Caveats of chimpanzee ChAdOx1 adenovirus-vectored vaccines to boost anti-SARS-CoV-2 protective immunity in mice.

Several COVID-19 vaccines use adenovirus vectors to deliver the SARS-CoV-2 spike (S) protein. Immunization with these vaccines promotes immunity against the S protein, but against also the adenovirus itself. This could interfere with the entry of the vaccine into the cell, reducing its efficacy. Herein, we evaluate the efficiency of an adenovirus-vectored vaccine (chimpanzee ChAdOx1 adenovirus, AZD1222) in boosting the specific immunity compared to that induced by a recombinant receptor-binding domain (RBD)-based vaccine without viral vector. Mice immunized with the AZD1222 human vaccine were given a booster 6 months later, with either the homologous vaccine or a recombinant vaccine based on RBD of the delta variant, which was prevalent at the start of this study. A significant increase in anti-RBD antibody levels was observed in rRBD-boosted mice (31-61%) compared to those receiving two doses of AZD1222 (0%). Significantly higher rates of PepMix™- or RBD-elicited proliferation were also observed in IFNγ-producing CD4 and CD8 cells from mice boosted with one or two doses of RBD, respectively. The lower efficiency of the ChAdOx1-S vaccine in boosting specific immunity could be the result of a pre-existing anti-vector immunity, induced by increased levels of anti-adenovirus antibodies found both in mice and humans. Taken together, these results point to the importance of avoiding the recurrent use of the same adenovirus vector in individuals with immunity and memory against them. It also illustrates the disadvantages of ChAdOx1 adenovirus-vectored vaccine with respect to recombinant protein vaccines, which can be used without restriction in vaccine-booster programs. KEY POINTS: • ChAdOx1 adenovirus vaccine (AZD1222) may not be effective in boosting anti-SARS-CoV-2 immunity • A recombinant RBD protein vaccine is effective in boosting anti-SARS-CoV-2 immunity in mice • Antibodies elicited by the rRBD-delta vaccine persisted for up to 3 months in mice.

Anti-toxoplasma activity and DNA-binding of copper(II) and zinc(II) coordination compounds with 5-nitroimidazole-based ligands.

Tetrahedral copper(II) and zinc(II) coordination compounds from 5-nitroimidazole derivatives, viz. 1-(2-chloroethyl)-2-methyl-5-nitroimidazole (cenz) and ornidazole 1-(3-chloro-2-hydroxypropyl)-2-methyl-5-nitroimidazole (onz), were synthesized and spectroscopically characterized. Their molecular structures were determined by X-ray diffraction studies. The complexes [Cu(onz)2X2], [Zn(onz)2X2], [Cu(cenz)2X2] and [Zn(cenz)2X2] (X- = Cl, Br), are stable in solution and exhibit positive LogD7.4 values that are in the range for molecules capable of crossing the cell membrane via passive difussion. Their biological activity against Toxoplasma gondi was investigated, and IC50 and lethal dose (LD50) values were determined. The ornidazole copper(II) compounds showed very good antiparasitic activity in its tachyzoite morphology. The interaction of the coordination compounds with DNA was examined by circular dichroism, fluorescence (using intercalating ethidium bromide and minor groove binding Hoechst 33258) and UV-Vis spectroscopy. The copper(II) compounds interact with the minor groove of the biomolecule, whereas weaker electrostatic interactions take place with the zinc(II) compounds. The spectroscopic data achieved for the two series of complexes (namely with copper(II) and zinc(II) as metal center) agree with the respective DNA-damage features observed by gel electrophoresis.

A Novel Pathogenic Variant in the MN1 Gene in a Patient Presenting with Rhombencephalosynapsis and Craniofacial Anomalies, Expanding MN1 C-terminal Truncation Syndrome.

Meningioma-1 is a transcription activator that regulates mammalian palate development and is required for appropriate osteoblast proliferation, motility, differentiation, and function. Microdeletions involving the MN1 gene have been linked to syndromes including craniofacial anomalies, such as Toriello-Carey syndrome. Recently, truncating variants in the C-terminal portion of the MN1 transcriptional factor have been linked to a characteristic and distinct phenotype presenting with craniofacial anomalies and partial rhombencephalosynapsis, a rare brain malformation characterized by midline fusion of the cerebellar hemispheres with partial or complete loss of the cerebellar vermis. It has been called MN1 C-terminal truncation (MCTT) syndrome or CEBALID (Craniofacial defects, dysmorphic Ears, Brain Abnormalities, Language delay, and Intellectual Disability) and suggested to be caused by dominantly acting truncated protein MN1 instead of haploinsufficiency. As a proto-oncogene, MN1 is also involved in familial meningioma. In this study, we present a novel case of MCTT syndrome in a female patient presenting with craniofacial anomalies and rhombencephalosynapsis, harboring a de novo pathogenic variant in the MN1 gene: c.3686_3698del, p.(Met1229Argfs*87).

