La utilización de prácticas inefectivas en Atención Primaria: Opinión de los profesionales.

Objetivo: Estimar la frecuencia en el uso de prácticas inefectivas en el ámbito de la Atención Primaria, en base a la opinión de profesionales clínicos que trabajen en ese ámbito, así como valorar la importancia que los médicos de atención primaria conceden a la utilización de esas prácticas inefectivas en su ámbito profesional, las consecuencias que pueden estar ocasionando y los factores que pueden estar contribuyendo a su mantenimiento. Material y métodos: A partir de la lista de intervenciones consideradas infectivas por algunas organizaciones internacionales (Choosing – Wisely) en el ámbito de la atención primaria se diseñó una encuesta de opinión sobre la utilización de dichas intervenciones que fue administrada por vía “on line” a una muestra de conveniencia compuesta por 575 profesionales de la atención primaria seleccionados a partir de las direcciones de contacto que constaban en los artículos publicados en los dos últimos años de las revistas Atención Primaria y Semergen. Se analizaron las frecuencias de respuesta y las posibles diferencias en relación con las características sociodemográficas de los encuestados mediante los test de Chi cuadrado (variables cualitativas) y Kruskal-Wallis (variables cuantitativas). Resultados: La tasa de respuesta fue del 37% (n=212), en su mayoría eran varones (59%), de entre 50 y 50 años (42,0%), con más de 20 años de experiencia profesional (50,5%) y que acostumbran a leer más de 20 artículos científicos al año (69,7%). Para el 70,6 % [IC95%: 64,5-73,7] de los encuestados el problema de la sobremedicación, el sobrediagnóstico o sobretratamiento es frecuente o muy frecuente en el ámbito de la AP y el 31% [IC95%: 24,7-37,3] manifestaba que más del 25% de las prácticas de AP deberían dejar de hacerse por inefectivas. En conjunto valoraron la importancia de este problema en su ámbito de trabajo con una media de 7,3 (DE=1,8) sobre 10, siendo esta valoración significativamente menor (p ≤ 0,01) en quienes llevaban trabajando más de 20 años (6,9; DE=1,9). Señalaron como sus principales consecuencias la puesta en peligro de la sostenibilidad del sistema (48,1%; IC95%: 41,2-54,9) y el potencial daño a los pacientes (32,1%; IC95%: 25,7-38,5) y como principales factores que contribuyen a su mantenimiento la acción de los propios pacientes (28%; IC95%: 22,6-35,0), la carga de trabajo (26,4%; IC95%: 20,3-32,5) y la falta de formación continuada (19,3%; IC95%: 13,9-24,7). No había diferencias significativas en las respuestas con ninguna variable sociodemográfica analizada. Las intervenciones clínicas, según los encuestados, que presentan un mayor grado de utilización inadecuada son la prescripción de antibióticos en procesos infecciosos de probable origen vírico, la periodicidad del cribado del cáncer de cuello uterino, el control estrecho mediante fármacos de la diabetes tipo II en pacientes 65 años y la utilización de benzodiacepinas, hipnóticos y antipsicóticos en pacientes ancianos o el uso de analgésicos en pacientes con hipertensión o insuficiencia renal. Conclusiones: La utilización de intervenciones inefectivas en atención primaria es apreciado como un problema muy relevante por los profesionales que trabajan en este ámbito; afectaría a muchos de los pacientes atendidos y a muchas de las prácticas actualmente realizadas en los centros de salud y podría estar poniendo en peligro la sostenibilidad del sistema sanitario y causando daños a los pacientes. Deberían llevarse a cabo programas de mejora centrados en ciertas intervenciones identificadas con un mayor nivel de uso inadecuado para reducir el impacto de este problema en atención primaria

Efectos de componentes del lumen intestinal sobre células de adenocarcinoma de colon humano. Apoptosis inducida por ácidos biliares y regulación de la transcripción génica por butirato

