RESUMO
In 2022, COVID-19 remained the infectious disease at the top of most internal medicine physicians' minds. However, it was not the only infectious disease that was the topic of clinically relevant research that year. This article highlights some important infectious disease evidence unrelated to COVID-19 that was published in 2022. The literature was screened for sound new evidence relevant to internal medicine specialists and subspecialists whose focus of practice is not infectious diseases. The publications highlighted relate to various organisms in different patient populations. One article provides insight into the role of Helicobacter pylori eradication in the treatment of functional dyspepsia. The descriptive epidemiology of bacterial (Staphylococcus aureus) and viral (mpox) infections are the focus of 2 other articles. Several articles address the management of resistant and difficult-to-treat infections: multidrug-resistant gram-negative infections, resistant HIV-1, rifampin-resistant tuberculosis, cryptococcal meningitis, and invasive fungal infection in the setting of neutropenia. Another article provides data on effective HIV preexposure prophylaxis in women, an understudied population. Finally, given the urgent need to reduce inappropriate use of antibiotics, an article on antibiotic stewardship for hospitalized patients with presumed sepsis in a non-intensive care unit setting is also included.
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COVID-19 , Doenças Transmissíveis , Sepse , Infecções Estafilocócicas , Humanos , Feminino , Doenças Transmissíveis/tratamento farmacológico , Infecções Estafilocócicas/microbiologia , Antibacterianos/uso terapêutico , Sepse/tratamento farmacológicoRESUMO
BACKGROUND: It is unclear whether the reporting quality of antiretroviral (ARV) noninferiority (NI) randomized controlled trials (RCTs) has improved since the CONSORT guideline release in 2006. The primary objective of this systematic review was assessing the methodological and reporting quality of ARV NI-RCTs. We also assessed reporting quality by funding source and publication year. METHODS: We searched Medline, Embase, and Cochrane Central from inception to 14 November 2022. We included NI-RCTs comparing ≥2 ARV regimens used for human immunodeficiency virus treatment or prophylaxis. We used the Cochrane Risk of Bias 2.0 tool to assess risk of bias. Screening and data extraction were performed blinded and in duplicate. Descriptive statistics were used to summarize data; statistical tests were 2 sided, with significance defined as P < .05. The systematic review was prospectively registered (PROSPERO CRD42022328586), and not funded. RESULTS: We included 160 articles reporting 171 trials. Of these articles, 101 (63.1%) did not justify the NI margin used, and 28 (17.5%) did not provide sufficient information for sample size calculation. Eighty-nine of 160 (55.6%) reported both intention-to-treat and per-protocol analyses, while 118 (73.8%) described missing data handling. Ten of 171 trials (5.9%) reported potentially misleading results. Pharmaceutical industry-funded trials were more likely to be double-blinded (28.1% vs 10.3%; P = .03) and to describe missing data handling (78.5% vs 59.0%; P = .02). The overall risk of bias was low in 96 of 160 studies (60.0%). CONCLUSIONS: ARV NI-RCTs should improve NI margin justification, reporting of intention-to-treat and per-protocol analyses, and missing data handling to increase CONSORT adherence.
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Infecções por HIV , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Infecções por HIV/tratamento farmacológicoRESUMO
Compelling evidence suggests a contribution of the sink environment to the transmission of opportunistic pathogens from the hospital environment to patients in neonatal intensive care units (NICU). In this study, the distribution of the opportunistic pathogen Serratia marcescens in the sink environment and newborns in a NICU was investigated. More than 500 sink drain and faucet samples were collected over the course of five sampling campaigns undertaken over 3 years. Distribution and diversity of S. marcescens were examined with a modified MacConkey medium and a high-throughput short-sequence typing (HiSST) method. Sink drains were an important reservoir of S. marcescens, with an average of 44% positive samples, whereas no faucet sample was positive. The genotypic diversity of S. marcescens was moderate, with an average of two genotypes per drain, while the spatial distribution of S. marcescens was heterogeneous. The genotypic profiles of 52 clinical isolates were highly heterogeneous, with 27 unique genotypes, of which 71% of isolates were found in more than one patient. S. marcescens acquisition during the first outbreaks was mainly caused by horizontal transmissions. HiSST analyses revealed 10 potential cases of patient-to-patient transmission of S. marcescens, five cases of patient-to-sink transmission, and one bidirectional transfer between sink and patient. Environmental and clinical isolates were found in sink drains up to 1 year after the first detection, supporting persisting drain colonization. This extensive survey suggests multiple reservoirs of S. marcescens within the NICU, including patients and sink drains, but other external sources should also be considered. IMPORTANCE The bacterium Serratia marcescens is an important opportunistic human pathogen that thrives in many environments, can become multidrug resistant, and is often involved in nosocomial outbreaks in neonatal intensive care units (NICU). We evaluated the role of sinks during five suspected S. marcescens outbreaks in a NICU. An innovative approach combining molecular and culture methods was used to maximize the detection and typing of S. marcescens in the sink environment. Our results indicate multiple reservoirs of S. marcescens within the NICU, including patients, sink drains, and external sources. These results highlight the importance of sinks as a major reservoir of S. marcescens and potential sources of future outbreaks.
