily living (ADLs; OR 2.1, 95% CI 1.6–2.6), and impairment in instrumental activities of daily living (IADLs; OR 1.9, 95% CI 1.3–2.8). Potentially modifiable prognostic factors such as psychotropic medication use (OR 2.3, 95% CI 1.4–3.6) and smoking status (OR 1.8 95% CI 1.3–2.4) were also identified. Caregiver support was associated with lower odds of postoperative delirium (OR 0.69, 95% CI 0.52–0.91).DiscussionThough caution must be used in interpreting meta-analyses of non-randomized studies due to the potential influence of unmeasured confounding, we identified potentially modifiable prognostic factors including frailty and psychotropic medication use that should be targeted to optimize care.

Background Older adults are more vulnerable to severe infection and mortality due to COVID-19. They have atypical presentations of the disease without respiratory symptoms, making early diagnosis clinically challenging. We aimed to compare the baseline characteristics, presentation, and disease course of older (≥70 yrs & ≥90 yrs) and younger (<70 yrs) patients hospitalized with COVID-19. Methods Retrospective review of 429 consecutive patients hospitalized at two tertiary care hospitals in Montreal, Canada, with PCR-confirmed COVID-19. Baseline characteristics, presentation, in-hospital complications, and outcomes were recorded. Desegregation by age was performed to compare older versus younger individuals. Additional subgroup analyses were performed amongst patients ≥70 stratifying by sex, living situation, and those presenting with geriatric syndromes compared to those without. Results Patients ≥70 (n=260) presented less frequently with respiratory symptoms compared to patients <70 (n=169) (52% vs. 32%). 11% of patients ≥70 and 24% of patients ≥90 presented with a geriatric syndrome as their sole symptom compared to 3% of those <70. Older adults were more likely to develop disease complications (including delirium, acute kidney injury, and hypernatremia) and had higher in-hospital mortality (32% vs. 13%). Subgroup analyses revealed heightened vulnerability to complications in older men, those from long-term care, and those with at least one geriatric syndrome upon presentation. Conclusions Older adults presenting to hospital with COVID-19 often have no respiratory symptoms and can present with only a geriatric syndrome. New geriatric syndromes in older individuals should trigger evaluation for COVID-19 and consideration for early initiation of multidisciplinary care to prevent complications.

BACKGROUND: Frailty, a state of decreased physiological reserve predisposing to adverse health events, including delirium, is prevalent in older patients undergoing cardiac procedures. In turn, delirium, an acute confusional state, predisposes to frailty in a vicious cycle. So far, most promising measures to prevent delirium, and potentially frailty, in medical and surgical patients, are non-pharmacological in nature. In the context of cardiac surgery, such interventions have infrequently been studied and no standard of care has been established.AIMS: Using a Delphi Consensus Survey, we sought to determine which components should be included in a non-pharmacologic intervention bundle aiming at delirium prevention and treatment in patients undergoing cardiac surgery.METHODS: Twenty multidisciplinary experts with knowledge and experience in delirium management in patients undergoing cardiac surgical procedures were approached to provide five suggestions of components to include in a non-pharmacologic delirium prevention and treatment intervention specific to this population. These suggestions were analyzed in duplicate by two independent investigators who grouped them into categories of components. A second iteration was then distributed to the same experts, asking them to rate each category of components on a 7-point Likert scale with regards to its importance, feasibility, and risk for adverse events.RESULTS: Thirteen and eleven out of the twenty experts respectively answered the two iterations of our survey. Ten categories of components were generated from the participants' propositions. Aside from components known to be effective in other clinical settings, our panel identified pain and anxiety management, family and healthcare workers education as well as delirium screening and treatment planning to be of specific interest to cardiac surgical patients. After two rounds of the Delphi Survey, consensus was reached on the high importance and the low risk of adverse events of most categories. No consensus was achieved with regards to the feasibility of the different categories of components, as it was felt by many respondents to rely excessively on individual institutions' cultures and practices.CONCLUSION: Our work allowed us to identify ten categories of components to potentially include in a multicomponent non-pharmacologic delirium prevention and treatment intervention specific to cardiac surgical patients.

Hepcidin regulates plasma iron bioavailability and subsequently iron availability for erythropoiesis. rHuEPO has been reported to decrease hepcidin expression in case of repeated subcutaneous injections. Thus, hepcidin level measurement could be a candidate marker for detection of rHuEPO abuse. However, when used for doping, rHuEPO can be injected intravenously and the scheme of injection is unknown. Our aim was to evaluate the early effects of a single intravenous rHuEPO injection on serum hepcidin levels. Fourteen male healthy volunteers received one intravenous injection of 50 U/Kg of rHuEPO during a placebo-controlled, randomized, double-blind, cross-over study. Serum hepcidin, quantified by a competitive ELISA method and iron parameters was then evaluated for 24 h. Serum levels of hepcidin were significantly increased 4 h after rHuEPO injection when compared with placebo injection (78.3 ± 55.5 vs. 57.5 ± 34.6 ng/ml, respectively; +36%, p  < 0.05), whereas iron and transferrin saturation dramatically decreased 12 h after rHuEPO injection when compared with placebo injection (9.2 ± 3.5 vs. 15.8 ± 4.2 μg/l, respectively; −42%, p  < 0.05 and 14.8 ± 5.0 vs. 26.3 ± 6.4%, respectively; −44%, p  < 0.05). In addition, 12 and 24 h after rHuEPO injection serum hepcidin levels were lower compared with placebo injection (41.6 ± 27.4 vs. 56.6 ± 28.1 ng/ml after 12 h; −27%, p  < 0.05 and 26.0 ± 29.6 vs. 81.2 ± 29.4 ng/ml after 24 h; −68%, p  < 0.05). Intravenous injection of recombinant EPO induces a precocious and transient increase of serum hepcidin leading to a transient decrease of iron bioavailability. The transitory increase and dynamics of its concentration make difficult the practical use of hepcidin to detect rHuEPO doping.