Effects of Etomidate on Postintubation Hypotension, Inflammatory Markers, and Mortality in Critically Ill Patients with COVID-19: An International, Multicenter, Retrospective Study.

OBJECTIVE: To evaluate the association of etomidate with postintubation hypotension, inflammation, and mortality in critically ill patients with COVID-19. DESIGN: International, multicenter, retrospective study. PARTICIPANTS: Critically ill patients hospitalized specifically for COVID-19 from three major academic institutions in the US and Europe. MAIN OUTCOME AND MEASURES: Patients were allocated into the etomidate (ET) group or another induction agent (OA) group. The primary outcome was postintubation hypotension. Secondary outcomes included postintubation inflammatory status, in-hospital mortality, and mortality at 30 days. RESULTS: 171 patients with a median age of 68 (IQR 58-73) years were included (ET, n = 98; OA, n = 73). Etomidate was associated with lower postintubation mean arterial pressure [74.33 (64-85) mm Hg versus 81.84 (69.75-94.25) mm Hg, p = 0.005] compared to other agents. No statistically significant differences were generally observed in inflammatory markers between the two groups at 7- and 14-days after admission to the intensive care unit. In-hospital mortality [77 (79%) versus 41 (56%), p = 0.003] and mortality at 30-days [78 (80%) versus 43 (59%), p = 0.006] were higher in the ET group. In multivariate logistic regression analysis, only etomidate (p = 0.009) and postintubation mean arterial pressure (p < 0.001) had a statistically significant effect on mortality, in contrast to stress-dose steroids (p = 0.301), after adjusting for creatinine (p = 0.695), blood urea nitrogen (p = 0.153), age (p = 0.055), oxygen saturation of hemoglobin (SpO2) (p = 0.941), and fraction of inspired oxygen (FiO2) (p = 0.712). CONCLUSIONS: Administration of a single-bolus dose of etomidate in critically ill patients with COVID-19 is associated with lower postintubation mean arterial pressure and higher in-hospital and 30-day mortality compared to other induction agents.

Naturally occurring deamidated triosephosphate isomerase is a promising target for cell-selective therapy in cancer.

Human triosephosphate isomerase (HsTIM) is a central glycolytic enzyme and is overexpressed in cancer cells with accelerated glycolysis. Triple-negative breast cancer is highly dependent on glycolysis and is typically treated with a combination of surgery, radiation therapy, and chemotherapy. Deamidated HsTIM was recently proposed as a druggable target. Although thiol-reactive drugs affect cell growth in deamidated HsTIM-complemented cells, the role of this protein as a selective target has not been demonstrated. To delve into the usefulness of deamidated HsTIM as a selective target, we assessed its natural accumulation in breast cancer cells. We found that deamidated HsTIM accumulates in breast cancer cells but not in noncancerous cells. The cancer cells are selectively programmed to undergo cell death with thiol-reactive drugs that induced the production of methylglyoxal (MGO) and advanced glycation-end products (AGEs). In vivo, a thiol-reactive drug effectively inhibits the growth of xenograft tumors with an underlying mechanism involving deamidated HsTIM. Our findings demonstrate the usefulness of deamidated HsTIM as target to develop new therapeutic strategies for the treatment of cancers and other pathologies in which this post translationally modified protein accumulates.

AS1411 Nucleolin-Specific Binding Aptamers Reduce Pathological Angiogenesis through Inhibition of Nucleolin Phosphorylation.

Proliferative retinopathies produces an irreversible type of blindness affecting working age and pediatric population of industrialized countries. Despite the good results of anti-VEGF therapy, intraocular and systemic complications are often associated after its intravitreal use, hence novel therapeutic approaches are needed. The aim of the present study is to test the effect of the AS1411, an antiangiogenic nucleolin-binding aptamer, using in vivo, ex vivo and in vitro models of angiogenesis and propose a mechanistic insight. Our results showed that AS1411 significantly inhibited retinal neovascularization in the oxygen induced retinopathy (OIR) in vivo model, as well as inhibited branch formation in the rat aortic ex vivo assay, and, significantly reduced proliferation, cell migration and tube formation in the HUVEC in vitro model. Importantly, phosphorylated NCL protein was significantly abolished in HUVEC in the presence of AS1411 without affecting NFκB phosphorylation and -21 and 221-angiomiRs, suggesting that the antiangiogenic properties of this molecule are partially mediated by a down regulation in NCL phosphorylation. In sum, this new research further supports the NCL role in the molecular etiology of pathological angiogenesis and identifies AS1411 as a novel anti-angiogenic treatment.

