Comparative complete scheme and booster effectiveness of COVID-19 vaccines in preventing SARS-CoV-2 infections with SARS-CoV-2 Omicron (BA.1) and Delta (B.1.617.2) variants: A case-case study based on electronic health records.

Background: Information on vaccine effectiveness in a context of novel variants of concern (VOC) emergence is of key importance to inform public health policies. This study aimed to estimate a measure of comparative vaccine effectiveness between Omicron (BA.1) and Delta (B.1.617.2 and sub-lineages) VOC according to vaccination exposure (primary or booster). Methods: We developed a case-case study using data on RT-PCR SARS-CoV-2-positive cases notified in Portugal during Weeks 49-51, 2021. To obtain measure of comparative vaccine effectiveness, we compared the odds of vaccination in Omicron cases versus Delta using logistic regression adjusted for age group, sex, region, week of diagnosis, and laboratory of origin. Results: Higher odds of vaccination were observed in cases infected by Omicron VOC compared with Delta VOC cases for both complete primary vaccination (odds ratio [OR] = 2.1; 95% confidence interval [CI]: 1.8 to 2.4) and booster dose (OR = 5.2; 95% CI: 3.1 to 8.8), equivalent to reduction of vaccine effectiveness from 44.7% and 92.8%, observed against infection with Delta, to -6.0% (95% CI: 29.2% to 12.7%) and 62.7% (95% CI: 35.7% to 77.9%), observed against infection with Omicron, for complete primary vaccination and booster dose, respectively. Conclusion: Consistent reduction in vaccine-induced protection against infection with Omicron was observed. Complete primary vaccination may not be protective against SARS-CoV-2 infection in regions where Omicron variant is dominant.

Comparative Effectiveness of COVID-19 Vaccines in Preventing Infections and Disease Progression from SARS-CoV-2 Omicron BA.5 and BA.2, Portugal.

We estimated comparative primary and booster vaccine effectiveness (VE) of SARS-CoV-2 Omicron BA.5 and BA.2 lineages against infection and disease progression. During April-June 2022, we implemented a case-case and cohort study and classified lineages using whole-genome sequencing or spike gene target failure. For the case-case study, we estimated the adjusted odds ratios (aORs) of vaccination using a logistic regression. For the cohort study, we estimated VE against disease progression using a penalized logistic regression. We observed no reduced VE for primary (aOR 1.07 [95% CI 0.93-1.23]) or booster (aOR 0.96 [95% CI 0.84-1.09]) vaccination against BA.5 infection. Among BA.5 case-patients, booster VE against progression to hospitalization was lower than that among BA.2 case-patients (VE 77% [95% CI 49%-90%] vs. VE 93% [95% CI 86%-97%]). Although booster vaccination is less effective against BA.5 than against BA.2, it offers substantial protection against progression from BA.5 infection to severe disease.

Tracking SARS-CoV-2 lineage B.1.1.7 dissemination: insights from nationwide spike gene target failure (SGTF) and spike gene late detection (SGTL) data, Portugal, week 49 2020 to week 3 2021.

We show that the SARS-CoV-2 B.1.1.7 lineage is highly disseminated in Portugal, with the odds of B.1.1.7 proportion increasing at an estimated 89% (95% confidence interval: 83-95%) per week until week 3 2021. RT-PCR spike gene target late detection (SGTL) can constitute a useful surrogate to track B.1.1.7 spread, besides the spike gene target failure (SGTF) proxy. SGTL/SGTF samples were associated with statistically significant higher viral loads, but not with substantial shift in age distribution compared to non-SGTF/SGTL cases.

Implementation and impact of an audit and feedback antimicrobial stewardship intervention in the orthopaedics department of a tertiary-care hospital: a controlled interrupted time series study.

A prospective audit and feedback antimicrobial stewardship intervention conducted in the Orthopaedics Department of a university hospital in Portugal was evaluated by comparing an interrupted time series in the intervention group with a non-intervention (control) group. Monthly antibiotic use (except cefazolin) was measured as the World Health Organization's Anatomical Therapeutic Chemical defined daily doses (ATC-DDD) from January 2012 to September 2016, excluding the 6-month phase of intervention implementation starting on 1 January 2015. Compared with the control group, the intervention group had a monthly decrease in the use of fluoroquinolones by 2.3 DDD/1000 patient-days [95% confidence interval (CI) -3.97 to -0.63]. An increase in the use of penicillins by 103.3 DDD/1000 patient-days (95% CI 47.42 to 159.10) was associated with intervention implementation, followed by a decrease during the intervention period (slope = -5.2, 95% CI -8.56 to -1.82). In the challenging scenario of treatment of osteoarticular and prosthetic joint infections, an audit and feedback intervention reduced antibiotic exposure and spectrum.

