Aging Adults and Seasonal Influenza: Does the Vitamin D Status (H)Arm the Body?

Vitamin D (VitD), although originally described as an essential hormone for bone and mineral homeostasis, appears to have an active role in regulating specific facets of human immunity. Indeed, VitD has been shown to have significant effects on cytokine production and lymphocyte proliferation. Evidence that VitD affects clearance of selected pathogens is supported by epidemiological and clinical data, while its coadministration with influenza vaccine in mice enhanced both mucosal and systemic antibody responses. This paper aims to examine how VitD may contribute to limiting the burden of influenza infection in the aging and aged adults, a population in which this burden remains considerable. Furthermore, we discuss how VitD status may play a role in host resistance to influenza virus and influence the immunogenicity of the influenza vaccines currently licensed for adults aged 65 years or over by its effects on innate and adaptive immunities

Interventions to restore appropriate immune function in the elderly

Advanced age is one indicator of likely immune dysfunction. As worldwide, the global population contains progressively more and more older individuals there is likelihood of an increased prevalence and incidence of infectious diseases due to common and emergent pathogens. The resultant increase in mortality and morbidity would be matched by the risk of functional decline and disability. Maintaining immune function at a plateau throughout life may therefore be associated with considerable cost savings. The aim of improving immune function in older individuals may be achieved through considering a therapeutic approach to rejuvenate, stimulate or support the indigenous immune system to perform in a more optimal manner. In terms of cost effectiveness a therapeutic approach may prove difficult because of issues associated with; identifying those who would benefit the most from this treatment, identifying the type of treatment which would suit them and identifying whether the treatment was successful. The alternative of supporting or providing a stronger stimulus through vaccination, whilst more cost effective, may be a more valuable option in the short term. Both approaches will be addressed in this review

Potentially inappropriate prescribing including under-use amongst older patients with cognitive or psychiatric co-morbidities

Objective: the study aimed to determine the prevalence of and risk factors for inappropriate prescribing (IP) and prescribing omission (PO) in elderly with mental co-morbidities. Participants: one hundred fifty consecutive inpatients with mental co-morbidities hospitalised for acute medical illness (mean age 80 ± 9, 70% of women) were considered for the study. Measurements: IP and PO were prospectively indentified according to STOPP/START criteria at hospital admission. Results: over 95% were taking ≥1 medication (median = 7) which amounted to 1,137 prescriptions. The prevalence of IP was 77% and PO was 65%. The most frequent encountered IP concerned drugs adversely affecting fallers (25%) and antiaggregants therapy without atherosclerosis (14%). PO concerned antidepressants with moderate/severe depression (20%) and calcium-vitamin D supplementation (18%). Independent predictors for IP were increased number of concomitant drugs (odds ratio [OR] 1.54, 95% confidence interval [CI] 1.13-1.89), being cognitively impaired (OR 1.83, 95% CI 1.55-2.24), and having fallen in the preceding 3 months (OR 2.03, 95% CI 1.52-2.61) or hospitalised in the preceding year (OR 1.09, 95% CI 1.02-1.23). Concerning PO, psychiatric disorder (OR 1.64, 95% CI 1.42-2.01) and increase level of co-morbidities (OR 1.79, 95% CI 1.48-1.99) were identified. Living in an institutional setting was a predictive maker for both IP (OR 1.45, 95% CI 1.27-1.74) and PO (OR 1.67, 95% CI 1.32-1.91). Conclusion: IP and PO were highly prevalent raising the need of a greater health literacy concerning geriatric conditions in non-geriatrician practitioners who care elderly as well as in the community, in hospital and institutional settings for improving quality and safety in prescribing medicatio

Effectiveness of influenza vaccine in aging and older adults: comprehensive analysis of the evidence

Foremost amongst the diseases preventable by vaccination is influenza. Worldwide, influenza virus infection is associated with serious adverse events leading to hospitalization, debilitating complications, and death in elderly individuals. Immunization is considered to be the cornerstone for preventing these adverse health outcomes, and vaccination programs are timed to optimize protection during the annual influenza season. Trivalent inactivated influenza virus vaccines are believed to be both effective and cost-saving; however, in spite of widespread influenza vaccination programs, rates of hospitalization for acute respiratory illness and cardiovascular diseases have been increasing in this population during recent annual influenza seasons. From meta-analyses summarizing estimates of influenza vaccine effectiveness from available observational clinical studies, this review aims to examine how effective current influenza vaccine strategies are in the aging and older adult population and to analyze which are the most important biases that interfere with measurements of influenza vaccine effectiveness. Furthermore, consideration is given to strategies that should be adopted in order to optimize influenza vaccine effectiveness in the face of immune exhaustion