Anti-proliferative, pro-apoptotic and anti-invasive effect of the copper coordination compound Cas III-La through the induction of reactive oxygen species and regulation of Wnt/ß-catenin pathway in glioma.

Gliomas are the most aggressive neoplasms that affect the central nervous system, being glioblastoma multiforme (GBM) the most malignant. The resistance of GBM to therapies is attributed to its high rate of cell proliferation, angiogenesis, invasion, and resistance to apoptosis; thus, finding alternative therapeutic approaches is vital. In this work, the anti-proliferative, pro-apoptotic, and anti-invasive effect of the copper coordination compound Casiopeina III-La (Cas III-La) on human U373 MG cells was determined in vitro and in vivo. Our results indicate that Cas III-La exerts an anti-proliferative effect, promoting apoptotic cell death and inactivating the invasive process by generating reactive oxygen species (ROS), inactivating GSK3ß, activating JNK and ERK, and promoting the nuclear accumulation of ß-catenin. The inhibition of ROS generation by N-acetyl-l-cysteine not only recovered cell migration and viability, but also reduced ß-catenin accumulation and JNK and ERK activation. Additionally, Cas III-La significantly reduced tumor volume, cell proliferation and mitotic indices, and increased the apoptotic index in mice xenotransplanted with U373 glioma cells. Thus, Cas III-La is a promising agent to treat GBM.

Coordination compounds with heterocyclic ester derivatives. Structural characterization and anti-proliferative activity.

A series of new coordination compounds of cobalt(II), copper(II) and zinc(II) with heterocyclic ester derivatives (ethyl 4-methyl-5-imidazole-carboxylate (emizco), 1-(2-(phenylsulphonyl)ethyl)-4-imidazole carboxylate (semizco)) and methyl 5-(propylthio)-2-benzimidazolecarbamate (albendazole, abz) were synthesized. They were fully characterized by different techniques such as IR, UV-Vis-NIR, elemental analysis, molar conductivity and magnetic susceptibility. Additionally, X-ray crystal structures of semizco and its [Co(semizco)2Cl2]·2CH3CN 10, [Co(smmizco)2Br2]·2CH3CN 11 and [Cu(semizco)2Br2] 15 coordination compounds are analyzed. These compounds present lone pair SO⋯π interactions between the sulfone and the imidazolic ring. These ligands showed three coordination modes: monodentate, through an imidazolic nitrogen atom, or a bidentate chelating mode by a nitrogen and an oxygen atom from the ester group. The different coordination modes and the number of coordinated ligands gave rise to tetrahedral and octahedral compounds, or for [Cu(semizco)(µ-Br)Br]n·0.5H2O 7 a square base pyramidal geometry. A cytotoxic study was carried out with the free ligands and their copper(II) and zinc(II) halide coordination compounds on HeLa (cervix-uterine), MCF-7 (breast), HCT-15 (colon), PC3 (prostate) human carcinoma cell lines and L929 mouse fibroblast (healthy cells). A TUNEL assay (terminal deoxynucleotidyl transferase dUTP nick end labeling) was performed with the most active copper(II) compounds to determine if cell death was by apoptosis.

Toxicity Evaluation of a Novel Rapamycin Liposomal Formulation After Subconjunctival and Intravitreal Injection.

Purpose: Safety and toxicity evaluation of a novel, liposome-encapsulated rapamycin formulation, intended for autoimmune ocular disorders. Methods: The formulation was assessed by micronucleus polychromatic erythrocyte production, irritability by Hen's Egg Test-Chorioallantoic Membrane (HET CAM), sterility, and pyrogenicity testing. Subconjunctival (SCJ) and intravitreal (IVT) administration of the formulation were performed to evaluate subacute and acute toxicity, respectively. Differences between groups in biochemical and hematological parameters were evaluated by analysis of variance and t-tests. Numeric score was assigned to histopathological classification. Electroretinography (ERG) testing was also performed. Data were analyzed by a 1 way no parametric Kruskal-Wallis and the Mann-Whitney tests. Significance was considered when P < 0.05. Results: No significant toxicity directly related to the preparation was detected. Micronucleus count, mucous irritation score, and pyrogenicity results were negative. Pathology demonstrated no damage related to the formulation after SCJ injection. After IVT injection, only lens injury associated with technique was observed. Retinal function was also conserved in ERG. Conclusions: The preparation evaluated offers a good toxicity and safety profile when injected in a SCJ or IVT manner in an animal model. A clinical trial conducted in humans is highly warranted, as it could reveal an alternative immunosuppressive treatment for ophthalmological immune-mediated pathologies.

