Knowledge, attitudes and perceptions of Latin American healthcare workers relating to antibiotic stewardship and antibiotic use: a cross-sectional multi-country study.

BACKGROUND: The burden of antimicrobial resistance (AMR) in Latin America is high. Little is known about healthcare workers' (HCWs) knowledge, attitudes, and perceptions of antimicrobial stewardship (AS), AMR, and antibiotic use (AU) in the region. METHODS: HCWs from 42 hospitals from 5 Latin American countries were invited to take an electronic, voluntary, anonymous survey regarding knowledge, attitudes, and perceptions of AS, AMR, and AU between March-April 2023. FINDINGS: Overall, 996 HCWs completed the survey (52% physicians, 32% nurses, 11% pharmacists, 3% microbiologists, and 2% "other"). More than 90% of respondents indicated optimizing AU was a priority at their healthcare facility (HCF), 69% stated the importance of AS was communicated at their HCF, and 23% were unfamiliar with the term "antibiotic stewardship". Most (> 95%) respondents acknowledged that appropriate AU can reduce AMR; however, few thought AU (< 30%) or AMR (< 50%) were a problem in their HCF. Lack of access to antibiogram and to locally endorsed guidelines was reported by 51% and 34% of HCWs, respectively. Among prescribers, 53% did not consider non-physicians' opinions to make antibiotic-related decisions, 22% reported not receiving education on how to select antibiotics based on culture results and 60% stated patients and families influence their antibiotic decisions. CONCLUSIONS: Although HCWs perceived improving AU as a priority, they did not perceive AU or AMR as a problem in their HCF. AS opportunities include improved access to guidelines, access to AMR/AU data, teamwork, and education on AS for HCWs and patients and families.

Deep Dive Into Gaps and Barriers to Implementation of Antimicrobial Stewardship Programs in Hospitals in Latin America.

BACKGROUND: Antimicrobial resistance has worsened in Latin America. There is an urgent need to understand the development of antimicrobial stewardship programs (ASPs) and the barriers to implementing effective ASPs in light of limited national action plans or policies to promote ASPs in the region. METHODS: We performed a descriptive mixed-methods study of ASPs in 5 Latin American countries in March-July 2022. An electronic questionnaire with an associated scoring system (hospital ASP self-assessment) was used, and ASP development was classified based on the scores (inadequate, 0-25; basic, 26-50; intermediate, 51-75; or advanced, 76-100). Interviews among healthcare workers (HCWs) involved in antimicrobial stewardship (AS) inquired about behavioral and organizational factors that influence AS activities. Interview data were coded into themes. Results from the ASP self-assessment and interviews were integrated to create an explanatory framework. RESULTS: Twenty hospitals completed the self-assessment, and 46 AS stakeholders from these hospitals were interviewed. ASP development was inadequate/basic in 35% of hospitals, intermediate in 50%, and advanced in 15%. For-profit hospitals had higher scores than not-for-profit hospitals. Interview data validated the self-assessment findings and provided further insight into ASP implementation challenges, which included limited formal hospital leadership support, inadequate staffing and tools to perform AS work more efficiently, limited awareness of AS principles by HCWs, and limited training opportunities. CONCLUSIONS: We identified several barriers to ASP development in Latin America, suggesting the need to create accurate business cases for ASPs to obtain the necessary funding for their effective implementation and sustainability.

COVID-19 policies in practice and their direct and indirect impacts in Northern California jails

