Membrane Lipids Augment Cell Envelope Stress Signaling via the MadRS System to Defend Against Antimicrobial Peptides and Antibiotics in Enterococcus faecalis.

Enterococci have evolved resistance mechanisms to protect their cell envelopes against bacteriocins and host cationic antimicrobial peptides (CAMPs) produced in the gastrointestinal environment. Activation of the membrane stress response has also been tied to resistance to the lipopeptide antibiotic daptomycin. However, the actual effectors mediating resistance have not been elucidated. Here, we show that the MadRS (formerly YxdJK) membrane antimicrobial peptide defense system controls a network of genes, including a previously uncharacterized three gene operon (madEFG) that protects the E. faecalis cell envelope from antimicrobial peptides. Constitutive activation of the system confers protection against CAMPs and daptomycin in the absence of a functional LiaFSR system and leads to persistence of cardiac microlesions in vivo. Moreover, changes in the lipid cell membrane environment alter CAMP susceptibility and expression of the MadRS system. Thus, we provide a framework supporting a multilayered envelope defense mechanism for resistance and survival coupled to virulence.

Soledad, ansiedad, depresión y adopción del rol del cuidador de personas con enfermedad crónica en San Gil, Colombia

Introducción: Los cuidadores de personas con enfermedad crónica adoptan un nuevo rol que puede implicar respuestas como ansiedad, depresión y soledad. Objetivo: Describir y correlacionar las variables de adopción del rol del cuidador, depresión, ansiedad y soledad en cuidadores familiares de personas con enfermedad crónica en la provincia de Guanentina, en San Gil, Santander (Colombia), durante el año 2021. Método: Estudio descriptivo, analítico de corte transversal realizado con 112 cuidadores familiares de personas con enfermedades crónicas. Se utilizó una ficha de caracterización y los instrumentos: Escala adopción del rol del cuidador ROL, escala de soledad de UCLA (University of California at Los Ángeles) y Escala Hospitalaria de Ansiedad y Depresión HADS. Resultados: El perfil de los cuidadores fue predominantemente mujer; de 49 años en promedio; casadas, solteras o en unión libre; grado máximo de escolaridad bachiller; de ocupación hogar y nivel socioeconómico medio bajo y bajo. Se encontraron niveles altos de ansiedad en el 18,3 % de ellas, depresión en el 4,3 % y soledad en el 0,9 %, además, se evidenciaron niveles de adopción del rol del cuidador satisfactorios en el 100 %. Se encontró una correlación débil entre ansiedad, depresión y soledad y una correlación inversa entre estas variables con la adopción del rol del cuidador. De igual manera, se encontró una correlación directa entre la edad del paciente y los meses de diagnóstico con las horas de cuidado al día. Por último, se halló carácter predictivo de la ansiedad y la depresión sobre la adopción del rol, de la ansiedad y la adopción del rol sobre la depresión, y de la soledad y la depresión sobre la ansiedad. Conclusiones: los cuidadores tenían niveles de ansiedad, depresión y soledad normales que, al correlacionarse entre sí y con la adopción del rol del cuidador, validan la idea de que, si se interviene a los cuidadores en su trayectoria con orientaciones sobre su rol en cuanto a las labores, la organización y las respuestas se puede contribuir en la disminución de la ansiedad, depresión y soledad. Discusión: la correlación directa observada entre la soledad, depresión y ansiedad es coherente con lo reportado en estudios previos con cuidadores. Acorde con lo reportado por la literatura el desempeño satisfactorio del rol facilita los desenlaces en los cuidadores, en este caso, la moderación de la ansiedad, depresión y soledad.

Introduction: Caregivers of people with chronic disease adopt a new role that may involve responses such as anxiety, depression, and loneliness. Objective: To describe and correlate the variables of adoption of the role of caregiver, depression, anxiety and loneliness in family caregivers of people with chronic disease in the Guanentina province in San Gil, Santander (Colombia), during the year 2021. Methods: Descriptive study, cross-sectional analysis carried out with 112 family caregivers of people with chronic diseases. A characterization sheet and the ROL, UCLA and HADS instruments were used. Results: the profile of the caregivers was predominantly female and average age of 49 years; married, single or in civil union; maximum degree of high school education; of household occupation and low and low-middle socioeconomic level. High levels of anxiety were found in 18,3% of them, depression in 4,3% and loneliness in 0,9%, in addition, satisfactory levels of adoption of the caregiver role were evidenced in 100%. A weak correlation was found between anxiety, depression and loneliness and an inverse correlation between these variables with the adoption of the caregiver role. Similarly, a direct correlation was found between the patient's age and the months of diagnosis with the hours of care per day. Finally, anxiety and depression were found to be predictive of role adoption, of anxiety and role adoption on depression, and of loneliness and depression on anxiety. Conclusions: the caregivers had normal levels of anxiety, depression and loneliness that, when correlated with each other and with the adoption of the caregiver role, validate the idea that, if caregivers are intervened in their trajectory with guidance on their role in terms of the tasks, the organization and the answers can contribute in the reduction of anxiety, depression and loneliness. Discussion: The direct connection observed between loneliness, depression and anxiety is consistent with what has been reported in previous studies with caregivers. In accordance with what has been reported in the literature, satisfactory performance of the role facilitates the outcomes in caregivers, in this case, the moderation of anxiety, depression and loneliness.