Differential Susceptibility of Xylella fastidiosa Strains to Synthetic Bactericidal Peptides.

The kinetics of cell inactivation and the susceptibility of Xylella fastidiosa subspecies fastidiosa, multiplex, and pauca to synthetic antimicrobial peptides from two libraries (CECMEL11 and CYCLO10) were studied. The bactericidal effect was dependent on the relative concentrations of peptide and bacterial cells, and was influenced by the diluent, either buffer or sap. The most bactericidal and lytic peptide was BP178, an enlarged derivative of the amphipathic cationic linear undecapeptide BP100. The maximum reduction in survivors after BP178 treatment occurred within the first 10 to 20 min of contact and at micromolar concentrations (<10 µM), resulting in pore formation in cell membranes, abundant production of outer membrane vesicles, and lysis. A threshold ratio of 109 molecules of peptide per bacterial cell was estimated to be necessary to initiate cell inactivation. There was a differential susceptibility to BP178 among strains, with DD1 being the most resistant and CFBP 8173 the most susceptible. Moreover, strains showed a proportion of cells under the viable but nonculturable state, which was highly variable among strains. These findings may have implications for managing the diseases caused by X. fastidiosa.

State and life in Cuba: calibrating ideals and realities in a state-socialist system for food provision.

Based on our collective ethnography of Cuba's socialist system for the provision of state-subsidised food, this article explores manners in which the state weaves itself into the fabric of people's everyday lives in state-socialist society. Instituted by Cuba's revolutionary government in the early 1960s, Cuba's 'state system for provisioning' is still today the backbone of household subsistence, propelling individuals into direct daily relations with the state via its neighbourhood-level network of stores that distribute food catering to citizens' 'basic needs'. Our ethnography brings together a series of studies conducted by the members of our team in different parts of Havana, charting the most salient aspects of people's interaction with the state in this alimentary context. We argue that the state becomes pervasive in people's daily lives not just because it is present in so much of it, but also as the basic normative premise on which people interpret and evaluate everyday comportments in the interactions food provisioning involves. Life in state socialism involves the constant and intricate comparison of its own realities against the normative ideals the state purports to institute. These 'vernacular comparisons' between life and state, as we call them, are the 'local knowledge' of state socialism in Cuba.

A partir de nuestra etnografía colectiva del sistema del abastecimiento de alimentos subsidiados por el Estado cubano este artículo explora las formas en las que el estado se imbrica en el tejido de la vida cotidiana de las personas en el socialismo de estado. Instituido por el gobierno revolucionario cubano a principios de la década de 1960, el 'sistema estatal de abastecimiento' de Cuba es todavía hoy la espina dorsal de la subsistencia de los hogares, el cual impele a los individuos a establecer una relación cotidiana y directa con el estado a través de la red de establecimientos comerciales a nivel de barrio que distribuyen alimentos de acuerdo con las "necesidades básicas" de los ciudadanos. Nuestra etnografía reúne una serie de estudios llevados a cabo por los miembros de nuestro equipo en diferentes partes de La Habana, describiendo los aspectos más significativos de la interacción entre las personas y el estado en este contexto alimentario. Argumentamos que el estado se vuelve ubicuo en la vida cotidiana de las personas no sólo por estar presente en numerosos aspectos de la misma, sino también por ser el supuesto básico y normativo con el que la gente interpreta y evalúa sus comportamientos en las interacciones cotidianas relacionadas con el abastecimiento alimentario. La vida en el socialismo de estado involucra una constante e intrincada comparación entre los ideales normativos que el estado pretende institucionalizar y sus realidades. Estas 'comparaciones vernáculas' entre vida y estado, como las llamamos, son el 'conocimiento local' del socialismo de estado en Cuba.

