Aplicabilidade da média das forças musculares respiratórias como parte da escala de risco cirúrgico baseada na escala de Torrington e Henderson

ObjectiveEvaluate the applicability of mean percentage from the predicted value of respiratory muscle strength (maximal inspiratory pressure-MIP; maximal expiratory pressure-MEP), as (% MIP + % MEP)/2, as well as the peak expiratory flow (% PEF) preoperatively, as part of a surgical risk scale for predicting the risk of postoperative pulmonary complications (PPC). MethodData on patients undergoing elective surgery of chest, abdomen and limbs were assessed preoperatively using the items and the scoring system proposed by the Torrington and Henderson, and replacing spirometry by the mean values of both (% MIP + % MEP)/2 and % PEF. ResultThe proposed scale applied to 108 patients with a mean age of 55.2 ± 14.0 presented PPC rate of 37.0% (p = 0.0001), of which 20.0% were classified as high risk (HR), and 62.5% moderate risk (MR). The mean value of respiratory muscle strength showed a statistically significant correlation with PPC (p = 0.000). ConclusionThe proposed scale allowed the appropriate stratification of patients at risk for development of PPC. The use of the mean values of (% MIP + % MEP)/2 and % PEF based on the predicted values can be easily applied, making spirometry unnecessary.ObjetivoAvaliar a aplicabilidade da média do percentual do valor predito das forças musculares respiratórias (pressão inspiratória máxima-PImax; pressão expiratória máxima-PEmax), sendo % PImax + % PEmax/2, e do pico de fluxo expiratório (% PFE) no pré-operatório, como parte de uma escala de risco cirúrgico para predizer o risco de complicação pulmonar pós-operatória (CPP). MétodoDados de pacientes submetidos à cirurgia eletiva de tórax, abdômen e membros foram analisados no pré-operatório utilizando os itens e a pontuação proposta pela escala de Torrington e Henderson, e substituindo a espirometria pela média do % PImax + % PEmax / 2 e do % PFE. ResultadoNa escala proposta aplicada a 108 pacientes com idade média de 55,2 ± 14,0 a taxa de CPP foi de 37,0% (p = 0,0001), onde 20,0% foram classificados como de alto risco (RA) e 62,5% risco moderado (RM). O percentual da média da força muscular respiratória apresentou uma correlação significante em relação à CPP na escala proposta (p = 0,000). ConclusãoA escala proposta permitiu estratificar de maneira adequada pacientes com risco de CPP. A utilização da média do % PImax + % PEmax / 2 e do % PFE, baseados nos valores preditos, podem ser facilmente aplicáveis, tornando-se desnecessária a realização da espirometria.Federal University of São Paulo Paulista Medical SchoolUniversity of Northern ParanáIrmandade da Santa Casa de LondrinaUniversity of Northern Paraná Hospital PhysiotherapyHospital Zona SulUNIFESP, EPMSciEL

Comparative efficacy and safety of pharmacological interventions for managing sickle cell disease complications in children and adolescents: a systematic review with network meta-analyses

Objectives: Sickle cell disease (SCD), an inherited hemoglobinopathy that causes anemia, severe pain, and vaso-occlusive crisis (VOC), is currently recognized as a global public health concern, being the leading cause of pediatric stroke. Our aim was to synthesize the evidence on the efficacy and safety of interventions for managing SCD in this population. Methods: A systematic review with searches in PubMed, Scopus, and Web of Science was performed (April-2022). Randomized controlled trials comparing disease-modifying agents in SCD patients under 18 years old were included. For each outcome of interest, data were pooled by means of Bayesian network meta-analyses with the surface under the cumulative ranking curve analyses (SUCRA). Results were reported as odds ratio (OR) with 95% credibility intervals (CrI). Results: Seventeen trials (1982-2022) mostly from African countries (65%) and North America (53%), assessing the effect of different interventions’ regimens (hydroxyurea [n=6 trials], L-arginine [n=3], antiplatelets [n=2], immunotherapy/monoclonal antibodies [n=2], sulfates [n=2], docosahexaenoic acid [n=1], niprisan [n=1]) and placebo were included. No statistical differences among treatments were found for the main outcomes. SUCRA revealed that immunotherapy/monoclonal antibodies and hydroxyurea 20 mg/kg are potentially more effective against acute chest syndrome (83% and 76% probabilities, respectively), VOC (71% and 80%, respectively) and needing of transfusions (72% and 75%, respectively), while L-arginine (100-200 mg/kg) and placebo were more prone to these events. Although therapies were overall considered safe, antiplatelet and sulfates may lead to more discontinuations and severe adverse events (uncertainty evidence). Results were similar between age subgroups (<10 years vs. 10-19 years). Conclusions: The available evidence on the effect of drugs on managing SCD in children and adolescents is insufficient and weak. No clear definition for some outcomes exists. Hydroxyurea may remain the standard of care for this population, however, long-term well-designed, and well-reported trials comparing new immunotherapy/monoclonal antibodies should be performed.info:eu-repo/semantics/publishedVersio