A disruptive Big data approach to leverage the efficiency in management and clinical decision support in a Hospital.

There is an urgent need to potentiate evidence-based clinical-decision-making with a holistic, patient-centered approach to value, one that focuses both on health-care spending and treatment outcomes.1 On the other hand, in the era of self-driven vehicles, computer systems in healthcare need also to become proactive and to identify relevant clinical patterns in a much faster and automated way than currently used solutions enable. Although this is the state-of-the-art paradigm, in fact, technical constraints block further developments in these areas as hospitals lack the skills to really manage and take value from the big amount of Data about their patients that is stored in dozens of heterogeneous information systems, from lab results to imaging studies, from pharmacy to the Electronic Medical Record (EMR). At São João Hospital Center (São João), a novel analytics platform was conceived, a new approach that is able to leverage all the Big Data that is stored about hospital patients in seconds and to apply some of the most advanced and lightening speed analytics on top of this information in order to empower clinicians and to give them a new decision support tool. This sets the road towards a data-driven hospital of the future, where Data Analytics and Data Science can become as important as the most recent Harrison's edition. With this analytics platform, São João was able to be the first Non-Us institution to ever win the Microsoft U.S Worldwide Innovation Award (HIMSS - Florida, 2014) and the European Big Data & Analytics solution of the year (IT EUROPA - London, 2014). This solution is called HVITAL (Hospital surVeiIlance, moniToring and ALert) and is working 24/7 at São João Hospital since 2012.

[The Impact of Electronic Monitoring on Healthcare Associated Infections: The Role of the HViTAL Platform]. / O Impacto da Monitorização Eletrónica nas Infeções Associadas aos Cuidados de Saúde: O Papel da Plataforma HViTAL.

INTRODUCTION: In Portugal, 9.8% of patients admitted were inflicted with healthcare associated infections, corresponding to a prevalence of 11.7%. The Hospital de São João has developed a business intelligence platform able to supervise (the patients), monitor (the clinical condition) and notify (the healthcare personnel): HViTAL. This study aims to assess the impact of electronic monitoring on healthcare associated infections since the year of HViTAL implementation. MATERIAL AND METHODS: We evaluated data since January 2008 (moment from which computerized records exist) until December 2011, comparing them with subsequent data, those corresponding to January 2012 (implementation date of HViTAL) until 19 October 2015. RESULTS: There was an upward trend of infection parameters in the 2008 - 2011 period. Since January 2012 and October 2015, all parameters of the infection indicator showed a negative linear trend. DISCUSSION: The results are very suggestive that the HVITAL may have had an impact on improving parameters associated to healthcare associated infections. Basic measures of infection control were highlighted since 2005, with an increasing number of health professional awareness campaigns, a fact which, although not analyzed in this report, may also have contributed to the observed improvement. Our study did not include other variables such as investment in human capital. CONCLUSION: There was a clear improvement in all areas characterizing the healthcare associated infections, with obvious positive impact with the introduction of HViTAL.

Introdução: Em Portugal, 9,8% dos doentes internados adquiriram infeções associadas aos cuidados de saúde, correspondendo a uma prevalência de cerca 11,7%. O Centro Hospitalar de São João desenvolveu uma plataforma de business intelligence capaz de VIgiar (os utentes), moniTorizar (o estado clínico) e ALertar (o profissional de saúde): HViTAL. Este estudo tem como objectivo avaliar o impacto da monitorização eletrónica nas infeções associadas aos cuidados de saúde desde o ano da implementação do HViTAL. Material e Métodos: Avaliaram-se os dados relativos a janeiro 2008 (data a partir da qual há registos informatizados) até dezembro de 2011, comparando-os com os dados posteriores, aqueles correspondentes a janeiro de 2012 (data de implementação do HViTAL) até 19 de outubro de 2015. Resultados: Observou-se uma tendência para o aumento dos parâmetros de infecção no período 2008 - 2011. No período correspondente a janeiro de 2012 e outubro de 2015, todos os parâmetros que constituem o indicador de infeção (previsto na contratualização) revelaram uma evolução linear negativa. Discussão: Os resultados são muito sugestivos de que o HVITAL poderá ter tido impacto na melhoria dos parâmetros associados às infeções associadas aos cuidados de saúde. Houve uma tendência crescente na aplicação de medidas básicas de controlo de infecção desde 2005, com ações de sensibilização dos profissionais de saúde, facto que, embora não analisado neste report, poderá também ter contribuído para a melhoria observada. O nosso estudo não incluiu outras variáveis tais como investimento em capital humano. Conclusão: Houve uma inequívoca melhoria em todos os domínios que caracterizam as infeções associadas aos cuidados de saúde, sugerindo um impacto positivo da introdução do HVITAL.