S'appuyant sur une ethnographie collective du système socialiste cubain en matière d'approvisionnement de nourriture subventionné par l'État, cet article étudie la manière dont l'État s'immisce dans la vie quotidienne des gens, dans une société socialiste. Instauré à Cuba au début des années 1960 par le gouvernement révolutionnaire, le « système étatique d'approvisionnement ¼ constitue encore aujourd'hui l'épine dorsale de la subsistance des foyers, et pousse les individus à entretenir des relations quotidiennes directes avec l'État à travers son réseau de magasins de quartier, qui distribuent des aliments correspondant aux « besoins vitaux ¼ des citoyens. Nos travaux ethnographiques réunissent une série d'études, menées par les membres de notre équipe dans différents secteurs de La Havane, mettant en évidence les aspects les plus saillants de l'interaction entre les individus et l'État dans le domaine de l'alimentation. Nous soutenons que l'État pénètre dans la vie quotidienne des gens, non seulement parce qu'il y est presque omniprésent, mais aussi comme une prémisse normative fondamentale à partir de laquelle on interprète et évalue les comportements quotidiens dans les interactions faisant partie de l'approvisionnement alimentaire. La vie sous le socialisme étatique implique une comparaison complexe et constante entre ses propres réalités et les idéaux normatifs que l'État prétend instaurer. Ce que nous appelons les « comparaisons vernaculaires ¼ entre la vie et l'État composent la « connaissance locale ¼ du socialisme étatique à Cuba.

[Development of a tool to conduct family studies in primary health care]. / Estudio de familia en Atención Primaria: construcción y validación de una herramienta para la valoración familiar.

BACKGROUND: The Family and Community Health Model (MAIS) establishes the continuity of care as an essential principle. The Family Study, as a clinical strategy, allows to have sufficient and timely information and knowledge about users of health care services, facilitates their accompaniment and is a source of information to improve the quality of care and the management of health centers. AIM: To develop a tool to conduct family studies, devised by experts in Primary Health Care. MATERIAL AND METHODS: Using a qualitative method, an electronic Delphi was conducted on 24 experts on primary health care. Afterwards, the content validation was carried out with the participation of judges. RESULTS: The resulting tool considers two levels of family assessment. It allows to distinguish those families that would benefit from interventions of greater complexity than those derived from the usual care of health centers. CONCLUSIONS: The tool to perform family studies responds to the informational and continuity component of Continuity of Patient Care principle. It may be a proposal for the continuous improvement of Chilean primary care.

Estudio de familia en Atención Primaria: construcción y validación de una herramienta para la valoración familiar / Development of a tool to conduct family studies in primary health care

Background: The Family and Community Health Model (MAIS) establishes the continuity of care as an essential principle. The Family Study, as a clinical strategy, allows to have sufficient and timely information and knowledge about users of health care services, facilitates their accompaniment and is a source of information to improve the quality of care and the management of health centers. Aim: To develop a tool to conduct family studies, devised by experts in Primary Health Care. Material and Methods: Using a qualitative method, an electronic Delphi was conducted on 24 experts on primary health care. Afterwards, the content validation was carried out with the participation of judges. Results: The resulting tool considers two levels of family assessment. It allows to distinguish those families that would benefit from interventions of greater complexity than those derived from the usual care of health centers. Conclusions: The tool to perform family studies responds to the informational and continuity component of Continuity of Patient Care principle. It may be a proposal for the continuous improvement of Chilean primary care.

Exposure to bisphenol A: current levels from food intake are toxic to human cells.

In the present work, cell lines of different origin were exposed to BPA levels from food intake reported elsewhere. Specifically, we used an in vitro assay to determine cytotoxicity of BPA in three cell lines: MCF7 (breast cancer), PC3 (prostate cancer) and 3T3-L1 (mouse fibroblast). Cytotoxic effects were observed at concentrations higher than 50 µg/mL which is above the involuntary exposure level of BPA described before in fresh, canned and frozen foods and beverages. Furthermore, medial inhibitory concentrations (IC50) of 85.17 µg/mL and 88.48 µg/mL were observed for PC3 and 3T3-L1, respectively, and a slightly lower IC50 of 64.67 µg/mL for MCF7. These results highlight BPA's toxicity potential at current levels from food intake. The cell line-dependent divergent response to BPA reported herein is discussed.

Preclinical evidences of safety of a new synthetic adjuvant to formulate with the influenza human vaccine: absence of subchronic toxicity and mutagenicity.

Context: Influenza is a severe, life-threatening viral disease that can be prevented by vaccination. However, the anti-influenza human vaccine failed to show the required efficacy both in infants under 5 years old and in the elder population, who are among those with the highest risk of developing severe complications after influenza infection. Therefore, it is of high importance to improve the vaccine efficacy and ensure its safety in these susceptible populations. GK-1, a novel 18-aa peptide adjuvant, has been proved to increase the immunogenicity of the human influenza vaccine in both young and aged mice. Objective: A preclinical study of the toxicity profile of GK-1 following the World Health Organization guidelines to support its use was herein conducted. Material and methods: GK-1 was synthetically produced following Good Manufacturing Practices. The toxicological evaluation of GK-1 peptide was performed in rats after repeated dose-ranging trials by the subcutaneous route. The mutagenic potential of GK-1 was assessed by the micronucleus, chromosomal aberration, and Ames tests, in accordance with OECD Guidelines. Results: GK-1 did not show toxic effects at doses up to 12.5mg/kg, corresponding to 25 times the dose intended for human use. No indications of mutagenic potential were observed. GK-1 after dermal administration was well tolerated locally. Conclusion: The efficacy of GK-1 to improve influenza vaccine protection, along with the absence of toxicity and mutagenicity, as reported herein, support the evaluation of this peptide in a clinical trial as a novel adjuvant for human use.