Efficacy and safety of pharmacological interventions for managing sickle cell disease in children and adolescents: protocol for a systematic review with network meta-analysis

IntroductionSickle cell disease (SCD), an inherited haemoglobinopathy, has important impact on morbidity and mortality, especially in paediatrics. Previous systematic reviews are limited to adult patients or focused only on few therapies. We aim to synthesise the evidence on efficacy and safety of pharmacological interventions for managing SCD in children and adolescents.Methods and analysisThis systematic review protocol is available at Open Science Framework (doi:10.17605/OSF.IO/CWAE9). We will follow international recommendations on conduction and report of systematic reviews and meta-analyses. Searches will be conducted in PubMed, Scopus and Web of Science (no language nor time restrictions) (first pilot searches performed in May 2022). We will include randomised controlled trials comparing the effects of disease-modifying agents in patients with SCD under 18 years old. Outcomes of interest will include: vaso-occlusive crisis, haemoglobin levels, chest syndrome, stroke, overall survival and adverse events. We will provide a narrative synthesis of the findings, and whenever possible, results will be pooled by means of pairwise or Bayesian network meta-analyses with surface under the cumulative ranking curve analyses. Different statistical methods and models will be tested. Dichotomous outcomes will be reported as OR, risk ratio or HR, while continuous data will be reported as standard mean differences, both with 95% CI/credibility interval. The methodological quality of the trials will be evaluated using the Risk of Bias 2.0 tool, and the certainty of the evidence will be assessed with the Grading of Recommendations Assessment, Development and Evaluation approach.Ethics and disseminationThis study refers to a systematic review, so no ethics approval is necessary. We intent to publish our findings in international, peer-reviewed journal. Data will also be presented to peers in scientific events. Additionally, the results obtained in this study may contribute towards the update of therapeutic guidelines and for the development of health policies for SCD.PROSPERO registration numberCRD42022328471.</jats:sec

The role of benralizumab in eosinophilic immune dysfunctions: a case report-based literature review

In the past years, the knowledge of eosinophils playing a primary pathophysiologic role in several associated conditions has led to the development of biologics targeting therapies aiming at normalizing the immune response, reducing chronic inflammation, and preventing tissue damage. To better illustrate the potential relationship between different eosinophilic immune dysfunctions and the effects of biological therapies in this scenario, here, we present a case of a 63-year-old male first referred to our department in 2018 with a diagnosis of asthma, polyposis, and rhinosinusitis and presenting a suspicion of nonsteroidal anti-inflammatory drugs' allergy. He also had a past medical history of eosinophilic gastroenteritis/duodenitis (eosinophilia counts >50 cells/high-power field HPF). The use of multiple courses of corticosteroid therapy failed to completely control these conditions. In October 2019, after starting benralizumab (an antibody directed against the alpha chain of the IL-5 cytokine receptor) as an add-on treatment for severe eosinophilic asthma, important clinical improvements were reported both in the respiratory (no asthma exacerbations) and gastrointestinal systems (eosinophilia count 0 cells/HPF). The patient's quality of life also increased. Since June 2020, systemic corticosteroid therapy was reduced without worsening gastrointestinal symptoms or eosinophilic inflammation. This case warns of the importance of early recognition and appropriate individualized treatment of eosinophilic immune dysfunctions and suggests the conduction of further larger studies on the use of benralizumab in gastrointestinal syndromes aiming at better understanding its relying mechanisms of action in the intestinal mucosa.info:eu-repo/semantics/publishedVersio