Assuntos
Infecção Hospitalar , Infecções por Serratia , Humanos , Recém-Nascido , Unidades de Terapia Intensiva Neonatal , Infecção Hospitalar/microbiologia , Serratia marcescens/genética , Infecções por Serratia/epidemiologia , Surtos de DoençasRESUMO
BACKGROUND: Schizophrenia is a disease associated with high burden, and improvement in care is necessary. Artificial intelligence (AI) has been used to diagnose several medical conditions as well as psychiatric disorders. However, this technology requires large amounts of data to be efficient. Social media data could be used to improve diagnostic capabilities. OBJECTIVE: The objective of our study is to analyze the current capabilities of AI to use social media data as a diagnostic tool for psychotic disorders. METHODS: A systematic review of the literature was conducted using several databases (PubMed, Embase, Cochrane, PsycInfo, and IEEE Xplore) using relevant keywords to search for articles published as of November 12, 2021. We used the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) criteria to identify, select, and critically assess the quality of the relevant studies while minimizing bias. We critically analyzed the methodology of the studies to detect any bias and presented the results. RESULTS: Among the 93 studies identified, 7 studies were included for analyses. The included studies presented encouraging results. Social media data could be used in several ways to care for patients with schizophrenia, including the monitoring of patients after the first episode of psychosis. We identified several limitations in the included studies, mainly lack of access to clinical diagnostic data, small sample size, and heterogeneity in study quality. We recommend using state-of-the-art natural language processing neural networks, called language models, to model social media activity. Combined with the synthetic minority oversampling technique, language models can tackle the imbalanced data set limitation, which is a necessary constraint to train unbiased classifiers. Furthermore, language models can be easily adapted to the classification task with a procedure called "fine-tuning." CONCLUSIONS: The use of social media data for the diagnosis of psychotic disorders is promising. However, most of the included studies had significant biases; we therefore could not draw conclusions about accuracy in clinical situations. Future studies need to use more accurate methodologies to obtain unbiased results.
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Transtornos Psicóticos , Esquizofrenia , Mídias Sociais , Inteligência Artificial , Humanos , Transtornos Psicóticos/diagnóstico , Esquizofrenia/diagnóstico , Comportamento SocialRESUMO
Molecular typing methods are used to characterize the relatedness between bacterial isolates involved in infections. These approaches rely mostly on discrete loci or whole-genome sequencing (WGS) analyses of pure cultures. On the other hand, their application to environmental DNA profiling to evaluate epidemiological relatedness among patients and environments has received less attention. We developed a specific, high-throughput short sequence typing (HiSST) method for the opportunistic human pathogen Serratia marcescens. Genes displaying the highest polymorphism were retrieved from the core genome of 60 S. marcescens strains. Bioinformatics analyses showed that use of only three loci (within bssA, gabR, and dhaM) distinguished strains with a high level of efficiency. This HiSST scheme was applied to an epidemiological survey of S. marcescens in a neonatal intensive care unit (NICU). In a first case study, a strain responsible for an outbreak in the NICU was found in a sink drain of this unit, by using HiSST scheme and confirmed by WGS. The HiSST scheme was also applied to environmental DNA extracted from sink-environment samples. Diversity of S. marcescens was modest, with 11, 6, and 4 different sequence types (ST) of gabR, bssA, and dhaM loci among 19 sink drains, respectively. Epidemiological relationships among sinks were inferred on the basis of pairwise comparisons of ST profiles. Further research aimed at relating ST distribution patterns to environmental features encompassing sink location, utilization, and microbial diversity is needed to improve the surveillance and management of opportunistic pathogens. IMPORTANCE Serratia marcescens is an important opportunistic human pathogen, often multidrug resistant and involved in outbreaks of nosocomial infections in neonatal intensive care units. Here, we propose a quick and user-friendly method to select the best typing scheme for nosocomial outbreaks in relating environmental and clinical sources. This method, named high-throughput short sequence typing (HiSST), allows to distinguish strains and to explore the diversity profile of nonculturable S. marcescens. The application of HiSST profile analysis for environmental DNA offers new possibilities to track opportunistic pathogens, identify their origin, and relate their distribution pattern with environmental features encompassing sink location, utilization, and microbial diversity. Adaptation of the method to other opportunistic pathogens is expected to improve knowledge regarding their ecology, which is of significant interest for epidemiological risk assessment and elaborate outbreak mitigation strategies.