Participación de los usuarios en las decisiones clínicas en la atención primaria de salud en Chile

[RESUMEN]. Objetivo. Describir la experiencia de participación en las decisiones clínicas desde la perspectiva de usuarios de Centros de Salud Familiar (CESFAM) de la Atención Primaria de Salud (APS). Métodos. Estudio de diseño cualitativo descriptivo; se realizaron grupos focales con usuarios de CESFAM del área sudeste de Santiago, Chile, y análisis temático de la información utilizando el programa Atlas.ti versión 6. Resultados. Se realizaron cinco grupos focales (n = 41). Los principales temas emergentes fueron el rol pasivo de los usuarios en las decisiones y la toma de decisión delegada, basada en la confianza en el profesional. El rol pasivo de los usuarios limita las oportunidades de participación en las decisiones clínicas y mantiene el poder en los profesionales de la salud. A pesar de ello, el establecimiento de una alianza terapéutica les permita sentirse tratados como personas únicas, escuchados y respetados por los profesionales, lo que asegura que las decisiones tomadas por el equipo de salud son confiables, pues velan por sus reales intereses. Conclusión. La participación de los usuarios en los encuentros clínicos es aún escasa en el país. Sin embargo, potenciar esta participación es esencial para aumentar la satisfacción usuaria y promover un cuidado centrado en la persona.

[ABSTRACT]. Objective. Describe users’ experience with participation in clinical decision-making at Family Health Centers (CESFAM) in the Primary Health Care (PHC) system. Methods. Qualitative descriptive study. Focus groups made up of CESFAM users were held in southeastern Santiago, Chile, and the information was thematically analyzed using Atlas.ti version 6® software. Results. Five focus groups were held (n = 41). The main themes that emerged from the discussions were the passive role of users in decisions and delegated decision-making, based on their trust in the health professional. Users’ passive role limits their opportunities for participation in clinical decision-making, ceding power to the health professional. However, establishing a therapeutic partnership allows users to feel that they are being treated as unique individuals whom the professional listens to and respects, ensuring that the decisions of the health team can be trusted, since they look out for the users’ real interests. Conclusion. Users’ participation in clinical encounters is still limited in Chile. However, bolstering that participation is essential for increasing user satisfaction and promoting people-centered care.

[RESUMO]. Objetivo. Descrever a experiência de participação nas decisões clínicas dos usuários dos Centros de Saúde Familiar (CESFAM) de atenção primária à saúde. Métodos. Estudo qualitativo descritivo conduzido em grupos de discussão formados por usuários dos CESFAM da região sudeste da cidade de Santiago, no Chile. Foi realizada uma análise temática das informações com o uso do programa de software ATLAS.ti versão 6. Resultados. Foram formados cinco grupos de discussão (n = 41). Os principais tópicos abordados foram o papel passivo dos usuários nas decisões e a tomada de decisão delegada aos profissionais na base da confiança. O papel passivo restringe as oportunidades de participação dos usuários nas decisões clínicas e mantém o poder nas mãos dos profissionais da saúde. Apesar disso, ao ser criada uma aliança terapêutica, os usuários se sentem tratados como indivíduos únicos que são ouvidos e respeitados pelos profissionais, o que assegura que as decisões tomadas pela equipe de saúde sejam confiáveis porque protegem os reais interesses dos usuários. Conclusão. Os usuários ainda têm pouca participação nas interações clínicas no Chile. Porém, é fundamental reforçar esta participação para melhorar a satisfação do usuário e promover uma atenção mais centrada na pessoa.

Formación y competencias para los equipos de atención primaria desde la mirada de expertos chilenos

[RESUMEN]. Objetivo. Describir las competencias para equipos de atención primaria en salud (APS) en distintos tópicos vinculados a la atención directa del usuario y a la gestión de los centros de salud primarios, de acuerdo a la percepción de expertos chilenos en APS. Métodos. Estudio de diseño mixto. Se realizó un Delphi electrónico con 29 expertos nacionales en APS. Resultados. Se propone una matriz de competencias específicas vinculada al trabajo directo con familias y a la gestión del centro de salud priorizados en tres niveles. Los expertos concuerdan que se requiere una masa crítica de profesionales que cuenten con competencias que le conciernen a la APS. Conclusiones. El reto de reorganizar los sistemas de salud en torno a una APS fuerte y de calidad solo puede lograrse con la participación de profesionales que comprendan y practiquen los atributos y principios fundamentales de la APS. Los resultados de este estudio dan cuenta de un perfil de competencias para profesionales de APS alineado con recomendaciones internacionales alcanzable a través de estrategias de educación continua.