Application of a nitric oxide sensor in biomedicine.

In the present study, we describe the biochemical properties and effects of nitric oxide (NO) in intact and dysfunctional arterial and venous endothelium. Application of the NO electrochemical sensor in vivo and in vitro in erythrocytes of healthy subjects and patients with vascular disease are reviewed. The electrochemical NO sensor device applied to human umbilical venous endothelial cells (HUVECs) and the description of others NO types of sensors are also mentioned.

Comparing several equations that predict peak VO2 using the 20-m multistage-shuttle run-test in 8-10-year-old children.

This study compared the validity of reported equations as predictors of peak VO(2) in 8-10-year-old children. Participants (90 boys and girls aged 8-10 years) performed the multistage-shuttle-run-test (MSRT) and peak VO(2) was measured in field using a portable gas analyser. The equations that estimated peak VO(2) from the MSRT performance were chosen according to the age range of this study. As follows, the FITNESSGRAM reports and the equations of Leger et al. (Can J Appl Sport Sci 5: 77-84, 1988), Barnett et al. (Pediatr Exerc Sci 5:42-50, 1993), Matsuzaka et al. (Pediatr Exerc Sci 16:113-125, 2004) and Fernhall et al. (Am J Ment Retard 102:602-612, 1998) were used to estimate the peak VO(2) and compared with the directly measured value. The equation of Leger et al. (Can J Appl Sport Sci 5: 77-84, 1988) provided a mean difference (d) of 4.7 ml kg(-1) min(-1) and a 1.0 slope. The equation of Matsuzaka et al. (Pediatr Exerc Sci 16:113-125, 2004)(a) using maximal speed (MS) showed a higher d (5.4) than the remaining using total laps d (4.2). The equation of Barnett et al. (Pediatr Exerc Sci 5:42-50, 1993)(a) that includes triceps skinfold and MS showed the highest d (6.1) but the smallest range (24.1) and slope (0.6). Data from the FITNESSGRAM had the smallest d (1.8 ml kg(-1) min(-1)), but also had the highest range between limits of agreement (28.6 ml kg(-1) min(-1)) and a 1.2 slope. The lowest slope (0.4) and range (22.2 ml kg(-1) min(-1)) were observed using the equation of Fernhall et al. (Am J Ment Retard 102:602-612, 1998). Log transformation of the data revealed that the equations of Matsuzaka et al. (Pediatr Exerc Sci 16:113-125, 2004)(a) (1.1*/÷1.25) and Fernhall et al. (Am J Ment Retard 102:602-612, 1998) (1.17*/÷1.25) showed the closest agreement among all, but they still yield unsatisfactory accuracy.

Home telemonitoring of non-invasive ventilation decreases healthcare utilisation in a prospective controlled trial of patients with amyotrophic lateral sclerosis.

BACKGROUND: Non-invasive ventilation (NIV) is an efficient method for treating respiratory failure in patients with amyotrophic lateral sclerosis (ALS). However, it requires a process of adaptation not always achieved due to poor compliance. The role of telemonitoring of NIV is not yet established. OBJECTIVES: To test the advantage of using modem communication in NIV of ALS patients. DESIGN: Prospective, single blinded controlled trial. Population and methods According to their residence, 40 consecutive ventilated ALS patients were assigned to one of two groups: a control group (G1, n=20) in which compliance and ventilator parameter settings were assessed during office visits; or an intervention group (G2, n=20) in which patients received a modem device connected to the ventilator. The number of office and emergency room visits and hospital admissions during the entire span of NIV use and the number of parameter setting changes to achieve full compliance were the primary outcome measurements. RESULTS: Demographic and clinical features were similar between the two groups at admission. No difference in compliance was found between the groups. The incidence of changes in parameter settings throughout the survival period with NIV was lower in G2 (p<0.0001) but it was increased during the initial period needed to achieve full compliance. The number of office or emergency room visits and inhospital admissions was significantly lower in G2 (p<0.0001). Survival showed a trend favouring G2 (p=0.13). CONCLUSIONS: This study shows that telemonitoring reduces health care utilisation with probable favourable implications on costs, survival and functional status.

Redox thiol status plays a central role in the mobilization and metabolism of nitric oxide in human red blood cells.