Lag times in the publication of network meta-analyses: A survey

Objective We assessed the extent of lag times in the publication and indexing of network meta-analyses (NMAs). Study design This was a survey of published NMAs on drug interventions. Setting NMAs indexed in PubMed (searches updated in May 2020). Primary and secondary outcome measures Lag times were measured as the time between the last systematic search and the article submission, acceptance, online publication, indexing and Medical Subject Headings (MeSH) allocation dates. Time-to-event analyses were performed considering independent variables (geographical origin, Journal Impact Factor, Scopus CiteScore, open access status) (SPSS V.24, R/RStudio). Results We included 1245 NMAs. The median time from last search to article submission was 6.8 months (204 days (IQR 95-381)), and to publication was 11.6 months. Only 5% of authors updated their search after first submission. There is a very slightly decreasing historical trend of acceptance (rho=-0.087; p=0.010), online publication (rho=-0.080; p=0.008) and indexing (rho=-0.080; p=0.007) lag times. Journal Impact Factor influenced the MeSH allocation process, but not the other lag times. The comparison between open access versus subscription journals confirmed meaningless differences in acceptance, online publication and indexing lag times. Conclusion Efforts by authors to update their search before submission are needed to reduce evidence production time. Peer reviewers and editors should ensure authors' compliance with NMA standards. The accuracy of these findings depends on the accuracy of the metadata used; as we evaluated only NMA on drug interventions, results may not be generalisable to all types of studies

a nationwide Portuguese consensus

Introduction and objectives: We aimed to build a national consensus to optimize the use of oral corticosteroids (OCS) in severe asthma in Portugal. Material and methods: A modified 3-round Delphi including 65 statements (topics on chronic systemic corticotherapy, therapeutic schemes, asthma safety and monitoring) was performed via online platform (October-November 2019). A five-point Likert-type scale was used (1-‘strongly disagree’; 5-‘strongly agree’). Consensus threshold was established as a percentage of agreement among participants ≥90% in the 1st round and ≥85% in the 2nd and 3rd rounds. The level of consensus achieved by the panel was discussed with the participants (face-to-face meeting). Results: Forty-eight expert physicians in severe asthma (specialists in allergology and pulmonology) participated in the study. Almost half of the statements (28/65; 43.1%) obtained positive consensus by the end of round one. By the end of the exercise, 12 (18.5%) statements did not achieve consensus. Overall, 87% of physicians agree that further actions for OCS cumulative risk assessment in acute asthma exacerbations are needed. The vast majority (91.7%) demonstrated a favorable perception for using biological agents whenever patients are eligible. Most participants (95.8%) are more willing to accept some degree of lung function deterioration compared to other outcomes (worsening of symptoms, quality of life) when reducing OCS dose. Monitoring patients’ comorbidities was rated as imperative by all experts. Conclusions: : These results can guide an update on asthma management in Portugal and should be supplemented by studies on therapy access, patients’ adherence, and costs.publishersversionpublishe

Pharmacovigilance: an evaluation on the practice of pharmacists acting in pharmacies and drugstores

Pharmacists acting in pharmacies and drugstores stores are some of the most accessible healthcare providers and the last to intervene before the patient takes their medicine. This puts the pharmacist in a position of authority that should be harnessed for the benefit of health. Thus, this professional is strategic for performing pharmacovigilance. Our objective of this study was to interrogate the practice of pharmacists in relation to pharmacovigilance activities, and to identify difficulties and possible stimuli for the improvement these activities in pharmacies and drugstores. The information was collected through an online questionnaire via Survey Monkey®. The data were analyzed statistically using SPSS software. Responses were received from 5174 pharmacists: mostly young women within five years of graduation and experience in pharmaceutical retail. 81% of them reported having identified suspected substandard medicines, but only 16% used the Brazilian notification system Notivisa. More than 85% of pharmacists agreed with the importance of pharmacovigilance and the recognition of reporting services as part of pharmacist duties and pharmaceutical care. The main barriers to making notifications were the lack of access and knowledge about Notivisa. Pharmacists agreed that simplifying the system would be a stimulus for notifications, and requested more feedback from notifications, as well as material and courses to understand the notification process. Pharmacists have important data to feed into pharmacovigilance systems, recognize their responsibilities and are willing to contribute, but still demonstrate low compliance. Simplification of the system and training on it are likely to increase notifications

Use of biochemical tests and machine learning in the search for potential diagnostic biomarkers of COVID-19, HIV/AIDS, and pulmonary tuberculosis