Instrumentos para la medición de sobrecarga del cuidador en pacientes con enfermedad crónica: revisión psicométrica

Introducción: Los cuidadores de pacientes con enfermedad crónica experimentan sobrecarga en actividades de cuidado. Existen diferentes instrumentos que miden la sobrecarga, en Latinoamérica se han validado diferentes instrumentos. Objetivo: Evaluar la calidad metodológica de las propiedades psicométricas de los instrumentos que miden la sobrecarga del cuidador en el contexto latinoamericano. Metodología: Revisión sistemática psicométrica. La búsqueda incluyó la combinación de 3 aspectos: estudios de validación; idioma: español, portugués o inglés, lugar de validación: Latinoamérica. Resultados: Un total de 24 artículos se identificaron e incluían 10 instrumentos. El idioma de los artículos con mayor representación fue el español (n = 15). El país con mayor número de estudios de validación fue Brasil (n = 15). El instrumento con mayor número de validaciones fue la Encuesta de Zarit (n = 11). Conclusión: Los instrumentos identificados cuentan con buena calidad metodológica, sin embargo, se requieren futuros estudios que evalúen las propiedades psicométricas faltantes, en especial la validez de contenido.

Introduction: Caregivers of patients with chronic disease experience overload when carrying out continuous care tasks. In the world there are different instruments that measure this overload, in the Latin American context different instruments have been validated. Objetive: To evaluate the methodological quality of the psychometric properties of the instruments that measure caregiver burden in the Latin American. Methodology: Systematic psychometric review. The search included the combination of 3 aspects: validation studies; language: Spanish, Portuguese or English, and place of validation: Latin American. Results: A total of 24 articles were identified and included 10 instruments. The language of the articles with the highest representation was Spanish (n = 15). The country with the highest number of validation studies was Brazil (n = 15). The instrument with the highest number of validations was the Zarit Survey (n = 11). Conclusion: The identified instruments have methodological quality; however, future research is necessary to evaluate the missing psychometric properties, especially content validity

Membrane Lipids Augment Cell Envelope Stress Signaling and Resistance to Antibiotics and Antimicrobial Peptides in Enterococcus faecalis.

Enterococci have evolved resistance mechanisms to protect their cell envelopes against bacteriocins and host cationic antimicrobial peptides (CAMPs) produced in the gastrointestinal environment. Activation of the membrane stress response has also been tied to resistance to the lipopeptide antibiotic daptomycin. However, the actual effectors mediating resistance have not been elucidated. Here, we show that the MadRS (formerly YxdJK) membrane antimicrobial peptide defense system controls a network of genes, including a previously uncharacterized three gene operon (madEFG) that protects the E. faecalis cell envelope from antimicrobial peptides. Constitutive activation of the system confers protection against CAMPs and daptomycin in the absence of a functional LiaFSR system and leads to persistence of cardiac microlesions in vivo. Moreover, changes in the lipid cell membrane environment alter CAMP susceptibility and expression of the MadRS system. Thus, we provide a framework supporting a multilayered envelope defense mechanism for resistance and survival coupled to virulence.

Modified Early Warning Score: Clinical Deterioration of Mexican Patients Hospitalized with COVID-19 and Chronic Disease.

The objective was to evaluate the Modified Early Warning Score in patients hospitalized for COVID-19 plus chronic disease. METHODS: Retrospective observational study, 430 hospitalized patients with COVID-19 and chronic disease. Instrument, Modified Early Warning Score (MEWS). Data analysis, with Cox and logistic regression, to predict survival and risk. RESULTS: Of 430 patients, 58.6% survived, and 41.4% did not. The risk was: low 53.5%, medium 23.7%, and high 22.8%. The MEWS score was similar between survivors 3.02, p 0.373 (95% CI: -0.225-0.597) and non-survivors 3.20 (95% CI: -0.224-0.597). There is a linear relationship between MEWS and mortality risk R 0.920, ANOVA 0.000, constant 4.713, and coefficient 4.406. The Cox Regression p 0.011, with a risk of deterioration of 0.325, with a positive coefficient, the higher the risk, the higher the mortality, while the invasive mechanical ventilation coefficient was negative -0.757. By providing oxygen and ventilation, mortality is lower. CONCLUSIONS: The predictive value of the modified early warning score in patients hospitalized for COVID-19 and chronic disease is not predictive with the MEWS scale. Additional assessment is required to prevent complications, especially when patients are assessed as low-risk.

Case management as an opportunity for healthcare: user experiences

Introduction: People with multimorbidity and their caregivers are beginning to be recognized as emerging subjects of health systems. In Colombia there is no differentiated approach to care for this population, as well as its health-disease process. Objective: To understand the experience of people with multimorbidity and their caregivers after receiving a case management intervention. Methods and materials: It is a qualitative study in which 33 participants among people with multimorbidity and their caregivers who received intervention with case managers were interviewed, a comparative analysis and use to tools analytics grounded theory. Results: There are 3 dimensions that are, the actors where nursing becomes relevant as a reliable source of care; the Care Meeting, as a space created within case management to maintain trust and; Results in the health system, where the need to integrate this type of outbreak into the Colombian Health Model is confirmed. Discussion: Complementary qualitative evidence data from the central study with a greater impact on the quality of care through the therapeutic relationship at home. Conclusion: The dyad requires home support for self-management of the disease based on trust, empathy, empowerment and administrative management carried out by case managers.

Introducción: Las personas con multimorbilidad y sus cuidadores empiezan a ser reconocidos como sujetos emergentes en los sistemas de salud. En Colombia no existe un abordaje diferenciado para la atención de esta población, así como de su proceso de salud-enfermedad. Objetivo: Entender las experiencias de personas con multimorbilidad y sus cuidadores tras recibir una intervención de gestión de casos. Materiales y métodos: Estudio cualitativo en el que se entrevistó a 33 participantes con multimorbilidad y sus cuidadores que recibieron una intervención por parte de gestores de casos; se realizó un análisis comparativo y se utilizaron herramientas analíticas de la teoría fundamentada. Resultados: Existen tres dimensiones: los actores, donde la enfermería cobra relevancia como fuente confiable de cuidado; la reunión de atención o cuidado, como un espacio creado en la gestión de casos para mantener la confianza; y resultados en el sistema de salud, donde se confirma la necesidad de integrar este tipo de avance en el modelo de salud colombiano. Discusión: Los datos cualitativos complementarios del estudio central evidencian un mayor impacto en la calidad del cuidado a través de la relación terapéutica en el hogar. Conclusión: La díada requiere acompañamiento domiciliario para la autogestión de la enfermedad que esté basado en la confianza, la empatía, el empoderamiento y la gestión administrativa llevada a cabo por los gestores de casos.