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Infecção Hospitalar , DNA Ambiental , Serratia marcescens/classificação , Técnicas de Tipagem Bacteriana , Surtos de Doenças , Humanos , Recém-Nascido , Unidades de Terapia Intensiva NeonatalRESUMO
BACKGROUND: Renal ischemia-reperfusion predisposes to acute kidney injury (AKI) and mortality. APAC, mast cell heparin proteoglycan mimetic is a potent dual antiplatelet and anticoagulant inhibiting thrombosis in several vascular models. METHODS: Clinically relevant (0.06 and 0.13 mg/kg) and high (0.32 and 7.3 mg/kg) heparin doses of APAC and unfractionated heparin (UFH) were administered i.v. in pharmacological studies. Antithrombotic action of APAC and UFH was assessed with platelet aggregation to collagen, activated partial thromboplastin (APTT) and prothrombin (PT) times. Pharmacodynamics of [64Cu]-APAC or -UFH were monitored by PET/CT. Next, APAC and UFH doses (0.06 and 0.13 mg/kg) were i.v. administered 10 min prior to renal ischemia-reperfusion injury (IRI) in rats. RESULTS: APAC in contrast to UFH inhibited platelet aggregation. During 0.06 and 0.13 mg/kg dose regimens APTT and PT remained at baseline, but at the high APTT prolonged fourfold to sixfold. Overall bio-distribution and clearance of APAC and UFH were similar. After bilateral 30-min renal artery clamping, creatinine, urea nitrogen and neutrophil gelatinase-associated lipocalin concentrations and histopathology indicated faster renal recovery by APAC (0.13 mg/kg). APAC, unlike UFH, prevented expression of innate immune ligand hyaluronan and tubulointerstitial injury marker Kim-1. Moreover, in severe bilateral 1-h renal artery clamping, APAC (0.13 mg/kg) prevented AKI, as demonstrated both by biomarkers and survival. Compatible with kidney protection APAC reduced the circulating levels of vascular destabilizing and pro-inflammatory angiopoietin-2 and syndecan-1. No tissue bleeding ensued. CONCLUSION: APAC and UFH were similarly eliminated via kidneys and liver. In contrast to UFH, APAC (0.13 mg/kg) was reno-protective in moderate and even severe IRI by attenuating vascular injury and innate immune activation.
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Injúria Renal Aguda/prevenção & controle , Anticoagulantes/farmacologia , Heparina/análogos & derivados , Heparina/farmacologia , Rim/efeitos dos fármacos , Inibidores da Agregação Plaquetária/farmacologia , Proteoglicanas/farmacologia , Traumatismo por Reperfusão/prevenção & controle , Injúria Renal Aguda/sangue , Injúria Renal Aguda/imunologia , Injúria Renal Aguda/patologia , Proteínas de Fase Aguda , Angiopoietina-2/sangue , Animais , Anticoagulantes/farmacocinética , Biomarcadores/sangue , Biotransformação , Coagulação Sanguínea/efeitos dos fármacos , Nitrogênio da Ureia Sanguínea , Creatinina/sangue , Modelos Animais de Doenças , Quimioterapia Combinada , Heparina/farmacocinética , Ácido Hialurônico/sangue , Imunidade Inata/efeitos dos fármacos , Rim/imunologia , Rim/metabolismo , Rim/patologia , Lipocalina-2 , Lipocalinas/sangue , Masculino , Tempo de Tromboplastina Parcial , Agregação Plaquetária/efeitos dos fármacos , Inibidores da Agregação Plaquetária/farmacocinética , Testes de Função Plaquetária , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Proteoglicanas/farmacocinética , Tempo de Protrombina , Proteínas Proto-Oncogênicas/sangue , Ratos Sprague-Dawley , Traumatismo por Reperfusão/sangue , Traumatismo por Reperfusão/imunologia , Traumatismo por Reperfusão/patologia , Sindecana-1/sangue , Distribuição TecidualRESUMO
BACKGROUND: the literature suggests that simulation is an effective strategy to meet the learning needs of nursing students. Traditionally, simulation learning for nursing students takes place at nursing schools ; at a distance from the clinical setting, patients, and the interprofessional team. AIM: the objective of this pilot project is to explore the experiences of Francophone nursing students following their participation in an interprofessional simulation in a hospital setting during their third year clinical placements. METHOD: a case study using Yin's (2003) approach was used to explore this phenomenon through focus groups and individual interviews. RESULTS: thirteen people participated in three simulation sessions that each included two scenarios. Content analysis of the focus groups revealed four themes : 1) the need for a realistic, but safe environment ; 2) simulation helps to build self-confidence ; 3) simulation improves knowledge of the role of the nurse ; and 4) simulation improves knowledge of teamwork. Two themes emerged from individual interviews : 1) the knowledge and skills acquired during the simulation were retained over time ; and 2) perceptions of the effects on the quality and safety of patient care. CONCLUSION: the use of simulation could be effective for the development of knowledge of nursing role, teamwork, and self-confidence.