We assessed the redox thiol status influence on nitric oxide (NO) metabolism and efflux in erythrocytes stimulated with acetylcholinesterase substrate (acetylcholine, ACh) and inhibitor (velnacrine maleate, VM). Erythrocyte suspensions from healthy donors were incubated with increasing concentrations of dithiothreitol (1-50microM), in the presence and absence of acetylcholine/velnacrine (10microM). Levels of NO, nitrite/nitrate, S-nitrosohemoglobin, peroxynitrite and S-nitrosoglutathione were determined by spectrofluorimetric and spectrophotometric methods. Dithiothreitol significantly mobilized NO toward nitrite/nitrate and S-nitrosoglutathione, and decreased the amount of NO efflux. Both ACh/VM induce changes on the levels of erythrocyte nitrite/nitrate dependent on the DTT concentration. Higher levels of peroxynitrite and S-nitrosoglutathione were seen with velnacrine in presence of DTT 1 and 50microM. We concluded that dithiothreitol-induced activation of erythrocyte thiol status decreases NO efflux and allows greater intracellular NO mobilization onto different derivative molecules, both in the absence and presence of acetylcholinesterase substrate and inhibitor.

Modulation of hemorheological parameters by the erythrocyte redox thiol status.

BACKGROUND: There is growing knowledge about the association between hemorheological blood disorders and compromised microcirculation in erythrocyte abnormalities. Effects of the non-neuronal cholinergic elements, especially acetylcholinesterase, on the erythrocyte hemorheological parameters were characterized in the past. However, alterations of these parameters have not been studied under the influence of the cellular redox thiol status. METHODS: Aliquots of venous blood from ten healthy male subjects were incubated in vitro with increasing concentrations of a thiol reducer agent (dithiothreitol 1, 10, 50 microM final concentrations) in the presence and absence of acetylcholinesterase substrate (acetylcholine) or inhibitor (velnacrine maleate). The following parameters were determined in all blood samples aliquots: erythrocyte aggregation, erythrocyte deformability and lipid membrane fluidity. Blood smears were performed. RESULTS: Dithiothreitol induces no significant changes on the hemorheological behaviour of human red cells. Upon intracellular thiol stimulation, the presence of AChE effectors (either acetylcholine or velnacrine) decreases erythrocyte aggregation and elongation indexes. CONCLUSION: The addition of DTT to blood samples aliquots, contributing to the redox thiol status, is not directly involved in the modulation of erythrocyte rheological properties. However, upon acetylcholinesterase modulation by its substrate or inhibitor, changes on the hemorheological parameters are triggered by DTT. Associated pharmacological interest is considerable to address the hemorheology-hemostasis-microcirculation triad disorders.

Non-neuronal cholinergic system and signal transduction pathways mediated by band 3 in red blood cells.

BACKGROUND: Non-neuronal acetylcholine (ACh) and acetylcholinesterase (AChE) have been recognized in the past. Vascular ACh has been associated by us with the regulation of microcirculatory flow by modulating nitric oxide (NO) intracellular mobilization, metabolism (NOx) and release from erythrocytes, as well as the glycolytic flux. Velnacrine maleate is a well-known AChE inhibitor which plays a competitive role by decreasing NO-mediated erythrocyte responses. A plausible hypothesis to explain the mechanisms underlying those events hinges on the NO translocation among nitrosylated molecules and phosphorylated/dephosphorylated states of band 3 protein, processed by major tyrosine-kinases (PTK: p72syk, p53/56lyn and p59/61hck) and phosphotyrosine-phosphatases (PTP). METHODS: To assess this hypothesis under the influence of AChE effectors (acetylcholine/velnacrine), blood samples from healthy donors were harvested and Western blot analysis was subsequently used to determine the degree of band 3 phosphorylation, in the presence and absence of PTK/PTP inhibitors. NO and nitrites/nitrates were quantified using an amperometric method and the Griess Reaction, respectively, in erythrocyte suspensions. Measurements of erythrocyte metabolites (2,3-bisphosphoglycerate; glyceraldehyde 3-phosphate dehydrogenase; glucose-6-phosphodehydrogenase; lactate), hemoglobin and cyclic nucleotides were conducted afterwards. RESULTS: Increased levels of phosphorylated-band 3 obtained upon p72syk inhibition suggest p59/61hck and p53/56lyn as secondary involved kinases. As to NO/NOx quantification, in the presence of PTKi we reported higher levels with velnacrine-AChE, as opposed to acetylcholine-AChE. Calpeptin, a PTP inhibitor which triggers full band 3-phosphorylation, led to the opposite NO mobilization, being reinforced by ACh. Oxy-hemoglobin, glyceraldehyde 3-phosphate dehydrogenase and glucose-6-phosphodehydrogenase were found to decrease with ACh, whereas P50, lactate and both cGMP/cAMP happened to increase. CONCLUSION: Changes on human erythrocyte NOx mobilization and metabolic fluxes occur under influence of non-neuronal ACh/AChE, in turn dependent on the degree of band 3-phosphorylation. Since these vascular events may potentially change under pathological conditions, coadjuvant drugs could become accessible in the setting of microcirculation disease.