BackgroundAlthough the increased risk of COVID-19 in carceral facilities is well documented, little is known about the practical barriers to infection control and indirect impacts of pandemic policies in these settings. Evidence in jails is especially scarce. MethodsBetween July 8, 2020 and April 30, 2021 we performed SARS-CoV-2 serology testing and administered a questionnaire among residents and staff in four Northern California jails. We analyzed seroprevalence in conjunction with demographic factors and survey responses of self-perceived COVID-19 risk, recent illness, COVID-19 test results, and symptom reporting behaviors. We additionally assessed COVID-19 policies in practice and evaluated their impacts on court dates, mental health, and routine health care. We engaged stakeholder representatives, including incarcerated individuals and their advocates, to guide study design, conduct, and interpretation. ResultsWe enrolled 788 incarcerated individuals and 380 staff across four county jails. Most seropositive individuals had not previously tested positive for COVID-19, despite many suspecting prior infection. Among incarcerated participants, we identified deficient access to face masks and prevalent symptom underreporting associated with fears of isolation and perceptions of medical neglect in jail. Incarcerated participants also reported substantial hindrances to court cases and reductions in routine health care due to COVID-19. Incarcerated individuals and staff both cited worsened mental health due to COVID-19, which for incarcerated individuals was largely attributable to further isolation from loved ones and other pandemic restrictions on recreation and programming. ConclusionPerceptions of inadequate protection from COVID-19 were pervasive among incarcerated individuals. Simultaneously, restrictive measures compounded poor mental health and fostered fears of isolation that undermined effective infection control. Custody officials should work to systematically improve provision of masks, understand and mitigate fears and mistrust, and take proactive steps to minimize the detrimental impacts of restrictive policies on residents mental health and well-being.

Factors associated with COVID-19 vaccine acceptance and hesitancy among residents of Northern California jails

BackgroundCarceral facilities are high-risk settings for COVID-19 transmission. Understanding of factors associated with COVID-19 vaccine acceptance and hesitancy among incarcerated individuals is incomplete, especially for people living in jails. MethodsWe conducted a retrospective review of COVID-19 vaccination data from the electronic health record (EHR) of residents in two Northern California county jails to examine factors associated with vaccine uptake in this population. We additionally administered a survey in four jails to assess reasons for vaccine hesitancy, sources of COVID-19 information, and medical mistrust. We performed multivariate logistic regression to determine associations with vaccine uptake or hesitancy. ResultsOf 2,584 jail residents offered a COVID-19 vaccine between March 19, 2021 and June 30, 2021, 1,464 (56.7%) accepted at least one dose. Among vaccinated residents, 538 (36.7%) initially refused the vaccine. Vaccine uptake was higher among older individuals, women, those with recent flu vaccination, and those living in shared cells or open dorms. Leading reasons for vaccine hesitancy included concerns around side effects and suboptimal efficacy. Television and friends/family were the most commonly cited and the most trusted sources of COVID-19 information, respectively. Vaccine acceptance was associated with increased trust in COVID-19 information sources and in medical personnel both in and out of jail. ConclusionOngoing evidence-based COVID-19 vaccination efforts are needed in high-risk carceral settings. Effective interventions to improve vaccination rates in this population should utilize accessible and trusted sources of information to address concerns about vaccine side effects and efficacy and foster medical trust.

[Overcrowding of emergency services in the city of Bogotá: a systemic understanding of the problem]. / Saturación del servicio de urgencias en la ciudad de Bogotá: una comprensión sistémica del problema.

Emergency overcrowding is often associated with issues of inefficiency in care. However, this work focuses on another relevant aspect, namely care of non-urgent patients. In order to understand the dynamics associated with this aspect, a conceptual model of systems dynamics is constructed, based on the characterization of users and their decision criteria. A descriptive study was conducted based on a structured survey; additionally, binomial logistic regression and analysis of variance were used to estimate probability of emergency department visits and to define differences among users. The following criteria are relevant: service effectiveness, availability of medications and exams, and proximity to the emergency center. The waiting time is more significant for pediatric patients and the availability of medications and exams is also more prevalent for middle-income users; the latter attributes less importance to cost compared to low income. The model shows that resources create a virtuous or a vicious cycle of users waiting for care in both emergency and priority care (PC) centers. The proposal suggested is for segregation for pediatric users in PC centers and the promotion of user confidence in alternative options to emergency centers.