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Relações Interprofissionais , Treinamento por Simulação/métodos , Estudantes de Enfermagem/psicologia , Humanos , Aprendizagem , Pesquisa em Educação em Enfermagem , Pesquisa em Avaliação de Enfermagem , Pesquisa Metodológica em Enfermagem , Projetos PilotoRESUMO
Complement protein C1q is induced in the brain in response to a variety of neuronal injuries, including Alzheimer disease (AD), and blocks fibrillar amyloid-ß (fAß) neurotoxicity in vitro. Here, we show that C1q protects immature and mature primary neurons against fAß toxicity, and we report for the first time that C1q prevents toxicity induced by oligomeric forms of amyloid-ß (Aß). Gene expression analysis reveals C1q-activated phosphorylated cAMP-response element-binding protein and AP-1, two transcription factors associated with neuronal survival and neurite outgrowth, and increased LRP1B and G protein-coupled receptor 6(GPR6) expression in fAß-injured neurons. Silencing of cAMP-response element-binding protein, LRP1B or GPR6 expression inhibited C1q-mediated neuroprotection from fAß-induced injury. In addition, C1q altered the association of oligomeric Aß and fAß with neurons. In vivo, increased hippocampal expression of C1q, LRP1B, and GPR6 is observed as early as 2 months of age in the 3 × Tg mouse model of AD, whereas no such induction of LRP1B and GPR6 was seen in C1q-deficient AD mice. In contrast, expression of C1r and C1s, proteases required to activate the classical complement pathway, and C3 showed a significant age-dependent increase only after 10-13 months of age when Aß plaques start to accumulate in this AD model. Thus, our results identify pathways by which C1q, up-regulated in vivo early in response to injury without the coordinate induction of other complement components, can induce a program of gene expression that promotes neuroprotection and thus may provide protection against Aß in preclinical stages of AD and other neurodegenerative processes.
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Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Complemento C1q/metabolismo , Regulação da Expressão Gênica , Receptores Acoplados a Proteínas G/fisiologia , Receptores de LDL/fisiologia , Proteínas Supressoras de Tumor/fisiologia , Animais , Modelos Animais de Doenças , Perfilação da Expressão Gênica , Humanos , Camundongos , Modelos Biológicos , Doenças Neurodegenerativas/metabolismo , Ratos , Receptores Acoplados a Proteínas G/metabolismo , Receptores de LDL/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Regulação para CimaRESUMO
Deficiency in C1q, the recognition component of the classical complement cascade and a pattern recognition receptor involved in apoptotic cell clearance, leads to lupus-like autoimmune diseases characterized by auto-antibodies to self proteins and aberrant innate immune cell activation likely due to impaired clearance of apoptotic cells. In this study, we developed an autologous system using primary human lymphocytes and human monocyte-derived macrophages (HMDMs) to characterize the effect of C1q on macrophage gene expression profiles during the uptake of apoptotic cells. C1q bound to autologous apoptotic lymphocytes modulated expression of genes associated with JAK/STAT signaling, chemotaxis, immunoregulation, and NLRP3 inflammasome activation in LPS-stimulated HMDMs. Specifically, C1q sequentially induced type I IFNs, IL-27, and IL-10 in LPS-stimulated HMDMs and IL-27 in HMDMs when incubated with apoptotic lymphocyte conditioned media. Coincubation with C1q tails prevented the induction of type I IFNs and IL-27 in a dose-dependent manner, and neutralization of type I IFNs partially prevented IL-27 induction by C1q. Finally, C1q decreased procaspase-1 cleavage and caspase-1-dependent cleavage of IL-1ß suggesting a potent inhibitory effect of C1q on inflammasome activation. These results identify specific molecular pathways induced by C1q to suppress macrophage inflammation and provide potential therapeutic targets to control macrophage polarization and thus inflammation and autoimmunity.