Introdução: As pessoas com multimorbidade e seus cuidadores estão começando a ser reconhecidos como sujeitos emergentes dos sistemas de saúde. Na Colômbia, não há uma abordagem diferenciada para o atendimento dessa população, bem como para seu processo saúde-doença. Objetivo: Compreender a experiência de pessoas com multimorbidade e seus cuidadores após receberem uma intervenção de gerenciamento de casos. Métodos e materiais: Trata-se de um estudo qualitativo no qual foram entrevistados 33 participantes entre pessoas com multimorbidade e seus cuidadores que receberam intervenção com gerentes de caso, uma análise comparativa e o uso de ferramentas analíticas da teoria fundamentada. Resultados: Existem três dimensões que são: os atores onde a enfermagem se torna relevante como uma fonte confiável de cuidados; a Reunião de Cuidados, como um espaço criado dentro do gerenciamento de casos para manter a confiança e; Resultados no sistema de saúde, onde a necessidade de integrar esse tipo de surto no modelo de saúde colombiano é confirmada. Discussão: Dados complementares de evidências qualitativas do estudo central com maior impacto na qualidade do atendimento por meio da relação terapêutica no domicílio. Conclusão: A díade requer apoio domiciliar para o autogerenciamento da doença com base na confiança, empatia, empoderamento e gerenciamento administrativo realizado pelos gerentes de caso.

Heavy Metal Pollution From a Major Earthquake and Tsunami in Chile Is Associated With Geographic Divergence of Clinical Isolates of Methicillin-Resistant Staphylococcus aureus in Latin America.

Methicillin-resistant Staphylococcus aureus (MRSA) is a priority pathogen listed by the World Health Organization. The global spread of MRSA is characterized by successive waves of epidemic clones that predominate in specific geographical regions. The acquisition of genes encoding resistance to heavy-metals is thought to be a key feature in the divergence and geographical spread of MRSA. Increasing evidence suggests that extreme natural events, such as earthquakes and tsunamis, could release heavy-metals into the environment. However, the impact of environmental exposition to heavy-metals on the divergence and spread of MRSA clones has been insufficiently explored. We assess the association between a major earthquake and tsunami in an industrialized port in southern Chile and MRSA clone divergence in Latin America. We performed a phylogenomic reconstruction of 113 MRSA clinical isolates from seven Latin American healthcare centers, including 25 isolates collected in a geographic area affected by an earthquake and tsunami that led to high levels of heavy-metal environmental contamination. We found a divergence event strongly associated with the presence of a plasmid harboring heavy-metal resistance genes in the isolates obtained in the area where the earthquake and tsunami occurred. Moreover, clinical isolates carrying this plasmid showed increased tolerance to mercury, arsenic, and cadmium. We also observed a physiological burden in the plasmid-carrying isolates in absence of heavy-metals. Our results are the first evidence that suggests that heavy-metal contamination, in the aftermath of an environmental disaster, appears to be a key evolutionary event for the spread and dissemination of MRSA in Latin America.

Dynamics of the MRSA Population in a Chilean Hospital: a Phylogenomic Analysis (2000-2016).

The global dissemination of methicillin-resistant Staphylococcus aureus (MRSA) is associated with the emergence and establishment of clones in specific geographic areas. The Chilean-Cordobes clone (ChC) (ST5-SCCmecI) has been the predominant MRSA clone in Chile since its first description in 1998, despite the report of other emerging MRSA clones in recent years. Here, we characterize the evolutionary history of MRSA from 2000 to 2016 in a Chilean tertiary health care center using phylogenomic analyses. We sequenced 469 MRSA isolates collected between 2000 and 2016. We evaluated the temporal trends of the circulating clones and performed a phylogenomic reconstruction to characterize the clonal dynamics. We found a significant increase in the diversity and richness of sequence types (STs; Spearman r = 0.8748, P < 0.0001) with a Shannon diversity index increasing from 0.221 in the year 2000 to 1.33 in 2016, and an effective diversity (Hill number; q = 2) increasing from 1.12 to 2.71. The temporal trend analysis revealed that in the period 2000 to 2003 most of the isolates (94.2%; n = 98) belonged to the ChC clone. However, since then, the frequency of the ChC clone has decreased over time, accounting for 52% of the collection in the 2013 to 2016 period. This decline was accompanied by the rise of two emerging MRSA lineages, ST105-SCCmecII and ST72-SCCmecVI. In conclusion, the ChC clone remains the most frequent MRSA lineage, but this lineage is gradually being replaced by several emerging clones, the most important of which is clone ST105-SCCmecII. To the best of our knowledge, this is the largest study of MRSA clonal dynamics performed in South America. IMPORTANCE Methicillin-resistant Staphylococcus aureus (MRSA) is a major public health pathogen that disseminates through the emergence of successful dominant clones in specific geographic regions. Knowledge of the dissemination and molecular epidemiology of MRSA in Latin America is scarce and is largely based on small studies or more limited typing techniques that lack the resolution to represent an accurate description of the genomic landscape. We used whole-genome sequencing to study 469 MRSA isolates collected between 2000 and 2016 in Chile providing the largest and most detailed study of clonal dynamics of MRSA in South America to date. We found a significant increase in the diversity of MRSA clones circulating over the 17-year study period. Additionally, we describe the emergence of two novel clones (ST105-SCCmecII and ST72-SCCmecVI), which have been gradually increasing in frequency over time. Our results drastically improve our understanding of the dissemination and update our knowledge about MRSA in Latin America.