Environmental factors are strongly involved in the development of colon cancer. Among them, diet and nutritional habits constitute the most determinant causes in the appearance of sporadic colorectal cancer. The continuous exposure to high concentrations of bile acids in individuals with a fat-rich diet leads to DNA damage and may allow selective growth of cells resistant to the cytotoxic effects of these agents, increasing the risk of tumor development. In this regard, we have studied the effect of DCA and CDCA treatments in butyrate-sensitive BCS-TC2 human colon adenocarcinoma cells, as well as in butyrate-resistant BCS-TC2.BR2 cells. We have confirmed that these bile acids promote cell death in both cell lines, being this effect stronger in BCS-TC2 cells. DCA and CDCA trigger apoptosis after short treatment times (< 2h), as observed by several characteristic apoptotic features, such as cell detachment, internucleosomal DNA degradation, caspase activation and loss of membrane asymmetry. We have confirmed that these events occur in BCS-TC2 cells through the activation of different membrane-associated enzymes [NAD(P)H oxidases and PLA2] which leads to an increase of reactive oxygen species that eventually triggers the mitochondrial apoptotic pathway. The activation of caspase-3 by the apoptosome activates Bax via cleavage of Bcl-2, thus generating a feedback loop that amplifies the apoptotic signal. On the other hand, we have observed that the mechanisms of apoptosis triggered by bile acids in butyrate-resistant cells are similar to that observed in butyrate-sensitive cells. However, BCS-TC2.BR2 cells express higher levels of the antiapoptotic protein Bcl-2 that prevent the activation of Bax. Thus, resistant cells overcome the proapoptotic feedback loop observed in BCS-TC2 cells..

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Upregulation of Annexin A1 Expression by Butyrate in Human Colon Adenocarcinoma Cells: Role of p53, NF-Y, and p38 Mitogen-Activated Protein Kinase

Annexin A1 is a member of a phospholipid and calcium binding family of proteins; it is involved in anti-inflammation and in the regulation of differentiation, proliferation, and apoptosis. Here, we show the existence of a functional binding site for the tumor suppressor p53 near the proximal CCAAT box and the fact that the basal expression of annexin A1 in human colon adenocarcinoma cells is driven by p53 at the transcriptional level. Posttranscriptional mechanisms may also play an important role in maintaining constitutive annexin A1 expression. In addition, a p53/NF-Y complex is detected bound to the p53 binding site on its promoter. Butyrate is a natural product of fiber degradation in the colon and a key regulator of colonic epithelium homeostasis. We show that butyrate, a class I and II histone deacetylase inhibitor, induces transcriptional activation of annexin A1 expression correlated with differentiation. The effect of butyrate is mediated through a release of NF-Y from the proximal CCAAT box and an enhancement of p53 binding. The interaction of p53 with the promoter is dependent on p38 MAPK activity either in the absence or in the presence of butyrate. Further, activation of p38 MAPK by this agent is required to increase annexin A1 promoter activity and to increase protein expression.This work was supported by grant BFU2005-02671 from the DGI, Ministerio de Educación y Ciencia (Spain).Peer reviewe

Key role of the N-terminus of chicken annexin A5 in vesicle aggregation

Annexins are calcium-dependent phospholipid-binding proteins involved in calcium signaling and intracellular membrane trafficking among other functions. Vesicle aggregation is a crucial event to make possible the membrane remodeling but this process is energetically unfavorable, and phospholipid membranes do not aggregate and fuse spontaneously. This issue can be circumvented by the presence of different agents such as divalent cations and/or proteins, among them some annexins. Although human annexin A5 lacks the ability to aggregate vesicles, here we demonstrate that its highly similar chicken ortholog induces aggregation of vesicles containing acidic phospholipids even at low protein and/or calcium concentration by establishment of protein dimers. Our experiments show that the ability to aggregate vesicles mainly resides in the N-terminus as truncation of the N-terminus of chicken annexin A5 significantly decreases this process and replacement of the N-terminus of human annexin A5 by that of chicken switches on aggregation; in both cases, there are no changes in the overall protein structure and only minor changes in phospholipid binding. Electrostatic repulsions between negatively charged residues in the concave face of the molecule, mainly in the N-terminus, seem to be responsible for the impairment of dimer formation in human annexin A5. Taking into account that chicken annexin A5 presents a high sequence and structural similarity with mammalian annexins absent in birds, as annexins A3 and A4, some of the physiological functions exerted by these proteins may be carried out by chicken annexin A5, even those that could require calcium-dependent membrane aggregation.Peer reviewe