Assuntos
Proteínas Reguladoras de Apoptose/fisiologia , Polaridade Celular/imunologia , Complemento C1q/fisiologia , Inflamassomos/imunologia , Macrófagos/imunologia , Caspase 1/metabolismo , Inibidores de Caspase , Adesão Celular/imunologia , Células Cultivadas , Quimiocinas/biossíntese , Citocinas/biossíntese , Humanos , Inflamassomos/antagonistas & inibidores , Interleucina-1beta/metabolismo , Lipopolissacarídeos/metabolismo , Linfócitos/citologia , Linfócitos/imunologia , Macrófagos/citologia , Macrófagos/metabolismoRESUMO
OBJECTIVE: Evaluate the effects of five disinfection methods on bacterial concentrations in hospital sink drains, focusing on three opportunistic pathogens (OPs): Serratia marcescens, Pseudomonas aeruginosa and Stenotrophomonas maltophilia. DESIGN: Over two years, three sampling campaigns were conducted in a neonatal intensive care unit (NICU). Samples from 19 sink drains were taken at three time points: before, during, and after disinfection. Bacterial concentration was measured using culture-based and flow cytometry methods. High-throughput short sequence typing was performed to identify the three OPs and assess S. marcescens persistence after disinfection at the genotypic level. SETTING: This study was conducted in a pediatric hospitals NICU in Montréal, Canada, which is divided in an intensive and intermediate care side, with individual rooms equipped with a sink. INTERVENTIONS: Five treatments were compared: self-disinfecting drains, chlorine disinfection, boiling water disinfection, hot tap water flushing, and steam disinfection. RESULTS: This study highlights significant differences in the effectiveness of disinfection methods. Chlorine treatment proved ineffective in reducing bacterial concentration, including the three OPs. In contrast, all other drain interventions resulted in an immediate reduction in culturable bacteria (4-8 log) and intact cells (2-3 log). Thermal methods, particularly boiling water and steam treatments, exhibited superior effectiveness in reducing bacterial loads, including OPs. However, in drains with well-established bacterial biofilms, clonal strains of S. marcescens recolonized the drains after heat treatments. CONCLUSIONS: Our study supports thermal disinfection (>80°C) for pathogen reduction in drains but highlights the need for additional trials and the implementation of specific measures to limit biofilm formation.
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Desinfecção , Unidades de Terapia Intensiva Neonatal , Serratia marcescens , Serratia marcescens/efeitos dos fármacos , Desinfecção/métodos , Humanos , Pseudomonas aeruginosa/efeitos dos fármacos , Recém-Nascido , Stenotrophomonas maltophilia/efeitos dos fármacos , Infecções por Serratia/microbiologia , Infecções por Serratia/prevenção & controle , Infecção Hospitalar/prevenção & controle , Infecção Hospitalar/microbiologiaRESUMO
BACKGROUND: Advancements in the cystic fibrosis (CF) field have resulted in longer lifespans for individuals with CF. This has led to more responsibility for complex care regimens, frequent health care, and prescription medication utilization that are costly and may not be fully covered by health insurance. There are outstanding questions about unmet medical needs among the U.S. population with CF and how the financial burden of CF is associated with debt, housing instability, and food insecurity. METHODS: Researchers developed the CF Health Insurance Survey (CF HIS) to survey a convenience sample of people living with CF in the U.S. The sample was weighted to reflect the parameters of the 2019 Cystic Fibrosis Foundation Patient Registry Annual Data Report, and chi-square tests and multiple logistic regression models were conducted. RESULTS: A total of 1,856 CF patients in the U.S. were included in the study. Of these, 64% faced a financial burden: 55% of respondents faced debt issues, 26% housing issues, and 33% food insecurity issues. A third reported at least one unmet medical need: 24% faced unmet prescription needs, 12% delayed or shortened a hospitalization, and 10% delayed or skipped a care center visit as a result of the cost of care. CONCLUSIONS: People with CF in the U.S. experience high financial burden, which is associated with unmet medical needs. Income is the biggest risk factor for financial burden for people with CF, with people dually covered by Medicare and Medicaid particularly at risk.
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Fibrose Cística , Medicare , Humanos , Estados Unidos/epidemiologia , Idoso , Habitação , Fibrose Cística/epidemiologia , Fibrose Cística/terapia , Instabilidade Habitacional , Acessibilidade aos Serviços de Saúde , Serviços de Saúde , Insegurança AlimentarRESUMO
Molecular typing techniques are utilized to determine genetic similarities between bacterial isolates. However, the use of environmental DNA profiling to assess epidemiologic links between patients and their environment has not been fully explored. This work reports the development and validation of two high-throughput short sequence typing (HiSST) schemes targeting the opportunistic pathogens Pseudomonas aeruginosa and Stenotrophomonas maltophilia, along with a modified SM2I selective medium for the specific isolation of S. maltophilia. These HiSST schemes are based on four discriminative loci for each species and demonstrate high discriminating power, comparable to pairwise whole-genome comparisons. Each scheme includes species-specific PCR primers for precise differentiation from closely related taxa, without the need for upstream culture-dependent methods. For example, the primers targeting the bvgS locus make it possible to distinguish P. aeruginosa from the very closely related Pseudomonas paraeruginosa sp. nov. The selected loci included in the schemes are adapted to massive parallel amplicon sequencing technology. An R-based script implemented in the DADA2 pipeline was assembled to facilitate HiSST analyses for efficient and accurate genotyping of P. aeruginosa and S. maltophilia. We demonstrate the performance of both schemes through in silico validations, assessments against reference culture collections, and a case study involving environmental samples.