Sobrecarga del cuidador familiar en Colombia: revisión sistemática exploratoria / Family caregiver's overburden in Colombia: An exploratory systematic review / Sobrecarga do cuidador familiar na Colômbia: revisão sistemática exploratória

Objetivo:describir las tendencias metodológicas, las poblaciones estudiadas y los desafíos futuros reportados en la literatura sobre lasobrecarga delcuidador familiar colombiano.Métodos:revisión sistemática exploratoria en donde se consultaron las bases de datos PubMed, ScienceDirect, Lilacs, Cuiden, SciELO, EBSCO y BVS, específicamente artículos originalespublicados del 2016 al 2021. Resultados:en 20 artículos revisados, se encontró una relación directa entre condiciones socioeconómicas y la sobrecarga del cuidador. El contexto cultural y las condiciones socioeconómicas son factores que influyen en la percepción de la sobrecarga del cuidador. Conclusiones:son necesarias las intervenciones de enfermeríadirigidasa los cuidadores familiares para mejorar su percepción de la sobrecarga y consecuentemente la calidad de vida

Objective: To describe methodological trends, populations studied, and future challenges reported in the literature on Colombian family caregivers' overburden. Methods: An exploratory systematic review using PubMed, ScienceDirect, LILACS, Cuiden, SciELO, EBSCO, and VHL databases was conducted, specifically original articles published between 2016 and 2021 were reviewed. Results:In 20 articles reviewed, a direct relationship was found between socioeconomic conditions and caregiver's overburden. Cultural context and socioeconomic conditions are factors that influence the perception of caregiver's overburden. Conclusions:Nursing interventions aimed at family caregivers are needed to improve their perception of overburden and, consequently, their quality of life

Objetivo:Descrever as tendências metodológicas, as populações estudadas e os desafios futuros relatados na literatura desobrecarga do cuidador familiar colombiano. Métodos:Revisão sistemática exploratória na qual foram consultadas as bases de dados PubMed, ScienceDirect, Lilacs, Cuiden, SciELO, EBSCO e BVS, com artigos originais, publicados de 2016 a 2021. Resultados:Em 20 artigos revisados, foi encontrada uma relação direta entre condições socioeconômicas e a sobrecarga do cuidador. O contexto cultural e as condições socioeconômicas são fatores que influenciam na percepção da sobrecarga do cuidador. Conclusões:As intervenções de enfermagem voltadas a cuidadores familiares são necessárias para melhorar sua percepção de sobrecarga e, consequentemente, sua qualidade de vida.

A Theoretical Analysis of Interaction Energies and Intermolecular Interactions between Amphotericin B and Potential Bioconjugates Used in the Modification of Nanocarriers for Drug Delivery.

Amphotericin B (AmB) is an antibiotic with a wide spectrum of action and low multidrug resistance, although it exhibits self-aggregation, low specificity, and solubility in aqueous media. An alternative for its oral administration is its encapsulation in polymers modified with bioconjugates. The aim of the present computational research is to determine the affinity between AmB and six bioconjugates to define which one could be more suitable. The CAM-B3LYP-D3/6-31+G(d,p) method was used for all computational calculations. The dimerization enthalpy of the most stable and abundant systems at pH = 7 allows obtaining this affinity order: AmB_1,2-distearoyl-sn-glycerol-3-phosphorylethanolamine (DSPE) > AmB_γ-cyclodextrin > AmB_DSPEc > AmB_retinol > AmB_cholesterol > AmB_dodecanol, where DSPEc is a DSPE analog. Quantum theory of atoms in molecules, the non-covalent interactions index, and natural bond orbital analysis revealed the highest abundance of noncovalent interactions for AmB-DSPE (51), about twice the number of interactions of the other dimers. Depending on the interactions' strength and abundance of the AmB-DSPE dimer, these are classified as strong: O-H---O (2), N-H---O (3) and weak: C-H---O (25), H---H (18), C-H---C (3). Although the C-H---O hydrogen bond is weak, the number of interactions involved in all dimers cannot be underestimated. Thus, non-covalent interactions drive the stabilization of copolymers, and from our analysis, the most promising candidates for encapsulating are DSPE and γ-cyclodextrin.

Rarecare: A policy perspective on the burden of rare diseases on caregivers in Latin America.

In Latin America (LA), 40-50 million people live with rare diseases (RDs) that require constant monitoring, care, and attention. Caregivers help them with their basic life activities and medication administration, which they would otherwise be unable to perform. Family caregivers complement healthcare and social security systems; however, their unpaid work is often underappreciated and under-protected. Recognizing the need to address these unrecognized and undervalued women, the Americas Health Foundation (AHF) convened a panel of LA experts on caregiving for people with RDs to provide recommendations to support the undervalued family caregivers. A panel of LA experts in caregiving for RDs were given questions to address the challenges faced by family caregivers of people with RDs in LA. During a 3-day conference, the panelists' responses were discussed and edited until the panel agreed on recommendations to address the challenges. The identified challenges for caregivers included physical, emotional, and economical areas. Caregivers, primarily women, experienced physical pain, and social isolation, and were forced to pay substantial out-of-pocket expenses in their caregiving roles. Brazil and Colombia are at the forefront of policies to protect caregivers and their experiences in attempting to provide for this group are outlined as case studies for what is possible in LA. Finally, recognizing that caregivers must be included in formulating, executing, and evaluating care policies for people living with RDs and that the caregivers themselves require social assurances, the panel suggested policy objectives aimed at protecting caregivers of people living with RDs. The recommendations ranged from recognizing the role of the family caregiver as an essential supplement to the formal healthcare system to providing financial assistance, training, and workplace protection, among others. Finally, monitoring and evaluating the impact of policies is necessary to ensure that LA is moving forward in caring for family caregivers for people with RDs.