La saturación de urgencias a menudo se asocia con ineficiencias en la atención. Sin embargo, este trabajo centra la mirada en otro aspecto relevante como es la asistencia de usuarios no urgentes. Para comprender las dinámicas asociadas a ello, se construye un modelo conceptual de dinámica de sistemas a partir de una caracterización de usuarios y de sus criterios de decisión. Se realizó un estudio descriptivo a partir de una encuesta estructurada, definiendo, a partir de una regresión logística binomial y un análisis de varianza, las diferencias entre usuarios y su probabilidad de asistencia a urgencias. Se encontraron como criterios relevantes: eficacia del servicio, disponibilidad de medicamentos y exámenes y cercanía del centro a la vivienda. El tiempo de espera es más significativo para pacientes pediátricos y la disponibilidad de medicamentos y exámenes lo es para usuarios de ingreso medio; estos últimos le dan menos importancia al costo comparados con los de ingreso bajo. El modelo muestra que los recursos generan un ciclo virtuoso o vicioso de usuarios en espera de atención tanto en urgencias como en atención prioritaria (AP). Se propone una segregación para usuarios pediátricos en la AP y fomentar la confianza de los usuarios en las opciones alternativas a los centros de urgencias.

Management of Hypersensitivity Reactions to Nondextran Iron Products: New Insights Into Predisposing Risk Factors.

BACKGROUND: Hypersensitivity reactions (HSRs) to nondextran iron products (NDIPs) are rare, but can manifest with severe signs and symptoms. Predisposing risk factors are not well understood. OBJECTIVE: To characterize patients with HSRs to NDIPs, with a special focus on possible risk factors. METHODS: We analyzed clinical characteristics of patients with HSRs to NDIPs referred to our allergy division between 2007 and 2019 compared with tolerant controls, including the type of the eliciting NDIP, severity and characteristics of the HSR, atopy status, history of allergies and urticaria, laboratory and skin test results, and outcome of reexposure with NDIPs. RESULTS: We evaluated the data of 59 patients and 21 controls. Sixteen patients and 4 controls received the NDIP iron sucrose and 41 patients and 15 controls received ferric carboxymaltose. In 2 patients and in 2 controls, the culprit NDIP was not known. Twenty-seven patients (46%) experienced an anaphylactic reaction grade I, 15 (25%) a grade II reaction, and 17 (29%) a grade III reaction according to Ring and Messmer. On analyzing the history, we found that 22 patients (37%) and 3 controls (14%) reported previous HSRs to other medications. Interestingly, more than half the patients (n = 35 [59%]) compared with only 7 controls (33%) reported an episode of any type of urticaria in their previous history. Most patients (n = 15 [79%]) tolerated reexposure of an NDIP using a low-reactogenic administration protocol. CONCLUSIONS: A history of drug hypersensitivity and urticaria represent potential risk factors for HSRs to NDIPs. On the basis of our findings, we propose an algorithm for practical management of patients receiving NDIPs aiming to prevent HSRs.

Knowledge and compliance as factors associated with needlestick injuries contaminated with biological material: Brazil and Colombia. / Conhecimento e adesão como fatores associados a acidentes com agulhas contaminadas com material biológico: Brasil e Colômbia.

This was a cross-sectional study to start a cohort in two University Hospitals of two countries - Brazil and Colombia - for assessing the prevalence of needlestick and sharps injuries (NSI), the level of compliance with standard precautions (SPs), and knowledge on blood borne pathogens and associated factors among health students and professionals, within the framework of the implementation of the NR-32 standard. We created compliance scales based on 12 and 10 questions, for assessing knowledge. We used the Multinomial Poisson-Tweedie Regression to evaluate the relationship between knowledge and compliance with SPs within NSI. We evaluated 965 individuals (348 students and 614 professionals). The mean score points for level of knowledge was 10.98, with a median of 11 (10; 12) and α-Cr of 0,625. Compliance with SP had a mean of 30.74 and median of 31 (28; 34), with a α-Cr coefficient of 0.745, associated with country, group (student) and risk perception. Among the factors associated with the report of NSI, we singled out knowledge and compliance, country of origin, and full vaccination scheme against the Hepatitis B virus. We concluded that the level of knowledge and compliance were adequate among participants, but better among Brazilian participants, and it was associated with NSI reporting.