RESUMO
Activation of the complement cascade, a powerful effector mechanism of the innate immune system, is associated with neuroinflammation but also with elimination of inappropriate synapses during development. Synthesis of C1q, a recognition component of the complement system, occurs in brain during ischemia/reperfusion and Alzheimer's disease, suggesting that C1q may be a response to injury. In vitro, C1q, in the absence of other complement proteins, improves neuronal viability and neurite outgrowth and prevents ß-amyloid-induced neuronal death, suggesting that C1q may have a direct neuroprotective role. Here, investigating the molecular basis for this neuroprotection in vitro, addition of C1q to rat primary cortical neurons significantly upregulated expression of genes associated with cholesterol metabolism, such as cholesterol-25-hydroxylase and insulin induced gene 2, and transiently decreased cholesterol levels in neurons, known to facilitate neurite outgrowth. In addition, the expression of syntaxin-3 and its functional association with synaptosomal-associated protein 25 was increased. C1q also increased the nuclear translocation of cAMP response element-binding protein and CCAAT/enhancer-binding protein-δ (C/EBP-δ), two transcription factors involved in nerve growth factor (NGF) expression and downregulated specific microRNAs, including let-7c that is predicted to target (and thus inhibit) NGF and neurotrophin-3 (NT-3) mRNA. Accordingly, C1q increased expression of NGF and NT-3, and small interfering RNA inhibition of C/EBP-δ, NGF, or NT-3 expression prevented the C1q-dependent neurite outgrowth. No such neuroprotective effect is seen in the presence of C3a or C5a. Finally, the induced neuronal gene expression required conformationally intact C1q. These results show that C1q can directly promote neuronal survival, thereby demonstrating new interactions between immune proteins and neuronal cells that may facilitate neuroprotection.
Assuntos
Complemento C1q/fisiologia , Regulação da Expressão Gênica no Desenvolvimento , MicroRNAs/biossíntese , Neurônios/fisiologia , Fármacos Neuroprotetores , Animais , Sobrevivência Celular/imunologia , Células Cultivadas , Regulação da Expressão Gênica no Desenvolvimento/imunologia , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/genética , Neurônios/imunologia , Neurônios/patologia , Ratos , Ratos Sprague-DawleyRESUMO
The objective of the clinical project was to plan and deploy a knowledge translation approach to prevent falls among elderly patients hospitalized in a unit of cardiovascular medicine. A combination of education strategies built around interactive workshops enabled the implementation of a screening tool and of an up-to-date preventive intervention guide. Twenty-four workshops were conducted in all three work shifts and an implementation follow-up was made. The participation rate was 93% of the unit's active staff The increased use of prevention tools and of an intervention guide to prevent falls suggests an increased level of awareness as a result of the project. The staff expressed their satisfaction on having been consulted and involved early in the implementation process. Moreover, the flexible schedule and focus on a bilateral sharing of knowledge through brief interactive workshops were appreciated.
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Acidentes por Quedas/prevenção & controle , Doenças Cardiovasculares/enfermagem , Difusão de Inovações , Capacitação em Serviço , Recursos Humanos de Enfermagem Hospitalar/educação , Idoso , Humanos , QuebequeRESUMO
Consumer cost-sharing has been shown to diminish utilization of preventive services. Recent efforts, including provisions within the Affordable Care Act, have sought to increase use of preventive care through elimination of cost-sharing for clinically indicated services. We conducted a rapid review of the literature to determine the impact of cost-share elimination on utilization of preventive services. Searches were conducted in PubMed, Scopus, and CINAHL Complete databases as well as in grey literature. A total of 35 articles were included in qualitative synthesis and findings were summarized for three clinical service categories: cancer screenings, contraceptives, and additional services. Impacts of cost-sharing elimination varied depending on clinical service, with a majority of findings showing increases in use. Studies that included socioeconomic status reported that those who were financially vulnerable incurred substantial increases in utilization. Future investigations on additional clinical services are warranted as is research to better elucidate populations who most benefit from cost-sharing elimination.