Lifestyle Modifications and Nutritional and Therapeutic Interventions in Delaying the Progression of Chronic Kidney Disease: A Review.

Chronic kidney disease (CKD) is a debilitating progressive illness that affects more than 10% of the world's population. In this literature review, we discussed the roles of nutritional interventions, lifestyle modifications, hypertension (HTN) and diabetes mellitus (DM) control, and medications in delaying the progression of CKD. Walking, weight loss, low-protein diet (LPD), adherence to the alternate Mediterranean (aMed) diet, and Alternative Healthy Eating Index (AHEI)-2010 slow the progression of CKD. However, smoking and binge alcohol drinking increase the risk of CKD progression. In addition, hyperglycemia, altered lipid metabolism, low-grade inflammation, over-activation of the renin-angiotensin-aldosterone system (RAAS), and overhydration (OH) increase diabetic CKD progression. The Kidney Disease: Improving Global Outcomes (KDIGO) guidelines recommend blood pressure (BP) control of <140/90 mmHg in patients without albuminuria and <130/80 mmHg in patients with albuminuria to prevent CKD progression. Medical therapies aim to target epigenetic alterations, fibrosis, and inflammation. Currently, RAAS blockade, sodium-glucose cotransporter-2 (SGLT2) inhibitors, pentoxifylline, and finerenone are approved for managing CKD. In addition, according to the completed Study of Diabetic Nephropathy with Atrasentan (SONAR), atrasentan, an endothelin receptor antagonist (ERA), decreased the risk of renal events in diabetic CKD patients. However, ongoing trials are studying the role of other agents in slowing the progression of CKD.

Clinical characteristics, microbiology and outcomes of a cohort of patients treated with ceftolozane/tazobactam in acute care inpatient facilities, Houston, Texas, USA.

Background: Ceftolozane/tazobactam is a ß-lactam/ß-lactamase inhibitor combination with activity against a variety of Gram-negative bacteria, including MDR Pseudomonas aeruginosa. This agent is approved for hospital-acquired and ventilator-associated bacterial pneumonia. However, most real-world outcome data come from small observational cohorts. Thus, we sought to evaluate the utilization of ceftolozane/tazobactam at multiple tertiary hospitals in Houston, TX, USA. Methods: We conducted a multicentre retrospective study of patients receiving at least 48 h of ceftolozane/tazobactam therapy from January 2016 through to September 2019 at two hospital systems in Houston. Demographic, clinical and microbiological data were collected, including the infecting bacterial isolate, when available. The primary outcome was composite clinical success at hospital discharge. Secondary outcomes included in-hospital mortality and clinical disposition at 14 and 30 days post ceftolozane/tazobactam initiation. Multivariable logistic regression analysis was used to identify predictors of the primary outcome and mortality. Recovered isolates were tested for susceptibility to ceftolozane/tazobactam and underwent WGS. Results: A total of 263 patients were enrolled, and composite clinical success was achieved in 185 patients (70.3%). Severity of illness was the most consistent predictor of clinical success. Combination therapy with ceftolozane/tazobactam and another Gram-negative-active agent was associated with reduced odds of clinical success (OR 0.32, 95% CI 0.16-0.63). Resistance to ceftolozane/tazobactam was noted in 15.4% of isolates available for WGS; mutations in ampC and ftsI were common but did not cluster with a particular ST. Conclusions: Clinical success rate among this patient cohort treated with ceftolozane/tazobactam was similar compared with previous experiences. Ceftolozane/tazobactam remains an alternative agent for treatment of susceptible isolates of P. aeruginosa.

Relationship between Burden and Perceived Social Support in Low-income Caregivers Authors / Relación entre la sobrecarga y el apoyo social percibido en cuidadores de bajos ingresos económicos / Relação entre sobrecarga e apoio social percebido em cuidadores de baixa renda

Objectives: To describe and correlate burden and social support in low-income caregivers of chronic patients. Material and methods: A descriptive and cross-sectional study was conducted with 170 low-income family caregivers of people with chronic diseases who answered a survey on sociodemographic and care variables, in addition to the Zarit scale to measure burden and the MOS questionnaire on perceived social support. The analysis was performed using descriptive and differential statistics. Results: Most caregivers were female, and the predominant kinship was father-son. A significant and negative correlation (rs = -.307, p < 0.001) was identified between the caregivers' burden and perceived social support, as well as a significant and positive correlation (rs = 0.278, p < 0.01) between the time devoted to care and the caregivers' burden. Conclusions: Low-income family caregivers require more social support to reduce the burden levels.

Objetivos: describir y correlacionar la sobrecarga y el apoyo social de cuidadores de pacientes crónicos con bajos ingresos económicos. Material y métodos: estudio descriptivo transversal realizado a 170 cuidadores familiares de personas con enfermedad crónica de bajos ingresos económicos a quienes se les aplicó una encuesta sobre variables sociodemográficas y de cuidado, además de la escala Zarit para medir la sobrecarga y el cuestionario MOS sobre apoyo social percibido. El análisis se realizó mediante estadística descriptiva y diferencial. Resultados: la mayoría de los cuidadores fueron mujeres y el vínculo filial predominante fue de padre e hijo. Se identificó una correlación significativa y negativa (rs = -0,307, p < 0,001) entre la sobrecarga del cuidador y el apoyo social percibido, como también una correlación significativa y positiva (rs = 0,278, p < 0,001) entre el tiempo dedicado al cuidado y la carga del cuidador. Conclusiones: los cuidadores familiares de bajos ingresos económicos requieren mayor apoyo social para disminuir los niveles de sobrecarga.

