The Role of Multidimensional Prognostic Index to Identify Hospitalized Older Adults with COVID-19 Who Can Benefit from Remdesivir Treatment: An Observational, Prospective, Multicenter Study

Background: Data regarding the importance of multidimensional frailty to guide clinical decision making for remdesivir use in older patients with coronavirus disease 2019 (COVID-19) are largely unexplored. Objective: The aim of this research was to evaluate if the Multidimensional Prognostic Index (MPI), a multidimensional frailty tool based on the Comprehensive Geriatric Assessment (CGA), may help physicians in identifying older hospitalized patients affected by COVID-19 who might benefit from the use of remdesivir. Methods: This was a multicenter, prospective study of older adults hospitalized for COVID-19 in 10 European hospitals, followed-up for 90 days after hospital discharge. A standardized CGA was performed at hospital admission and the MPI was calculated, with a final score ranging between 0 (lowest mortality risk) and 1 (highest mortality risk). We assessed survival with Cox regression, and the impact of remdesivir on mortality (overall and in hospital) with propensity score analysis, stratified by MPI = 0.50. Results: Among 496 older adults hospitalized for COVID-19 (mean age 80 years, female 59.9%), 140 (28.2% of patients) were treated with remdesivir. During the 90 days of follow-up, 175 deaths were reported, 115 in hospital. Remdesivir treatment significantly reduced the risk of overall mortality (hazard ratio [HR] 0.54, 95% confidence interval CI 0.35–0.83 in the propensity score analysis) in the sample as whole. Stratifying the population, based on MPI score, the effect was observed only in less frail participants (HR 0.47, 95% CI 0.22–0.96 in propensity score analysis), but not in frailer subjects. In-hospital mortality was not influenced by remdesivir use. Conclusions: MPI could help to identify less frail older adults hospitalized for COVID-19 who could benefit more from remdesivir treatment in terms of long-term survival

Association between dispatch of mobile stroke units and functional outcomes among patients with acute ischemic stroke in Berlin

Importance Effects of thrombolysis in acute ischemic stroke are time-dependent. Ambulances that can administer thrombolysis (mobile stroke units [MSUs]) before arriving at the hospital have been shown to reduce time to treatment. Objective To determine whether dispatch of MSUs is associated with better clinical outcomes for patients with acute ischemic stroke. Design, Setting, and Participants This prospective, nonrandomized, controlled intervention study was conducted in Berlin, Germany, from February 1, 2017, to October 30, 2019. If an emergency call prompted suspicion of stroke, both a conventional ambulance and an MSU, when available, were dispatched. Functional outcomes of patients with final diagnosis of acute cerebral ischemia who were eligible for thrombolysis or thrombectomy were compared based on the initial dispatch (both MSU and conventional ambulance or conventional ambulance only). Exposure Simultaneous dispatch of an MSU (computed tomographic scanning with or without angiography, point-of-care laboratory testing, and thrombolysis capabilities on board) and a conventional ambulance (n = 749) vs conventional ambulance alone (n = 794). Main Outcomes and Measures The primary outcome was the distribution of modified Rankin Scale (mRS) scores (a disability score ranging from 0, no neurological deficits, to 6, death) at 3 months. The coprimary outcome was a 3-tier disability scale at 3 months (none to moderate disability; severe disability; death) with tier assignment based on mRS scores if available or place of residence if mRS scores were not available. Common odds ratios (ORs) were used to quantify the association between exposure and outcome; values less than 1.00 indicated a favorable shift in the mRS distribution and lower odds of higher levels of disability. Results Of the 1543 patients (mean age, 74 years; 723 women [47%]) included in the adjusted primary analysis, 1337 (87%) had available mRS scores (primary outcome) and 1506 patients (98%) had available the 3-tier disability scale assessment (coprimary outcome). Patients with an MSU dispatched had lower median mRS scores at month 3 (1; interquartile range [IQR], 0-3) than did patients without an MSU dispatched (2; IQR, 0-3; common OR for worse mRS, 0.71; 95% CI, 0.58-0.86; P < .001). Similarly, patients with an MSU dispatched had lower 3-month coprimary disability scores: 586 patients (80.3%) had none to moderate disability; 92 (12.6%) had severe disability; and 52 (7.1%) had died vs patients without an MSU dispatched: 605 (78.0%) had none to moderate disability; 103 (13.3%) had severe disability; and 68 (8.8%) had died (common OR for worse functional outcome, 0.73, 95% CI, 0.54-0.99; P = .04). Conclusions and Relevance In this prospective, nonrandomized, controlled intervention study of patients with acute ischemic stroke in Berlin, Germany, the dispatch of mobile stroke units, compared with conventional ambulances alone, was significantly associated with lower global disability at 3 months. Clinical trials in other regions are warranted.This cohort study compares global disability at 3 months among Berlin patients with out-of-hospital ischemic stroke brought to care via a mobile stroke unit ambulance (with prehospital CT scanning with or without angiography, point-of-care laboratory testing, prehospital thrombolysis) vs conventional ambulance alone.Question Is the dispatch of mobile stroke units in the out-of-hospital setting before arriving at the hospital associated with better functional outcomes among patients with acute ischemic stroke eligible for thrombolysis or thrombectomy? Findings In this prospective nonrandomized controlled intervention study involving 1543 patients in Berlin, Germany, the dispatch of mobile stroke units in addition to conventional ambulances vs conventional ambulances alone was significantly associated with lower levels of global disability at 3 months (common odds ratio for higher modified Rankin Scale scores [ie, worse outcome], 0.71). Meaning Among patients with acute ischemic stroke in Berlin, Germany, dispatch of a mobile stroke unit was associated with lower global disability at 3 months; further research in diverse settings is needed.Clinical epidemiolog