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Custo Compartilhado de Seguro , Patient Protection and Affordable Care Act , Bases de Dados Factuais , Detecção Precoce de Câncer , Humanos , Serviços Preventivos de Saúde , Estados UnidosRESUMO
BACKGROUND: SARS-CoV-2 transmission has an impact on education. In this study, we assessed the performance of rapid antigen detection tests (RADTs) versus polymerase chain reaction (PCR) for the diagnosis of SARS-CoV-2 infection in school settings, and RADT use for monitoring exposed contacts. METHODS: In this real-world, prospective observational cohort study, high-school students and staff were recruited from 2 high schools in Montréal, Canada, and followed from Jan. 25 to June 10, 2021. Twenty-five percent of asymptomatic participants were tested weekly by RADT (nasal) and PCR (gargle). Class contacts of cases were tested. Symptomatic participants were tested by RADT (nasal) and PCR (nasal and gargle). The number of cases and outbreaks were compared with those of other high schools in the same area. RESULTS: Overall, 2099 students and 286 school staff members consented to participate. The overall specificity of RADTs varied from 99.8% to 100%, with a lower sensitivity, varying from 28.6% in asymptomatic to 83.3% in symptomatic participants. Secondary cases were identified in 10 of 35 classes. Returning students to school after a 7-day quarantine, with a negative PCR result on days 6-7 after exposure, did not lead to subsequent outbreaks. Of cases for whom the source was known, 37 of 51 (72.5%) were secondary to household transmission, 13 (25.5%) to intraschool transmission, and 1 to community contacts between students in the same school. INTERPRETATION: Rapid antigen detection tests did not perform well compared with PCR in asymptomatic individuals. Reinforcing policies for symptom screening when entering schools and testing symptomatic individuals with RADTs on the spot may avoid subsequent substantial exposures in class. Preprint: medRxiv - doi.org/10.1101/2021.10.13.21264960.
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COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , Estudos de Coortes , Sistemas Automatizados de Assistência Junto ao Leito , Estudos Prospectivos , COVID-19/diagnóstico , COVID-19/epidemiologiaRESUMO
BACKGROUND: Complement proteins and activation products have been found associated with neuropathology in Alzheimer's disease (AD). Recently, a C5a receptor antagonist was shown to suppress neuropathology in two murine models of AD, Tg2576 and 3xTg. Previously, a genetic deficiency of C1q in the Tg2576 mouse model showed an accumulation of fibrillar plaques similar to the complement sufficient Tg2576, but reactive glia were significantly decreased and neuronal integrity was improved suggesting detrimental consequences for complement activation in AD. The goal of this study was to define the role of the classical complement activation pathway in the progression of pathology in the 3xTg mouse that develops tangles in addition to fibrillar plaques (more closely reflecting human AD pathology) and to assess the influence of complement in a model of AD with a higher level of complement hemolytic activity. METHODS: 3xTg mice deficient in C1q (3xTgQ-/-) were generated, and both 3xTg and 3xTgQ-/- were backcrossed to the BUB mouse strain which has higher in vitro hemolytic complement activity. Mice were aged and perfused, and brain sections stained for pathological markers or analyzed for proinflammatory marker expression. RESULTS: 3xTgQ-/- mice showed similar amounts of fibrillar amyloid, reactive glia and hyperphosphorylated tau as the C1q-sufficient 3xTg at the ages analyzed. However, 3xTg and 3xTgQ-/- on the BUB background developed pathology earlier than on the original 3xTg background, although the presence of C1q had no effect on neuropathological and pro-inflammatory markers. In contrast to that seen in other transgenic models of AD, C1q, C4 and C3 immunoreactivity was undetectable on the plaques of 3xTg in any background, although C3 was associated with reactive astrocytes surrounding the plaques. Importantly, properdin a component of the alternative complement pathway was associated with plaques in all models. CONCLUSIONS: In contrast to previously investigated transgenic models of AD, development of neuropathology in 3xTg mice, which progresses much slower than other murine models, may not be influenced by fibrillar amyloid mediated activation of the classical complement pathway, suggesting that the alternative complement pathway activation or a C3-independent cleavage of C5 could account for the detrimental effects in these mice that are prevented by the C5a receptor antagonist. Furthermore, the paucity of complement activation may be a factor in the slower kinetics of progression of pathology in the 3xTg model of this disease.
Assuntos
Doença de Alzheimer/imunologia , Doença de Alzheimer/patologia , Encéfalo/imunologia , Encéfalo/patologia , Ativação do Complemento , Modelos Animais de Doenças , Doença de Alzheimer/fisiopatologia , Precursor de Proteína beta-Amiloide/metabolismo , Animais , Biomarcadores/metabolismo , Feminino , Humanos , Fatores Imunológicos/imunologia , Masculino , Camundongos , Camundongos Transgênicos , Properdina/imunologia , Proteínas tau/genética , Proteínas tau/metabolismoRESUMO
RATIONALE: The short-term prognosis of pulmonary embolism (PE) depends on hemodynamic status and underlying disease. The prognostic value of right ventricular dysfunction and injury is less well established. OBJECTIVES: To evaluate prognostic factors of PE in a multicenter prospective cohort study. METHODS: Echocardiography, brain natriuretic peptide (BNP), N-terminal-proBNP and cardiac troponin I measurements were done on admission of 570 consecutive patients with an acute PE. A predictive model was based on independent predictors of 30-day adverse events defined as death, secondary cardiogenic shock, or recurrent venous thromboembolism. MEASUREMENTS AND MAIN RESULTS: At 30 days, 42 patients (7.4%; 95% confidence interval [CI], 5.5-9.8%) had adverse events. On multivariate analysis, altered mental state (odds ratio [OR] 6.8; 95% confidence interval [CI], 2.0-23.3), shock on admission (OR 2.8; 95% CI, 1.1-7.5), cancer (OR 2.9; 95% CI, 1.2-6.9), BNP (OR 1.3 for an increase of 250 ng/L; 95% CI, 1.1-1.6) and right to left ventricle diameter ratio (OR 1.2 for an increase of 0.1; 95% CI, 1.1-1.4) were associated with 30-days of adverse events. The predictive performance of the model was good (area under receiver operating characteristics curve 0.84 [95% CI, 0.78-0.90]), making it possible to develop a bedside prognostic score. CONCLUSIONS: BNP and echocardiography may be useful determinants of the short-term outcome for patients with PE, together with clinical findings. Patients with PE can be stratified according to the initial risk of adverse outcome, using a simple score based on clinical, echocardiographic, and biochemical variables.
