Trends in the epidemiology of catheter-related bloodstream infections; towards a paradigm shift, Spain, 2007 to 2019

Altres ajuts: Departament de Salut. Generalitat de Catalunya ("Pla estratègic de recerca i innovació en salut (PERIS) 2019-2021"); Ministerio de Asuntos Económicos y Transformación Digital; Red Española de Investigación en Patología Infecciosa (REIPI).Background: Catheter-related bloodstream infections (CRBSI) are frequent healthcare-associated infections and an important cause of death. Aim: To analyse changes in CRBSI epidemiology observed by the Infection Control Catalan Programme (VINCat). Methods: A cohort study including all hospital-acquired CRBSI episodes diagnosed at 55 hospitals (2007-2019) in Catalonia, Spain, was prospectively conducted. CRBSI incidence rates were adjusted per 1,000patientdays. To assess the CRBSI rate trend per year, negative binomial models were used, with the number of events as the dependent variable, and the year as the main independent variable. From each model, the annual rate of CRBSI diagnosed per 1,000patientdays and the incidence rate ratio (IRR) with its 95% confidence intervals (CI) were reported. Results: During the study, 9,290 CRBSI episodes were diagnosed (mean annual incidence rate:0.20episodes/1,000patientdays). Patients' median age was 64.1years; 36.6% (3,403/9,290) were female. In total, 73.7% (n=6,845) of CRBSI occurred in non-intensive care unit (ICU) wards, 62.7% (n=5,822) were related to central venous catheter (CVC), 24.1% (n=2,236) to peripheral venous catheters (PVC) and 13.3% (n=1,232) to peripherally-inserted central venous catheters (PICVC). Incidence rate fell over the study period (IRR:0.94;95%CI:0.93-0.96), especially in the ICU (IRR:0.88;95%CI:0.87-0.89). As a whole, while episodes of CVC CRBSI fell significantly (IRR:0.88;95%CI:0.87-0.91), peripherally-inserted catheter CRBSI (PVC and PICVC) rose, especially in medical wards (IRR PICVC:1.08;95%CI:1.05-1.11; IRR PVC: 1.03; 95% 1.00-1.05). Conclusions: Over the study, CRBSIs associated with CVC and diagnosed in ICUs decreased while episodes in conventional wards involving peripherally-inserted catheters increased. Hospitals should implement preventive measures in conventional wards

Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001). Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situatio

Endemic pemphigus foliaceus (fogo selvagem) and pemphigus vulgaris: immunoglobulin G heterogeneity detected by indirect immunofluorescence Pênfigo foliáceo endêmico (fogo selvagem) e pênfigo vulgar: heterogeneidade da imunoglobulina G detectada através da imunofluorescência indireta

Pemphigus are autoimmune intraepidermal blistering diseases in which immunoglobulin G (IgG) autoantibodies are directed against desmosomal glycoproteins. The aim of this study was to determine the IgG subclass profile of endemic pemphigus foliaceus (fogo selvagem) and pemphigus vulgaris utilizing indirect immunofluorescence. PATIENTS AND METHODS: Twenty-five patients with pemphigus vulgaris, 25 with endemic pemphigus foliaceus (fogo selvagem), and 25 healthy controls were analyzed by indirect immunofluorescence for circulating autoantibodies (total IgG and its subclasses). RESULTS: Our data revealed a significant correlation (P <.05) of disease activity and autoantibody levels in both forms of pemphigus, i.e., negative titers related to clinical remission, whereas positive results related to active disease. Immunoglobulin G subclass analysis in fogo selvagem demonstrated that in patients in remission, 56% showed positive immunoglobulin G4; in active disease, immunoglobulin G4 was the predominant subclass (100% positive in all cases). The IgG subclass profile in pemphigus vulgaris showed that in patients in remission, only 10% were positive for immunoglobulin G4; in active disease, positivity for immunoglobulin G4 was present in 78% to 88% of the cases. CONCLUSION: Subclass characterization of immunoglobulin G autoantibodies is a useful tool for pemphigus follow-up, since immunoglobulin G4 (IgG4) is the subclass that is closely related to recognition of pathogenic epitopes, and consequently with disease activity. Careful monitoring should be performed for fogo selvagem in clinical remission with a homogeneous IgG4 response, since this may indicate more frequent relapses.<br>Pênfigos são enfermidades auto-imunes bolhosas intraepidérmicas, onde auto-anticorpos IgG se dirigem contra glicoproteínas desmossomais. O objetivo deste estudo foi determinar o perfil de subclasses de imunoglubulina G no pênfigo foliáceo endêmico (fogo selvagem) e no pênfigo vulgar através da imunofluorescência indireta. MÉTODOS: Vinte e cinco doentes de pênfigo foliáceo endêmico (fogo selvagem), 25 de pênfigo vulgar e 25 controles sadios foram analisados através da imunofluorescência indireta, com respeito aos auto-anticorpos circulantes (imunoglobulina G total e subclasses). RESULTADOS: Nossos dados mostram uma correlação estatisticamente significativa (p<0.05) entre atividade da doença e títulos de auto-anticorpos circulantes em ambas as formas de pênfigo, ou seja, títulos negativos relacionaram-se com remissão clínica, enquanto resultados positivos correlacionaram-se com doença em atividade. A análise de subclasses de IgG mostrou que 56% dos doentes de fogo selvagem em remissão apresentaram apenas IgG4 positiva; na doença ativa, IgG4 foi a subclasse predominante, sendo positiva em 100% dos casos. Nos doentes de pênfigo vulgar, apenas 10% dos doentes em remissão apresentaram positividade exclusiva para IgG4; na doença em atividade, IgG4 esteve presente em 78-83,3% dos casos. CONCLUSÕES: A caracterização de subclasses de imunoglobulina G consiste em um instrumento de grande valia no seguimento de doentes de pênfigo, uma vez que a IgG4 é a subclasse intimamente relacionada com o reconhecimento de epítopos patogênicos, e consequentemente com atividade da enfermidade. No fogo selvagem em remissão com uma resposta homogênea 'as custas de IgG4, uma monitoração cuidadosa deve ser realizada, uma vez que isto pode significar uma maior chance de reativação

Role of Knowledge Management in Development and Lifecycle Management of Biopharmaceuticals

The final publication is available at Springer via https://doi.org/10.1007/s11095-016-2043-9.Knowledge Management (KM) is a key enabler for achieving quality in a lifecycle approach for production of biopharmaceuticals. Due to the important role that it plays towards successful implementation of Quality by Design (QbD), an analysis of KM solutions is needed. This work provides a comprehensive review of the interface between KM and QbD-driven biopharmaceutical production systems as perceived by academic as well as industrial viewpoints. A comprehensive set of 356 publications addressing the applications of KM tools to QbD-related tasks were screened and a query to gather industrial inputs from 17 major biopharmaceutical organizations was performed. Three KM tool classes were identified as having high relevance for biopharmaceutical production systems and have been further explored: knowledge indicators, ontologies, and process modeling. A proposed categorization of 16 distinct KM tool classes allowed for the identification of holistic technologies supporting QbD. In addition, the classification allowed for addressing the disparity between industrial and academic expectations regarding the application of KM methodologies. This is a first of a kind attempt and thus we think that this paper would be of considerable interest to those in academia and industry that are engaged in accelerating development and commercialization of biopharmaceuticals.Industrial Methods for Process Analytical Chemistry - From Measurement Technologies to Information Systems (imPACts