Horizontal Career Changes as an Alternative to Premature Exit From Work

Certain workplaces are called jobs with limited tenure. Due to physical or psychosocial risk factors, often coupled with qualification mismatches, workers cannot grow old in them. That may lead to premature exit into retirement, to a period of drawing a work incapacity pension or to a long spell of unemployment. A horizontal career change, which enables the worker to move on to a less burdening workplace while preserving social status, is a possible solution. The objective of the “Horizontal career change—a new job opportunity for older employees” project is to develop a model of career changes for workers employed in jobs with limited tenure and to implement it in the form of an information- and communication technology-based tool. Possible applications range from individual career planning, through institutionalized vocational reintegration, to personnel development in small and medium-sized enterprises

Modular Assembly of HostGuest MetalPhenolic Networks Using Macrocyclic Building Blocks

The manipulation of interfacial properties has broad implications for the development of high-performance coatings. Metalphenolic networks (MPNs) are an emerging class of responsive, adherent materials. Herein, hostguest chemistry is integrated with MPNs to modulate their surface chemistry and interfacial properties. Macrocyclic cyclodextrins (host) are conjugated to catechol or galloyl groups and subsequently used as components for the assembly of functional MPNs. The assembled cyclodextrin-based MPNs are highly permeable (even to high molecular weight polymers: 250500 kDa), yet they specifically and noncovalently interact with various functional guests (including small molecules, polymers, and carbon nanomaterials), allowing for modular and reversible control over interfacial properties. Specifically, by using either hydrophobic or hydrophilic guest molecules, the wettability of the MPNs can be readily tuned between superrepellency (&gt;150°) and superwetting (ca. 0°)

Particle Targeting in Complex Biological Media

Over the past few decades, nanoengineered particles have gained increasing interest for applications in the biomedical realm, including diagnosis, imaging, and therapy. When functionalized with targeting ligands, these particles have the potential to interact with specific cells and tissues, and accumulate at desired target sites, reducing side effects and improve overall efficacy in applications such as vaccination and drug delivery. However, when targeted particles enter a complex biological environment, the adsorption of biomolecules and the formation of a surface coating (e.g., a protein corona) changes the properties of the carriers and can render their behavior unpredictable. For this reason, it is of importance to consider the potential challenges imposed by the biological environment at the early stages of particle design. This review describes parameters that affect the targeting ability of particulate drug carriers, with an emphasis on the effect of the protein corona. We highlight strategies for exploiting the protein corona to improve the targeting ability of particles. Finally, we provide suggestions for complementing current in vitro assays used for the evaluation of targeting and carrier efficacy with new and emerging techniques (e.g., 3D models and flow-based technologies) to advance fundamental understanding in bio-nano science and to accelerate the development of targeted particles for biomedical applications