[ABSTRACT]. Objective. To describe the competencies for primary health care teams (PHC) in different topics related to the direct care of the user and the management of primary health centers, according to the perception of Chilean experts in PHC. Methods. Mixed design studio. An electronic Delphi method was conducted with 29 national experts in APS. Results. A matrix of specific competences related to direct work with families and to the management of the health center prioritized in three levels is proposed. Experts agreed that a critical mass of professionals with competencies in PHC is required. Conclusions. The challenge of reorganizing health systems around a strong and quality PHC can only be achieved with the participation of professionals who understand and practice the attributes and fundamental principles of PHC. The results of this study show a competency profile for PHC professionals aligned with international recommendations achievable through continuous education strategies.

[RESUMO]. Objetivo. Descrever as habilidades para equipes de atenção primária à saúde (APS) sobre vários tópicos vinculados com a atenção direta do usuário e gestão de centros de saúde, de acordo com a percepção de especialistas chilenos na APS. Métodos. Estudo de desenho misto. Foi realizado um Delphi eletrônico com 29 especialistas nacionais em APS. Resultados. É proposta uma matriz de competências específicas vinculada ao trabalho direto com famílias e à gestão do centro de saúde priorizados em três níveis. Os especialistas concordam que se requer uma massa crítica de profissionais que contem com competências em APS. Conclusões. O desafio de reorganizar os sistemas de saúde em torno de uma APS forte e de qualidade só se pode conseguir com a participação de profissionais que entendem e pratiquem os atributos e os princípios fundamentais da APS. Os resultados deste estudo mostram um perfil de competências para profissionais de APS alinhados com recomendações internacionais que podem ser alcançadas através de estratégias de educação contínua.

Estándares de calidad en la cirugía oncológica pancreática en España / Outcome quality standards in pancreatic oncologic surgery in Spain

INTRODUCCIÓN: Identificar los estándares de calidad en la cirugía oncológica es un reto complejo necesario para poder mejorar los resultados quirúrgicos. A diferencia de lo que ocurre en otros tumores, no existen unos estándares de calidad bien definidos en el cáncer de páncreas. El objetivo es identificar los indicadores de calidad en la cirugía pancreática oncológica en España, así como sus límites de variabilidad. MÉTODOS: Los indicadores de calidad se han seleccionado a partir de las guías de práctica clínica, conferencias de consenso, revisiones y publicaciones de ámbito nacional sobre cirugía pancreática oncológica entre los años 2000-2016. Los márgenes de variabilidad para cada indicador se obtienen mediante estadística de control de procesos y gráficas de representación, teniendo en cuenta el tamaño de las series. Los límites de variabilidad se establecen a partir de la media y los intervalos de confianza al 95 y al 99,8%. RESULTADOS: Se han determinado los siguientes indicadores con sus medias y límites de calidad aceptables: tasa de resecabilidad 71% (> 58%), morbilidad 58% (< 73%), mortalidad 4% (< 10%), tasa de fístula biliar 6% (< 14%), tasa de fístula pancreática 18% (< 29%), hemorragia 11% (< 21%), tasa de reintervención 11% (< 20%) y estancia media (< 21 días). CONCLUSIONES: El número de series publicadas es muy escaso y presentan limitaciones metodológicas importantes. Entre los indicadores seleccionados, los límites de calidad de morbimortalidad han resultado más elevados que los obtenidos en los estándares internacionales. Es necesario que los cirujanos pancreáticos españoles adopten unos criterios homogéneos consensuados de los indicadores y su definición que permitan comparar sus resultados