Objetivos: Descrever e correlacionar a sobrecarga e o suporte social de cuidadores de baixa renda de pacientes crônicos. Material e métodos: Estudo descritivo e transversal, realizado com 170 cuidadores familiares de baixa renda de pessoas com doenças crônicas, que responderam a um questionário sobre variáveis sociodemográficas e assistenciais, além da escala de Zarit para medir a sobrecarga e do questionário MOS sobre suporte social percebido. A análise foi realizada por meio de estatística descritiva e diferencial. Resultados: A maioria dos cuidadores era do sexo feminino e o vínculo filial predominante era entre pai e filho. Foi identificada uma correlação significativa e negativa (rs = -0,307, p < 0,001) entre a sobrecarga do cuidador e o suporte social percebido, assim como uma correlação significativa e positiva (rs = 0,278, p < 0,001) entre o tempo dedicado ao cuidado e a carga do cuidador. Conclusões: Os cuidadores familiares de baixa renda necessitam de maior suporte social para reduzir os níveis de sobrecarga.

Palliative care and end of life care in Latin America: scoping review

INTRODUCTION: Populational aging and improved treatments for chronic non-communicable diseases extend life expectancy but not always quality of life. By 2060, 48 million people are expected to die of serious illnesses, and 83% of these deaths will occur in developing countries. Only 14% of those who needed palliative care receive it. AIM: To describe the methodological trends, thematic areas, populations studied, and future challenges in Latin American regions with respect to adult palliative care. METHODS: A scoping review of 60 articles from 2010 to 2019 in indexed journals in English, Spanish, and Portuguese was conducted. RESULTS: Most articles were from Brazil, Colombia, and Mexico. Patients, caregivers, healthcare professionals, and students constituted the primary study population. Quality of Life, knowledge, and costs of attention were also assessed. It appears that early palliative care improves the outcomes of patients, caregivers, and health care professionals, however, the disparity in palliative care services between Latin America, US, UK, Canada, and Spain is concerning. CONCLUSIONS: Globally, more palliative care is needed, especially in Latin America. However, there are not enough graduate palliative care programs. Academic palliative care education must be promoted. Communication between the interdisciplinary team, the patient, and the caregiver is critical. While the region's scientific literature output has improved, many knowledge gaps remain. For patients' sake, governments should regulate, create, and facilitate palliative care services.

Temor, estrés, conocimientos, actitudes y prácticas ante la COVID-19 en cuidadores familiares de pacientes crónicos / Fear, stress, knowledge, attitudes and practices in the face of COVID-19 in family caregivers of chronic patients / Temor, estresse, conhecimentos, atitudes e práticas perante a COVID-19 em cuidadores familiares de pacientes crónicos

Resumen La pandemia por COVID-19 ha tenido un impacto sobredimensionado en Colombia en términos de incidencia y mortalidad. Cuidadores familiares de personas con enfermedad crónica asumen el cuidado a largo plazo en el entorno domiciliario en medio del colapso hospitalario. Objetivo: describir, correlacionar e identificar variables predictoras de los conocimientos, actitudes, prácticas, estrés y temor ante la COVID-19 en cuidadores familiares de personas con enfermedad crónica. Metodología: se realizó un estudio trasversal predictivo con 104 cuidadores familiares de personas con enfermedad crónica en Bogotá, Colombia. En el que los instrumentos de caracterización, temor, estrés, conocimientos, actitudes y prácticas ante el COVID-19 fueron aplicados en línea en el segundo semestre de 2020. Resultados: se observó una media de 23.07 (DE=7.2) en temor, 93.18 (DE=31.6) en estrés, 10.1 (DE=1.9) en conocimientos, 1.34 (DE=0.8) en actitudes y 1.89 (DE=0.3), lo que muestra que, aunque los conocimientos, actitudes y prácticas tienen niveles altos, se observan altos niveles de estrés y temor ante el COVID-19. Hay una relación directa entre el temor y estrés ante el COVID-19, con peores puntajes en mujeres y personas con bajo nivel de conocimiento. Conclusión: se requiere capacitación y apoyo sostenido a los cuidadores familiares, quienes, en medio del temor y estrés ante el COVID-19, continúan sosteniendo el cuidado a largo plazo de enfermos crónicos en el entorno domiciliario.

Abstract The COVID-19 pandemic has had an disproportioned impact in Colombia in terms of incidence and mortality. Family caregivers of people with chronic illness take on long-term care in the home setting amid hospital collapse. Objective: To describe, correlate and identify predictor variables of knowledge, attitudes, practices, stress and fear of COVID-19 in family caregivers of people with chronic disease. Methodology: A predictive crosssectional study was conducted with 104 family caregivers of people with chronic disease in Bogotá-Colombia. The instruments of characterization, fear, stress, knowledge, attitudes and practices before COVID-19 were applied online in the second semester of 2020. Results: A mean of 23.07 (SD = 7.2) was observed in fear, 93.18 (SD = 31.6) in stress, 10.1 (SD = 1.9) in knowledge, 1.34 (SD=0.8) in attitudes and 1.89 (SD=0.3) in practices, which shows that, although knowledge, attitudes and practices have high levels, there is a high level of stress and fear of COVID-19. There is a direct relationship between fear and stress in the face of COVID-19, with worse scores in women and people with a low level of knowledge. Conclusion: Training and sustained support is required for family caregivers, who amidst the fear and stress of COVID-19 continue to support the long-term care of chronic patients in the home environment.