Pulmonary delivery of Interleukin 7 provides efficient and safe delivery to the aging immune system

Age-associated atrophy of the thymus with coincident reduction in thymopoeisis, decline in thymic output, and subsequent immune dysfunction has been reversed by the use of interleukin-7 (IL-7). In the earlier studies and in clinical trials, delivery of IL-7 has been by multiple injections over several days to maintain effective activity levels in the tissues. This is unlikely to meet with high compliance rates in future clinical use, and so we tested alternate routes of delivery using a technique involving tagging IL-7 with fluorescent dye that emits in the near-infrared region and whose fluorescence can be visualized within the tissues of live animals. We have shown that intratracheal instillation, enabling transfer through the lungs, provides an effective route for delivering IL-7 into the bloodstream and from there into the tissues in older animals. Delivery is rapid and widespread tissue distribution is seen. Comparison of administration either subcutaneously or by instillation reveals that IL-7 delivery by the pulmonary route provides significantly greater transmission to lymphoid tissues when compared with injection. In functional assessment studies, pulmonary administration led to significantly improved intrathymic T cell development in older animals when compared with IL-7 delivered by injection. Furthermore, in these older animals, delivery of IL-7 by intratracheal instillation was not accompanied by any apparent adverse events when compared with controls receiving saline vehicle by instillation or animals receiving IL-7 by subcutaneous injection

Practical residue curve map analysis applied to solvent recovery in non-ideal binary mixtures by batch distillation processes

Batch distillation inherent advantages has initiated recent search for process feasibility rules enabling the separation of azeotropic or difficult zeotropic binary mixtures thanks to the addition of an entrainer. A systematic procedure enabling to find suitable process and eventually suitable entrainer for the separation of zeotropic or azeotropic binary mixture is described. It brings together into practical use batch distillation process feasibility rules, chemical affinity insight and thermodynamic data analysis available in the literature. The procedure has been implemented in a wizard computer tool and is illustrated on the separation of the water – acetonitrile binary homoazeotrope. Through this tool, all possible 224 feasibility rules and 326 batch distillation sequence processes are checked systematically for each entrainer

The Hospital Anxiety and Depression Scale: low sensitivity for depression screening in demented and non-demented hospitalized elderly

Background: We currently use the depression subscale (HADD) of the Hospital Anxiety and Depression Scale (HADS) for depression screening in elderly inpatients. Given recent concerns about the performance of the HADD in this age group, we performed a quality-control study retrospectively comparing HADD with the diagnosis of depression by a psychiatrist. We also studied the effect of dementia on the scale's performance. Methods: HADS produces two 7-item subscales assessing depression or anxiety. The HADD was administered by a neuropsychologist. As "gold standard” we considered the psychiatrist's diagnosis based on the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria. Patients older than 65 years, assessed by both the HADD and the psychiatrist, with a clinical dementia rating (CDR) score lower than 3, were included. The effect of dementia was assessed by forming three groups according to the CDR score (CDR0-0.5, CDR1, and CDR2). Simple and multiple logistic regression models were applied to predict the psychiatrist's depression diagnosis from HADD scores. Areas under the receiver operating characteristics curve (AUC) were plotted and compared by χ2 tests. Results: On both univariate and multiple analyses, HADD predicted depression diagnosis but performed poorly (univariate: p = 0.009, AUC = 0.60 (95% confidence interval (CI) = 0.53-0.66); multiple: p = 0.007, AUC = 0.65 (95% CI = 0.58-0.71)), regardless of cognitive status. Because mood could have changed between the two assessments (they occurred at different points of the hospital stay), the multiple analyses were repeated after limiting time interval at 28, 21, and 14 days. No major improvements were noted. Conclusion: The HADD performed poorly in elderly inpatients regardless of cognitive status. It cannot be recommended in this population for depression screening without further stud

Incidence and main factors associated with early unplanned hospital readmission among French medical inpatients aged 75 and over admitted through emergency units