INTRODUCTION: To establish quality standards in oncologic surgery is a complex but necessary challenge to improve surgical outcomes. Unlike other tumors, there are no well-defined quality standards in pancreatic cancer. The aim of this study is to identify quality indicators in pancreatic oncologic surgery in Spain as well as their acceptable limits of variability. METHODS: Quality indicators were selected based on clinical practice guidelines, consensus conferences, reviews and national publications on oncologic pancreatic surgery between the years 2000 and 2016. Variability margins for each indicator have been determined by statistical process control techniques and graphically represented with the 99.8 and 95% confidence intervals above and below the weighted average according to sample size. RESULTS: The following indicators have been determined with their weighted average and acceptable quality limits: resectability rate 71% (> 58%), morbidity 58% (< 73%), mortality 4% (< 10%), biliary leak 6% (< 14%), pancreatic fistula rate 18% (< 29%), hemorrhage 11% (< 21%), reoperation rate 11% (< 20%) and mean hospital stay (< 21 days). CONCLUSIONS: To date, few related series have been published, and they present important methodological limitations. Among the selected indicators, the morbidity and mortality quality limits have come out higher than those obtained in international standards. It is necessary for Spanish pancreatic surgeons to adopt homogeneous criteria regarding indicators and their definitions to allow for the comparison of their results

Outcome quality standards in pancreatic oncologic surgery in Spain. / Estándares de calidad en la cirugía oncológica pancreática en España.

INTRODUCTION: To establish quality standards in oncologic surgery is a complex but necessary challenge to improve surgical outcomes. Unlike other tumors, there are no well-defined quality standards in pancreatic cancer. The aim of this study is to identify quality indicators in pancreatic oncologic surgery in Spain as well as their acceptable limits of variability. METHODS: Quality indicators were selected based on clinical practice guidelines, consensus conferences, reviews and national publications on oncologic pancreatic surgery between the years 2000 and 2016. Variability margins for each indicator have been determined by statistical process control techniques and graphically represented with the 99.8 and 95% confidence intervals above and below the weighted average according to sample size. RESULTS: The following indicators have been determined with their weighted average and acceptable quality limits: resectability rate 71% (>58%), morbidity 58% (<73%), mortality 4% (<10%), biliary leak 6% (<14%), pancreatic fistula rate 18% (<29%), hemorrhage 11% (<21%), reoperation rate 11% (<20%) and mean hospital stay (<21 days). CONCLUSIONS: To date, few related series have been published, and they present important methodological limitations. Among the selected indicators, the morbidity and mortality quality limits have come out higher than those obtained in international standards. It is necessary for Spanish pancreatic surgeons to adopt homogeneous criteria regarding indicators and their definitions to allow for the comparison of their results.

[User Participation in Clinical Decision-making in Primary Health Care in ChileParticipação dos usuários nas decisões clínicas na atenção primária à saúde no Chile]. / Participación de los usuarios en las decisiones clínicas en la atención primaria de salud en Chile.

OBJECTIVE: Describe users' experience with participation in clinical decision-making at Family Health Centers (CESFAM) in the Primary Health Care (PHC) system. METHODS: Qualitative descriptive study. Focus groups made up of CESFAM users were held in southeastern Santiago, Chile, and the information was thematically analyzed using Atlas.ti version 6® software. RESULTS: Five focus groups were held (n = 41). The main themes that emerged from the discussions were the passive role of users in decisions and delegated decision-making, based on their trust in the health professional. Users' passive role limits their opportunities for participation in clinical decision-making, ceding power to the health professional. However, establishing a therapeutic partnership allows users to feel that they are being treated as unique individuals whom the professional listens to and respects, ensuring that the decisions of the health team can be trusted, since they look out for the users' real interests. CONCLUSION: Users' participation in clinical encounters is still limited in Chile. However, bolstering that participation is essential for increasing user satisfaction and promoting people-centered care.

OBJETIVO: Descrever a experiência de participação nas decisões clínicas dos usuários dos Centros de Saúde Familiar (CESFAM) de atenção primária à saúde. MÉTODOS: Estudo qualitativo descritivo conduzido em grupos de discussão formados por usuários dos CESFAM da região sudeste da cidade de Santiago, no Chile. Foi realizada uma análise temática das informações com o uso do programa de software ATLAS.ti® versão 6. RESULTADOS: Foram formados cinco grupos de discussão (n = 41). Os principais tópicos abordados foram o papel passivo dos usuários nas decisões e a tomada de decisão delegada aos profissionais na base da confiança. O papel passivo restringe as oportunidades de participação dos usuários nas decisões clínicas e mantém o poder nas mãos dos profissionais da saúde. Apesar disso, ao ser criada uma aliança terapêutica, os usuários se sentem tratados como indivíduos únicos que são ouvidos e respeitados pelos profissionais, o que assegura que as decisões tomadas pela equipe de saúde sejam confiáveis porque protegem os reais interesses dos usuários. CONCLUSÃO: Os usuários ainda têm pouca participação nas interações clínicas no Chile. Porém, é fundamental reforçar esta participação para melhorar a satisfação do usuário e promover uma atenção mais centrada na pessoa.