Resumo A pandemia pelo COVID-19 tem tido um impacto sobre dimensionado na Colômbia em termos de incidência e mortalidade. Cuidadores familiares de pessoas com doença crónica assumem o cuidado a longo prazo no entorno domiciliário em meio do colapso hospitalário. Objetivo: descrever, correlacionar e identificar variáveis preditoras dos conhecimentos, atitudes, práticas, estresse e temor perante a COVID-19 em cuidadores familiares de pessoas com doença crónica. Metodologia: Realizou-se um estudo transversal preditivo com 104 cuidadores familiares de pessoas com doença crónica em Bogotá, Colômbia. No que os instrumentos de caracterização, temor, estresse, conhecimentos, atitudes e práticas perante a COVID-19 foram aplicados online no segundo semestre de 2020. Resultados: Observou-se uma média de 23.07 (DE=7.2) em temor, 93.18 (DE=31.6) em estresse, 10.1 (DE=1.9) em conhecimentos, 1.34 (DE=0.8) em atitudes e 1.89 (DE=0.3), o que amostra que, porém os conhecimentos, atitudes práticas têm níveis altos, observam-se altos níveis de estresse e temor perante o COVID-19. Há uma relação direta entre o temor e estresse perante a COVID-19, com piores pontuações em mulheres e pessoas com baixo nível de conhecimento. Conclusão: Requer-se capacitação e apoio sustentado aos cuidadores familiares, quem, em meio do temor e estresse perante a COVID-19, continuam sustentando o cuidado a longo prazo de doentes crónicos no entorno domiciliário.

Adopting the Role of Caregiver of Chronic Patients: Specific Situation Theory / Adopción del rol del cuidador del paciente crónico: teoría de situación específica / Adoção do papel do cuidador do paciente crônico: teoria de situação específica

Abstract Objective: To present the proposal for a specific situation theory on adopting the role of caregiver of chronic patients. Materials and methods: Based on Meleis and Im's integrating strategy, multiple information sources were employed to develop this theory. Results: This prescriptive theory derives from Meleis' mid-range theory based on an exhaustive literature review and the authors' practical and research experience. The information was integrated into core concepts such as caregiver's transition, caregiver role insufficiency, nature and conditions of the transition, nursing transitional care for the caregiver, and healthy transition. Assertions were also derived, such as the adoption of the caregiver role influencing the response patterns or the result indicators related to the caregiver's quality of life and perception of burden. Finally, a theoretical process and an empirical indicator called ROLE are described. Conclusions: This theoretical development recognizes the process faced by caregivers in adopting their role in the care of chronic patients and guides possible nursing interventions to favor a healthy transition.

Resumen Objetivo: dar a conocer una propuesta de teoría de situación específica sobre la adopción del rol del cuidador del paciente crónico. Materiales y métodos: basados en la estrategia integradora de Meleis e Im, se emplearon múltiples fuentes de información para el desarrollo de esta teoría. Resultados: esta teoría de carácter prescriptivo se deriva de la teoría de rango medio de las transiciones de Meleis, a partir de una exhaustiva revisión de literatura y de la experiencia práctica e investigativa de las autoras. Se integró la información en conceptos centrales como: transición del cuidador, insuficiencia del rol de cuidador, naturaleza de la transición, condiciones de transición, cuidado transicional de enfermería al cuidador y transición saludable; se derivaron afirmaciones como que la adopción del rol de cuidador influencia los patrones de respuesta o indicadores de resultado relacionados con la calidad de vida y la percepción de sobrecarga del cuidador; se describe un proceso teórico y un indicador empírico denominado ROL. Conclusiones: este desarrollo teórico permite reconocer el proceso que el cuidador enfrenta para adoptar su rol en el cuidado al paciente crónico y orientar posibles intervenciones de enfermería para favorecer una transición saludable.

Resumo Objetivo: apresentar uma proposta de teoria de uma situação específica sobre a adoção do papel de cuidador do paciente crônico. Materiais e métodos: com base na estratégia integrativa de Meleis e Im, foram utilizadas múltiplas fontes de informação para o desenvolvimento desta teoria. Resultados: esta teoria prescritiva deriva da teoria de médio alcance das transições de Meleis, a partir de uma exaustiva revisão da literatura e da experiência prática e de pesquisa dos autores. As informações foram integradas em conceitos centrais como: transição do cuidador, insuficiência do papel do cuidador, natureza da transição, condições de transição, cuidados de transição de enfermagem para o cuidador e transição saudável; com afirmações que indicam que a adoção do papel de cuidador influencia os padrões de resposta ou indicadores de resultados relacionados à qualidade de vida e à percepção de sobrecarga do cuidador; apresenta-se a descrição de um processo teórico e um indicador empírico denominado ROL. Conclusões: este desenvolvimento teórico permite reconhecer o processo que o cuidador enfrenta para adotar seu papel no cuidado ao paciente crônico e orientar possíveis intervenções de enfermagem para favorecer uma transição saudável.

Ansiedad, depresión, soledad y adopción del rol del cuidador de la persona en cuidado paliativo / Anxiety, depression, loneliness and role-taking in the caregiver of a person in palliative care