The authors express their gratitude to the Brazilian National Council of Technological and Scientific Development (CNPq) and CAPES (Brazilian Federal Agency for Support and Evaluation of Graduate Education within the Ministry of Education of Brazil) for research funding - Finance Code 001.This study aims to develop, validate, and evaluate machine learning algorithms for predicting the diagnosis of coronavirus disease (COVID-19), human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS), pulmonary tuberculosis (TB), and HIV/TB co-infection. We also investigated potential biomarkers associated with the diagnosis. Data from biochemical and hematological tests of infected and controls were collected in a single general hospital, totalizing 6,418 patients. The discriminant analysis by partial least squares (PLS-DA) model had the highest performance in predicting the diagnosis of COVID-19, HIV/AIDS, TB, and HIV/TB co-infection with an accuracy of 94, 97, 95, and 96%, respectively. The biomarkers calcium, lactate dehydrogenase, red blood cells (RBC), white blood cells, neutrophils, basophils, eosinophils, hemoglobin, and hematocrit were associated with COVID-19. HIV infection was associated with mean corpuscular volume, platelets, neutrophils, and mean platelet volume. Red blood cell distribution width and urea were associated with infection by Mycobacterium tuberculosis. The following biomarkers were associated with HIV/TB co-infection: lymphocytes, RBC, hematocrit, hemoglobin, aspartate transaminase, alanine transaminase, and glycemia. The PLS-DA model can optimize COVID-19, HIV/AIDS, TB, and HIV/TB co-infection diagnostics. Some biomarkers were potential diagnostic indicators and could be evaluated during the screening of these diseases.info:eu-repo/semantics/publishedVersio

Systematic review and evidence gap mapping of biomarkers associated with neurological manifestations in patients with COVID-19

Objective: This study aimed to synthesize the existing evidence on biomarkers related to coronavirus disease 2019 (COVID-19) patients who presented neurological events. Methods: A systematic review of observational studies (any design) following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines and the Cochrane Collaboration recommendations was performed (PROSPERO: CRD42021266995). Searches were conducted in PubMed and Scopus (updated April 2023). The methodological quality of nonrandomized studies was assessed using the Newcastle‒Ottawa Scale (NOS). An evidence gap map was built considering the reported biomarkers and NOS results. Results: Nine specific markers of glial activation and neuronal injury were mapped from 35 studies published between 2020 and 2023. A total of 2,237 adult patients were evaluated in the included studies, especially during the acute phase of COVID-19. Neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) biomarkers were the most frequently assessed (n = 27 studies, 77%, and n = 14 studies, 40%, respectively). Although these biomarkers were found to be correlated with disease severity and worse outcomes in the acute phase in several studies (p < 0.05), they were not necessarily associated with neurological events. Overall, 12 studies (34%) were judged as having low methodological quality, 9 (26%) had moderate quality, and 9 (26%) had high quality. Conclusions: Different neurological biomarkers in neurosymptomatic COVID-19 patients were identified in observational studies. Although the evidence is still scarce and conflicting for some biomarkers, well-designed longitudinal studies should further explore the pathophysiological role of NfL, GFAP, and tau protein and their potential use for COVID-19 diagnosis and management.info:eu-repo/semantics/publishedVersio

Optimizing the use of systemic corticosteroids in severe asthma (ROSA II project): a national Delphi consensus study

Although the prevalence of severe asthma is not high (5–10% of patients), it is responsible for a large part of the overall disease burden and costs (50–60% of total costs), especially if the condition remains uncontrolled (which occurs in around 40% of cases). Currently, for patients without disease control or presenting frequent exacerbations despite optimal therapy, add-on treatments, traditionally long-acting anticholinergics, oral corticosteroids (OCS), or biologic agents (monoclonal antibodies) are recommended. Nonetheless, the long-term use of oral/systemic corticosteroids (CS) is significantly associated with adverse effects, acute and chronic complications that may decrease health-related quality of life and worsen prognosis, thus requiring additional monitoring and management. Conversely, target therapies (i.e., omalizumab, mepolizumab, reslizumab, benralizumab, and more recently, dupilumab) have been developed grounded on the different phenotypes and endotypes of severe asthma, and are gradually reducing the reliance on OCS (i.e., greater specificity for achieving disease control by reducing the risk of exacerbations and requirements for rescue medication and OCS, with limited adverse events).This work was supported by AstraZeneca.info:eu-repo/semantics/publishedVersio