Fizemos estudo transversal para iniciar coorte em dois Hospitais Universitários de dois países - Brasil e Colômbia - para avaliar a prevalência de acidentes com material biológico (AT-MB), o nível de adesão às Precauções Padrão (PP) e o conhecimento sobre patógenos transmissíveis pelo sangue e fatores associados entre trabalhadores e estudantes da saúde, no marco da implementação da norma NR-32. Criamos escalas para estimar conhecimento e adesão baseadas em 12 e 11 perguntas respectivamente. Utilizamos Regressão de Poisson-Tweedie para avaliar a associação do conhecimento e da adesão às PP com sofrer AT-MB. Avaliamos 965 indivíduos (348 estudantes e 617 profissionais). O conhecimento teve média de 10,98 com mediana de 11 (10, 12) e α-Cr de 0,625. A média de adesão foi de 30,74 com mediana de 31 (28, 34) e α-Cr de 0,745, associando-se a País, grupo (estudantes) e percepção de risco. Entre os fatores associadas ao relato de AT-MB encontraram-se o conhecimento, a adesão às PP, País de origem e ter tomado o esquema completo de vacinação contra Hepatites B. Concluímos que o nível de conhecimento e adesão foram adequados, ainda melhores entre os participantes do Brasil e associaram-se ao relato AT-MB.

Hicimos estudio transversal como punto de partida de estudio de cohorte en dos Hospitales Universitarios en dos países - Brasil y Colombia - para evaluar la prevalencia de accidentes con material biológico (AT-MB), el nivel de adhesión a las Precauciones Estándares (PUs) y el conocimiento sobre patógenos transmisibles y factores asociados entre trabajadores y estudiantes de la Salud en el marco de la implementación de la norma NR-32. Creamos escalas para evaluar el conocimiento y la adhesión con base en 12 e 11 preguntas respectivamente. Utilizamos Regresión de Poisson-Tweedie para evaluar asociación entre el conocimiento y la adhesión a las PUs con sufrir AT-MB. Evaluamos 965 individuos (348 estudiantes e 617 profesionales). El puntaje medio de conocimiento fue 10,98 con mediana de 11 (10, 12) y α-Cr de 0,625. La media de adhesión fue de 30,74 con mediana de 31 (28, 34) e α-Cr de 0,745, asociándose a país, grupo (estudiantes) e percepción de riesgo. Entre los factores asociados al relato de AT-MB encontramos conocimiento, adhesión a las PUs, país de origen y tener el esquema completo de vacunación contra Virus da Hepatitis B. Concluimos que el nivel de conocimiento y adhesión fueron adecuados, aunque mejores entre los participantes del Brasil y se asociaron a los AT-MB.

Conhecimento e adesão como fatores associados a acidentes com agulhas contaminadas com material biológico: Brasil e Colômbia / Knowledge and compliance as factors associated with needlestick injuries contaminated with biological material: Brazil and Colombia / Conocimiento y adhesión como factores asociados a los accidentes con agujas contaminadas con material biológico: Brasil y Colombia