Background: among elderly patients, readmission in the month following hospital discharge is a frequent occurrence which involves a risk of functional decline, particularly among frail subjects. While previous studies have identified risk factors of early readmission, geriatric syndromes, as markers of frailty have not been assessed as potential predictors. Objective: to evaluate the risk of early unplanned readmission, and to identify predictors in inpatients aged 75 and over, admitted to medical wards through emergency departments. Design: prospective multi-centre study. Setting: nine French hospitals. Subjects: one thousand three hundred and six medical inpatients, aged 75 and older admitted through emergency departments (SAFES cohort). Methods: using logistic regressions, factors associated with early unplanned re-hospitalisation (defined as first unplanned readmission in the thirty days after discharge) were identified using data from the first week of hospital index stay obtained by comprehensive geriatric assessment. Results: data from a thousand out of 1,306 inpatients were analysed. Early unplanned readmission occurred in 14.2% of inpatients and was not related with sociodemographic characteristics, comorbidity burden or cognitive impairment. Pressure sores (OR=2.05, 95% CI = 1.0-3.9), poor overall condition (OR = 2.01, 95% CI = 1.3-3.0), recent loss of ability for self-feeding (OR = 1.9, 95% CI = 1.2-2.9), prior hospitalisation during the last 3 months (OR = 1.6, 95% CI = 1.1-2.5) were found to be risk factors, while sight disorders appeared as negatively associated (OR = 0.5, 95% CI = 0.3--0.8). Conclusions: markers of frailty (poor overall condition, pressure sores, prior hospitalisation) or severe disability (for self-feeding) were the most important predictors of early readmission among elderly medical inpatients. Early identification could facilitate preventive strategies in risk grou

Automatic Detection of Adverse Drug Events in Geriatric Care: Study Proposal

BACKGROUND One-third of older inpatients experience adverse drug events (ADEs), which increase their mortality, morbidity, and health care use and costs. In particular, antithrombotic drugs are among the most at-risk medications for this population. Reporting systems have been implemented at the national, regional, and provider levels to monitor ADEs and design prevention strategies. Owing to their well-known limitations, automated detection technologies based on electronic medical records (EMRs) are being developed to routinely detect or predict ADEs. OBJECTIVE This study aims to develop and validate an automated detection tool for monitoring antithrombotic-related ADEs using EMRs from 4 large Swiss hospitals. We aim to assess cumulative incidences of hemorrhages and thromboses in older inpatients associated with the prescription of antithrombotic drugs, identify triggering factors, and propose improvements for clinical practice. METHODS This project is a multicenter, cross-sectional study based on 2015 to 2016 EMR data from 4 large hospitals in Switzerland: Lausanne, Geneva, and Zürich university hospitals, and Baden Cantonal Hospital. We have included inpatients aged ≥65 years who stayed at 1 of the 4 hospitals during 2015 or 2016, received at least one antithrombotic drug during their stay, and signed or were not opposed to a general consent for participation in research. First, clinical experts selected a list of relevant antithrombotic drugs along with their side effects, risks, and confounding factors. Second, administrative, clinical, prescription, and laboratory data available in the form of free text and structured data were extracted from study participants' EMRs. Third, several automated rule-based and machine learning-based algorithms are being developed, allowing for the identification of hemorrhage and thromboembolic events and their triggering factors from the extracted information. Finally, we plan to validate the developed detection tools (one per ADE type) through manual medical record review. Performance metrics for assessing internal validity will comprise the area under the receiver operating characteristic curve, F$_{1}$-score, sensitivity, specificity, and positive and negative predictive values. RESULTS After accounting for the inclusion and exclusion criteria, we will include 34,522 residents aged ≥65 years. The data will be analyzed in 2022, and the research project will run until the end of 2022 to mid-2023. CONCLUSIONS This project will allow for the introduction of measures to improve safety in prescribing antithrombotic drugs, which today remain among the drugs most involved in ADEs. The findings will be implemented in clinical practice using indicators of adverse events for risk management and training for health care professionals; the tools and methodologies developed will be disseminated for new research in this field. The increased performance of natural language processing as an important complement to structured data will bring existing tools to another level of efficiency in the detection of ADEs. Currently, such systems are unavailable in Switzerland. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID) DERR1-10.2196/40456