Introducción: Los cuidadores familiares de personas en cuidado paliativo (CP) se exponen continuamente a altas demandas de cuidado y a situaciones de angustia, lo que puede afectar su adopción del rol, ansiedad, depresión y percepción de soledad. Objetivo: Describir y correlacionar la ansiedad, depresión, soledad y adopción del rol en una muestra de cuidadores de personas en CP de Bogotá, Colombia.Materiales y métodos: Estudio cuantitativo transversal conducido en el primer semestre de 2021 con una muestra de 220 cuidadores familiares principales de personas en CP. Se usaron los instrumentos ROL, HADS y UCLA para medir la adopción del rol del cuidador, ansiedad y depresión, y soledad respectivamente. Fueron usados coeficientes de correlación de Pearson y modelos de regresión lineal para analizar la relación entre las variables. Resultados: El 75 % de las personas en CP tenían cáncer, el 63,2 % con índice de Karnofsky de 30 y con una edad promedio de 69,4 años. El 81,8 % de los cuidadores fueron mujeres, con edad promedio de 47,7 años, el 85,5 % cuida a la persona desde el momento del diagnóstico con una dedicación promedio de 20 h diarias de cuidado; además el 34,2 % se autorreportó enfermo. Los cuidadores que tuvieron menores puntajes de adopción del rol tendieron a presentar mayores niveles de ansiedad, depresión y soledad (p < 0,05). Conclusión: Se requieren intervenciones de cuidado transicional de cuidador familiar de la persona en CP dado su mayor riesgo de presentar soledad, ansiedad y depresión, que promuevan una adopción del rol satisfactoria y que, con ello, mejore los resultados en estos. (AU)

Introduction: Family caregivers of people in palliative care (PC) are continually exposed to high demands for care and situations of distress, which can affect their adoption of the role, causing anxiety, depression, and a perception of loneliness. Aim: To describe and correlate anxiety, depression, loneliness, and role adoption in a sample of caregivers of people in PC in Bogotá, Colombia. Materials and methods: A cross-sectional quantitative study was conducted in the first half of 2021 with a sample of 220 main family caregivers of people in PC. The ROL, HADS, and UCLA instruments were used to measure role-taking, anxiety, depression, and loneliness, respectively. Pearson’s correlation coefficients and linear regression models were used to analyze the relationship between variables. Results: 75 % of people in PC had cancer, 63.2 % with a Karnofsky index of 30 and a mean age of 69.4 years; 81.8 % of the caregivers were women, with an average age of 47.7 years; 85.5 % cared for the patient from the time of diagnosis, with an average dedication of 20 hours of care per day. In addition, 34.2 % self-reported illness. Caregivers who had lower role-adoption scores tended to have higher levels of anxiety, depression, and loneliness (p < 0.05). Conclusion: Transitional care interventions are needed for the family caregivers of people in PC given their greater risk of having loneliness, anxiety, and depression, to promote satisfactory role-taking and thus improve their results. (AU)

Multiomics characterization of methicillin-resistant Staphylococcus aureus (MRSA) isolates with heterogeneous intermediate resistance to vancomycin (hVISA) in Latin America.

BACKGROUND: Heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA) compromise the clinical efficacy of vancomycin. The hVISA isolates spontaneously produce vancomycin-intermediate Staphylococcus aureus (VISA) cells generated by diverse and intriguing mechanisms. OBJECTIVE: To characterize the biomolecular profile of clinical hVISA applying genomic, transcriptomic and metabolomic approaches. METHODS: 39 hVISA and 305 VSSA and their genomes were included. Core genome-based Bayesian phylogenetic reconstructions were built and alterations in predicted proteins in VISA/hVISA were interrogated. Linear discriminant analysis and a Genome-Wide Association Study were performed. Differentially expressed genes were identified in hVISA-VSSA by RNA-sequencing. The undirected profiles of metabolites were determined by liquid chromatography and hydrophilic interaction in six CC5-MRSA. RESULTS: Genomic relatedness of MRSA associated to hVISA phenotype was not detected. The change Try38 → His in Atl (autolysin) was identified in 92% of the hVISA. We identified SNPs and k-mers associated to hVISA in 11 coding regions with predicted functions in virulence, transport systems, carbohydrate metabolism and tRNA synthesis. Further, capABCDE, sdrD, esaA, esaD, essA and ssaA genes were overexpressed in hVISA, while lacABCDEFG genes were downregulated. Additionally, valine, threonine, leucine tyrosine, FAD and NADH were more abundant in VSSA, while arginine, glycine and betaine were more abundant in hVISA. Finally, we observed altered metabolic pathways in hVISA, including purine and pyrimidine pathway, CoA biosynthesis, amino acid metabolism and aminoacyl tRNA biosynthesis. CONCLUSIONS: Our results show that the mechanism of hVISA involves major changes in regulatory systems, expression of virulence factors and reduction in glycolysis via TCA cycle. This work contributes to the understanding of the development of this complex resistance mechanism in regional strains.

Molecular mechanisms leading to ceftolozane/tazobactam resistance in clinical isolates of Pseudomonas aeruginosa from five Latin American countries.

Objectives: Identify molecular mechanisms responsible for the in vitro non-susceptibility to ceftolozane/tazobactam (TOL) in a group of 158 clinical isolates of Pseudomonas aeruginosa from five Latin American countries collected before the introduction of TOL into the clinical practice. Methods: Clinical isolates of P. aeruginosa (n = 504) were collected between January 2016 and October 2017 from 20 hospitals located in Argentina, Brazil, Chile, Colombia, and Mexico. Minimum inhibitory concentrations (MICs) to TOL were determined by standard broth microdilution and interpreted according to CLSI breakpoints. Initially, production of carbapenemases in TOL non-susceptible isolates was assessed by Rapidec® followed by qPCR to detect bla KPC, bla NDM-1, bla VIM, and bla IMP. Illumina® WGS was performed for isolates in which non-susceptibility to TOL was not mediated by carbapenemases. Results: A total of 158 (31.3%) isolates were non-susceptible to TOL. In 74 (46.8%) of these isolates, non-susceptibility to TOL was explained by the production of at least one carbapenemase. WGS revealed that some isolates carried ESBLs, mutated bla PDC and ampD, associated with decreased susceptibility to TOL. Conclusion: Substitutions found in PDC and carbapenemase production were the most common presumed mechanisms of resistance to TOL detected in this study. This study shows that epidemiological surveillance is warranted to monitor the emergence of novel mechanisms of resistance to TOL that might compromise its clinical utility.