Macrophages have a key role in shaping the tumour microenvironment (TME), tumour immunity and response to immunotherapy, which makes them an important target for cancer treatment 1 , 2 . However, modulating macrophages has proved extremely difficult, as we still lack a complete understanding of the molecular and functional diversity of the tumour macrophage compartment. Macrophages arise from two distinct lineages. Tissue-resident macrophages self-renew locally, independent of adult haematopoiesis 3 – 5 , whereas short-lived monocyte-derived macrophages arise from adult haematopoietic stem cells, and accumulate mostly in inflamed lesions 1 . How these macrophage lineages contribute to the TME and cancer progression remains unclear. To explore the diversity of the macrophage compartment in human non-small cell lung carcinoma (NSCLC) lesions, here we performed single-cell RNA sequencing of tumour-associated leukocytes. We identified distinct populations of macrophages that were enriched in human and mouse lung tumours. Using lineage tracing, we discovered that these macrophage populations differ in origin and have a distinct temporal and spatial distribution in the TME. Tissue-resident macrophages accumulate close to tumour cells early during tumour formation to promote epithelial–mesenchymal transition and invasiveness in tumour cells, and they also induce a potent regulatory T cell response that protects tumour cells from adaptive immunity. Depletion of tissue-resident macrophages reduced the numbers and altered the phenotype of regulatory T cells, promoted the accumulation of CD8 + T cells and reduced tumour invasiveness and growth. During tumour growth, tissue-resident macrophages became redistributed at the periphery of the TME, which becomes dominated by monocyte-derived macrophages in both mouse and human NSCLC. This study identifies the contribution of tissue-resident macrophages to early lung cancer and establishes them as a target for the prevention and treatment of early lung cancer lesions. Single-cell RNA sequencing and imaging of macrophages in human non-small cell lung cancer and in a mouse model of lung adenocarcinoma show that tissue-resident macrophages have a key role in early tumour progression.

High-frequency and multi-elemental stream water monitoring are acknowledged as necessary to address data limitation in the fields of catchment sciences and freshwater biogeochemistry. In recent years, the development of stream bank analyzers and on-site field laboratories to measure various solutes and/or isotopes at sub-hourly measurement intervals has been in progress at an increasing number of sites. This trend should likely persist in the future as the technologies are still improving. Here we share our experiences of running three innovative lab-in-the-field prototypes, called Riverlabs, which consist of a field deployment involving continuous sampling and filtration of stream water and its analysis using laboratory instruments such as ion chromatographs. This note gives an overview of the technical and organizational points that we identify as critical because we claim that such practical considerations are generally missing in the literature in order to provide guidelines for the successful implementation of future projects running such or similar field-laboratory setups. We share the main stages in the deployment of this tool in the field, the difficulties encountered and the proposed solutions. Our two main conclusions for a successful, long-term functioning of these types of field laboratories are, first, the necessity to adapt several central components of the field laboratory to the local conditions (climate, river geometry, topography, physico-chemical characteristics of water, power supply) and, second, the need of diverse and in-depth technical skills within the engineering team. The critical aspects discussed here relate to (1) supply of the field laboratory – basic functioning of the pumping, filtration and analytical systems; (2) data quality control and assurance via maintenance services and operations; (3) data harmonization and coordination of the laboratory components; and (4) team structure, skills and organization. We believe that sharing these experiences, combined with providing some practical suggestions, might be useful for colleagues who are starting to deploy such or similar field laboratories. These considerations will save time, improve performance and ensure continuous field monitoring.

Stream water chemistry at catchment outlets is commonly used to infer flow paths of water through catchments and to quantify the relative contributions of various flow paths and/or end-members, especially during storm events. For this purpose, the number and nature of these flow paths or end-members are commonly determined with principal component analysis based on all available conservative solute data in inverse end-member mixing analyses (EMMAs). However, apart from the selection of conservative solutes, little attention is paid to the number and choice of the solutes that are included in the analysis, despite the impact this choice can have on the interpretation of the results from an inverse EMMA. Here, we propose a methodology that tries to fill this gap. For a given pair of measured solutes, the proposed methodology determines the minimum number of required end-members, based on the synchronous variation of the solutes during storm events. This allows identification of solute pairs for which a simple two-end-member mixing model is sufficient to explain their variation during storm events and of solute pairs, which show a more complex pattern requiring a higher-order end-member mixing model. We analyse the concentration–concentration relationships of several major ion pairs on the storm-event scale, using multi-year, high-frequency (< 60 min) monitoring data from the outlet of two small (0.8 to 5 km2) French catchments with contrasting land use, climate, and geology. A large number of storm events (56 % to 79 %) could be interpreted as being the result of a mixture of only two end-members, depending on the catchment and the ion pairs used. Even though some of these results could have been expected (e.g. a two-end-member model for the Na+/Cl- pair in a catchment close to the Atlantic coast), others were more surprising and in contrast to previous studies. These findings might help to revise or improve perceptual catchment understanding of flow path or end-member contributions and of biogeochemical processes. In addition, this methodology can identify which solute pairs are governed by identical hydro-biogeochemical processes and which solutes are modified by more complex and diverse processes.