Ruta assistencial de complexitat 2.0 (PCC/MACA) a Catalunya: definició de la ruta i proposta de desplegament

Ruta assistencial; Pacients crònics complexos; DesplegamentVia clínica; Pacientes crónicos complejos; DespliegueClinical pathway; Complex chronic patients; DeploymentLes rutes assistencials s’orienten a donar una millor resposta a les persones amb patologies i problemes de salut crònics i de més prevalença; permeten millorar-ne el maneig, organitzar l’atenció dels professionals partint d’un model d’atenció integrada i proactiva, adequar la prestació de serveis a un model d’atenció compartida entre els diferents àmbits d’atenció, així com definir mecanismes per a la individualització del pla d’atenció i l’adequació en la utilització de recursos. En aquest document es presenta la ruta assistencial de complexitat (PCC/MACA) i es proporcionen instruments i eines per fer-ne el desplegament al territori

Use of an interactomics pipeline to assess the potential of new antivirals against SARS-CoV-2

(Póster 80) Background: In late 2019 SARS-CoV-2 infection appeared in China, becoming a pandemic in 2020. The scientific community reacted rapidly, characterizing the viral genome and its encoded proteins, aiming at interfering with viral spreading with vaccines and antivirals. The receptor binding domain (RBD) of the viral spike (S) protein plays a key role in cell entry of the virus. It interacts with the cellular receptor for SARS-CoV-2, the membrane-bound human Angiotensin Converting Ectoenzyme 2 (ACE2). With the goal of monitoring interference with this interaction by potential antiviral drugs, we have set up at the Institute for Biomedicine of Valencia (IBV-CSIC) an interactomics pipeline targeting the initial step of viral entry. Methods: For the production part of the pipeline (pure RBD/Spike variants and soluble ACE2), see parallel poster. These proteins allowed monitoring of the RBD/Spike-ACE2 interaction in presence or absence of potential inhibitors. Thermal shift assays (thermofluor) were used for initial detection of compound binding at different ligand/protein ratios and media conditions (pH, buffers, chaotropic agents). Next, binding affinity and on/off kinetics were characterized using Biolayer interferometry (BLI), Surface plasmon resonance (SPR), Microscale Thermophoresis (MST) and/or Isothermal titration calorimetry (ITC). For protein-protein interactions, we mostly used BLI or SPR, whereas for proteinsmall compound analysis MST was generally best. Protein aggregation-dissociation was monitored by size exclusion chromatography with multiangle light scattering (SEC-MALS). Results: Candidates proven by thermal shift assays to bind to RBD/spike protein without affecting the integrity of these proteins were subjected to quantitative affinity measurements. We successfully demonstrated that BLI, SPR and MST can be used to follow the interactions between SARS-CoV- 2 proteins and the putative drug candidates, as well as to monitor the interference with Spike-Ace2 binding of potential drug candidates. While BLI and SPR displayed reproducible results in the measurement of protein-protein interaction (applied to soluble ACE2 used as a decoy), they were less suitable for measuring the binding of small molecules. The fact that most small compounds were only soluble in organic solvents made difficult to obtain a low signal/noise while using BLI, necessary for the assessment of the binding. We overcame that problem by using MST. After dilution of the compounds to the final experimental concentrations, the technique could detect a significant binding signal enough to calculate binding parameters. MST also allowed to measure the degree of interference that each compound was having on RBD/Spike-ACE2 interaction. The pipeline has been customized and validated with compounds of very different nature provided by different groups belonging to the PTI and other external laboratories, as well as with different Ace2 decoys designed at the IBV. Conclusions: The interactomics platform at the IBV has been used to successfully develop two different antiviral approaches in order to fight COVID-19. It has allowed technical specialization of the staff as well as the development, in a very short period of time, of two ambitious projects. We have demonstrated that we can perform interactomic characterization for challenging projects as well as provide information about binding of antivirals to potential new SARS-CoV-2 variants of concern

Is systematic training in opioid overdose prevention effective?

The objectives were to analyze the knowledge about overdose prevention, the use of naloxone, and the number of fatal overdoses after the implementation of Systematic Training in Overdose Prevention (STOOP) program. We conducted a quasi-experimental study, and held face-to-face interviews before (n = 725) and after (n = 722) implementation of systematic training in two different samples of people who injected opioids attending harm reduction centers. We asked participants to list the main causes of overdose and the main actions that should be taken when witnessing an overdose. We created two dependent variables, the number of (a) correct and (b) incorrect answers. The main independent variable was Study Group: Intervention Group (IG), Comparison Group (CG), Pre-Intervention Group With Sporadic Training in Overdose Prevention (PREIGS), or Pre-Intervention Group Without Training in Overdose Prevention (PREIGW). The relationship between the dependent and independent variables was assessed using a multivariate Poisson regression analysis. Finally, we conducted an interrupted time series analysis of monthly fatal overdoses before and after the implementation of systematic program during the period 2006-2015. Knowledge of overdose prevention increased after implementing systematic training program. Compared to the PREIGW, the IG gave more correct answers (IRR = 1.40;95%CI:1.33-1.47), and fewer incorrect answers (IRR = 0.33;95%CI:0.25-0.44). Forty percent of people who injected opioids who received a naloxone kit had used the kit in response to an overdose they witnessed. These courses increase knowledge of overdose prevention in people who use opioids, give them the necessary skills to use naloxone, and slightly diminish the number of fatal opioid overdoses in the city of Barcelon