Resumo Fizemos estudo transversal para iniciar coorte em dois Hospitais Universitários de dois países - Brasil e Colômbia - para avaliar a prevalência de acidentes com material biológico (AT-MB), o nível de adesão às Precauções Padrão (PP) e o conhecimento sobre patógenos transmissíveis pelo sangue e fatores associados entre trabalhadores e estudantes da saúde, no marco da implementação da norma NR-32. Criamos escalas para estimar conhecimento e adesão baseadas em 12 e 11 perguntas respectivamente. Utilizamos Regressão de Poisson-Tweedie para avaliar a associação do conhecimento e da adesão às PP com sofrer AT-MB. Avaliamos 965 indivíduos (348 estudantes e 617 profissionais). O conhecimento teve média de 10,98 com mediana de 11 (10, 12) e α-Cr de 0,625. A média de adesão foi de 30,74 com mediana de 31 (28, 34) e α-Cr de 0,745, associando-se a País, grupo (estudantes) e percepção de risco. Entre os fatores associadas ao relato de AT-MB encontraram-se o conhecimento, a adesão às PP, País de origem e ter tomado o esquema completo de vacinação contra Hepatites B. Concluímos que o nível de conhecimento e adesão foram adequados, ainda melhores entre os participantes do Brasil e associaram-se ao relato AT-MB.

Abstract This was a cross-sectional study to start a cohort in two University Hospitals of two countries - Brazil and Colombia - for assessing the prevalence of needlestick and sharps injuries (NSI), the level of compliance with standard precautions (SPs), and knowledge on blood borne pathogens and associated factors among health students and professionals, within the framework of the implementation of the NR-32 standard. We created compliance scales based on 12 and 10 questions, for assessing knowledge. We used the Multinomial Poisson-Tweedie Regression to evaluate the relationship between knowledge and compliance with SPs within NSI. We evaluated 965 individuals (348 students and 614 professionals). The mean score points for level of knowledge was 10.98, with a median of 11 (10; 12) and α-Cr of 0,625. Compliance with SP had a mean of 30.74 and median of 31 (28; 34), with a α-Cr coefficient of 0.745, associated with country, group (student) and risk perception. Among the factors associated with the report of NSI, we singled out knowledge and compliance, country of origin, and full vaccination scheme against the Hepatitis B virus. We concluded that the level of knowledge and compliance were adequate among participants, but better among Brazilian participants, and it was associated with NSI reporting.

Resumen Hicimos estudio transversal como punto de partida de estudio de cohorte en dos Hospitales Universitarios en dos países - Brasil y Colombia - para evaluar la prevalencia de accidentes con material biológico (AT-MB), el nivel de adhesión a las Precauciones Estándares (PUs) y el conocimiento sobre patógenos transmisibles y factores asociados entre trabajadores y estudiantes de la Salud en el marco de la implementación de la norma NR-32. Creamos escalas para evaluar el conocimiento y la adhesión con base en 12 e 11 preguntas respectivamente. Utilizamos Regresión de Poisson-Tweedie para evaluar asociación entre el conocimiento y la adhesión a las PUs con sufrir AT-MB. Evaluamos 965 individuos (348 estudiantes e 617 profesionales). El puntaje medio de conocimiento fue 10,98 con mediana de 11 (10, 12) y α-Cr de 0,625. La media de adhesión fue de 30,74 con mediana de 31 (28, 34) e α-Cr de 0,745, asociándose a país, grupo (estudiantes) e percepción de riesgo. Entre los factores asociados al relato de AT-MB encontramos conocimiento, adhesión a las PUs, país de origen y tener el esquema completo de vacunación contra Virus da Hepatitis B. Concluimos que el nivel de conocimiento y adhesión fueron adecuados, aunque mejores entre los participantes del Brasil y se asociaron a los AT-MB.

Ibrutinib inhibition of ERBB4 reduces cell growth in a WNT5A-dependent manner.

Alterations in ERBB family members have been associated with many tumor malignancies. EGFR and ERBB2 have been extensively explored in clinical oncology and several drugs currently target them therapeutically. However, the significance of ERBB4 as a potential therapeutic target remains mostly unexplored, even though ERBB4 is overexpressed or mutated in many solid tumors. Using a unique functional protein microarray platform, we found that ibrutinib inhibits ERBB4 activity in the same nM range as its canonical target, BTK. Cell-based assays revealed that ibrutinib treatment inhibited cell growth and decreased phosphorylation of ERBB4 and downstream targets MEK and ERK in cancer cell lines with high levels of endogenous ERBB4. In vivo, ibrutinib-responsive mouse xenograft tumors showed decreased tumor volumes with ibrutinib treatment. Interestingly, global gene expression comparisons between responsive and non-responsive cells identified a signature featuring the WNT pathway that predicts growth responsiveness to ibrutinib. Non-responsive ERBB4-expressing cell lines featured elevated activity of the WNT pathway, through the overexpression of WNT5A. Moreover, inhibition of WNT5A expression led to an ibrutinib response in non-responsive cell lines. Our data show that inhibiting ERBB4 reduces cell growth in cells that have low WNT5A expression and reveal a link between the ERBB4 and WNT pathways.