Assuntos
Embolia Pulmonar/genética , Embolia Pulmonar/fisiopatologia , Doença Aguda , Idoso , Causas de Morte , Estudos de Coortes , Ecocardiografia , Feminino , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Estatísticos , Análise Multivariada , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Prognóstico , Estudos Prospectivos , Recidiva , Medição de Risco , Choque Cardiogênico/mortalidade , Choque Cardiogênico/fisiopatologia , Taxa de Sobrevida , Troponina I/sangue , Tromboembolia Venosa/mortalidade , Tromboembolia Venosa/fisiopatologiaRESUMO
Since the introduction of routine assay for natriuretic peptides (NP), there is an increasing number of clinical applications for these assays. Due to the continuously increasing number of prescription of those tests, a reappraisal of the use of natriuretic peptide assays, namely BNP and NT-proBNP in France was necessary. This was achieved through a national survey to obtain a detailed description of NP prescription and realization by French laboratories. A questionnaire was sent in April 2010 to hospital and private clinical chemists. Statistical analysis of results concerned 584 answers. This survey demonstrated an equivalent use of BNP and NT-proBNP both in public or private laboratories together with a huge heterogeneity of tests used within labs. Medical prescription heterogeneity both in public or private sectors confirms the large implication of those tests in clinical diagnosis. These assays are not yet standardized, so clinicians and biologists should be very careful when interpreting the results for diagnostic or therapeutic monitoring.
Assuntos
Técnicas de Diagnóstico Endócrino/estatística & dados numéricos , Peptídeos Natriuréticos/análise , Coleta de Dados , Técnicas de Diagnóstico Endócrino/instrumentação , Testes Diagnósticos de Rotina/instrumentação , Testes Diagnósticos de Rotina/métodos , Testes Diagnósticos de Rotina/estatística & dados numéricos , França/epidemiologia , Ensaios de Triagem em Larga Escala/instrumentação , Ensaios de Triagem em Larga Escala/estatística & dados numéricos , Humanos , Laboratórios/estatística & dados numéricos , Padrões de Prática Médica/estatística & dados numéricos , Troponina/análiseRESUMO
Faucet aerators have been linked to multiple opportunistic pathogen outbreaks in hospital, especially Pseudomonas aeruginosa, their complex structure promoting biofilm development. The importance of bacteria aerosolization by faucet aerators and their incidence on the risk of infection remain to be established. In this study, ten different types of aerators varying in complexity, flow rates and type of flow were evaluated in a controlled experimental setup to determine the production of aerosols and the level of contamination. The aerosol particle number density and size distribution were assessed using a particle spectrometer. The bacterial load was quantified with a 14-stage cascade impactor, where aerosol particles were captured and separated by size, then analysed by culture and flow cytometry. The water was seeded with Pseudomonas fluorescens as a bacterial indicator. Aerosol particle size and mean mass distribution varied depending on the aerator model. Devices without aeration or with laminar flow produced the lowest number and mass of aerosol particles when measured with spectrometry. Models with aeration displayed wide differences in their potential production of aerosol particles. A new aerator with a low flow, no air inlet in its structure, and a spray stream produced 12 to 395 times fewer aerosol particles containing bacteria. However, the impact of low flow on biofilm development and incorporation of pathogens should be further investigated. Repeated use of aerators resulted in fouling which increased the quantity of bacteria released through aerosol particles. An in-depth mechanical cleaning including complete dismantling of the aerator was required to recover initial performances. Aerators should be selected to minimize aerosol production, considering the ease of maintenance and the main water usage at each sink. Low flow aerators produced a lower number of contaminated aerosol particles when new but may be more susceptible to fouling and quickly lose their initial advantage.