Association Between Left Atrial Compression And Atrial Fibrillation: A Case Presentation And A Short Review Of Literature.

This case report describes a patient who developed palpitations and chest pain and was found to be in atrial fibrillation, which was likely due to the presence of an extra-cardiac mass. This was compressing the left atrium. The mass was related to small cell carcinoma, which decreased significantly in size after chemotherapy. Resolution of the atrial fibrillation correlated temporally with reduction in the size of the mass and alleviation of the left atrial compression.

Assembly Dynamics and Stoichiometry of the Apoptosis Signal-regulating Kinase (ASK) Signalosome in Response to Electrophile Stress.

Apoptosis signal-regulating kinase 1 (ASK1) is a key sensor kinase in the mitogen-activated protein kinase pathway that transduces cellular responses to oxidants and electrophiles. ASK1 is regulated by a large, dynamic multiprotein signalosome complex, potentially including over 90 reported ASK1-interacting proteins. We employed both shotgun and targeted mass spectrometry assays to catalogue the ASK1 protein-protein interactions in HEK-293 cells treated with the prototypical lipid electrophile 4-hydroxy-2-nonenal (HNE). Using both epitope-tagged overexpression and endogenous expression cell systems, we verified most of the previously reported ASK1 protein-protein interactions and identified 14 proteins that exhibited dynamic shifts in association with ASK1 in response to HNE stress. We used precise stable isotope dilution assays to quantify protein stoichiometry in the ASK signalosome complex and identified ASK2 at a 1:1 stoichiometric ratio with ASK1 and 14-3-3 proteins (YWHAQ, YWHAB, YWHAH, and YWHAE) collectively at a 0.5:1 ratio with ASK1 as the main components. Several other proteins, including ASK3, PARK7, PRDX1, and USP9X were detected with stoichiometries of 0.1:1 or less. These data support an ASK signalosome comprising a multimeric core complex of ASK1, ASK2, and 14-3-3 proteins, which dynamically engages other binding partners needed to mediate diverse stress-response signaling events. This study further demonstrates the value of combining global and targeted MS approaches to interrogate multiprotein complex composition and dynamics.

Cystic meningioma simulating arachnoid cyst: report of an unusual case.

The purpose of this paper is to show an unusual case of meningioma simulating arachnoid cyst on CT scan and MRI, diagnosed in a 63-year-old woman evaluated for headache and vision disorders. The meningioma shown is predominantly cystic with a small mural nodule enhancing after gadolinium and exhibiting diffusion restriction. Cystic portion of the tumor is hypodense on CT, and evidences fluid signal intensity on T1- and T2-weighted MR imaging.

Facile labeling of lipoglycans with quantum dots.

Bacterial endotoxins or lipopolysaccharides (LPS) are among the most potent activators of the innate immune system, yet mechanisms of their action and in particular the role of glycans remain elusive. Efficient non-invasive labeling strategies are necessary for studying interactions of LPS glycans with biological systems. Here we report a new method for labeling LPS and other lipoglycans with luminescent quantum dots. The labeling is achieved by partitioning of hydrophobic quantum dots into the core of various LPS aggregates without disturbing the native LPS structure. The biofunctionality of the LPS-Qdot conjugates is demonstrated by the labeling of mouse monocytes. This simple method should find broad applicability in studies concerned with visualization of LPS biodistribution and identification of LPS binding agents.