Deoxycholic and chenodeoxycholic bile acids induce apoptosis via oxidative stress in human colon adenocarcinoma cells

The continuous exposure of the colonic epithelium to high concentrations of bile acids may exert cytotoxic effects and has been related to pathogenesis of colon cancer. A better knowledge of the mechanisms by which bile acids induce toxicity is still required and may be useful for the development of new therapeutic strategies. We have studied the effect of deoxycholic acid (DCA) and chenodeoxycholic acid (CDCA) treatments in BCS-TC2 human colon adenocarcinoma cells. Both bile acids promote cell death, being this effect higher for CDCA. Apoptosis is detected after 30 min–2 h of treatment, as observed by cell detachment, loss of membrane asymmetry, internucleosomal DNA degradation, appearance of mitochondrial transition permeability (MPT), and caspase and Bax activation. At longer treatment times, apoptosis is followed in vitro by secondary necrosis due to impaired mitochondrial activity and ATP depletion. Bile acid-induced apoptosis is a result of oxidative stress with increased ROS generation mainly by activation of plasma membrane enzymes, such as NAD(P)H oxidases and, to a lower extent, PLA2. These effects lead to a loss of mitochondrial potential and release of pro-apoptotic factors to the cytosol, which is confirmed by activation of caspase-9 and -3, but not caspase-8. This initial apoptotic steps promote cleavage of Bcl-2, allowing Bax activation and formation of additional pores in the mitochondrial membrane that amplify the apoptotic signal. Similar content being viewed by othersThis work was supported by grants BFU2005-02671 and BFU2008-04758 from the DGES (Spain).Peer reviewe

In vitro models for the study of the effect of butyrate on human colon adenocarcinoma cells

The effect of butyrate has been analyzed on human colon adenocarcinoma cell lines with different properties regarding tumorigenicity, differentiation and resistance to apoptosis induced by this agent. Butyrate reduces cell proliferation, induces differentiation (according to alkaline phosphatase activity) and apoptosis, being these effects time- and concentration-dependent. The susceptibility to the cytotoxic effects of butyrate depends on the cell line considered and it is not directly related to tumorigenicity or differentiation. We show that 2 mM butyrate treatment of non-tumorigenic BCS-TC2 cells for four days strongly influences the transcriptional activity, causing extensive modification in gene expression patterns (69 up-regulated and 109 down-regulated genes). Some of these genes are involved in the modulation of cell cycle progression, apoptosis and differentiation. We have analyzed the effect of butyrate in spontaneous or induced multicellular spheroids. The more stable spheroids (spontaneous or induced from butyrate-resistant cells) increase the resistance of cells to the effects of butyrate probably due to an impaired accessibility. This in vitro model could be useful to study the resistance of tumors to the effect of natural regulators (i.e. butyrate) as well as to develop and test new therapeutic approaches.This work was supported by Spanish grants BMC2002-01407 and BFU2005-02671 from DGI.Peer reviewe

Circulando hacia la seguridad del paciente: realidad y deseo

Resumen: Objetivo: Valorar diferencias entre necesidad e implementación de prácticas seguras recomendadas para la seguridad del paciente y utilidad del uso de señales de tráfico para promover su implementación. Método: El estudio constó de dos fases: 1) revisión de recomendaciones sobre prácticas seguras de diferentes organizaciones y 2) encuesta a una muestra de oportunidad de profesionales del ámbito asistencial, organizativo y académico de la seguridad del paciente de España y Latinoamérica para evaluar necesidad y la implementación percibida de las prácticas seguras y la utilidad de las señales para tal fin. Resultados: Se recibieron 365 cuestionarios. Todas las prácticas seguras identificadas fueron valoradas como necesarias (media y límite inferior del intervalo de confianza por encima de 3 sobre 5 puntos). Sin embargo, la implementación se valoró como insuficiente en seis de ellas: escritura ilegible, conciliación de medicación, estandarización de comunicación, sistemas de alerta rápida, aplicación de procedimientos por profesionales o equipos entrenados, y cumplimiento de voluntades del paciente al final de la vida. Mejorar cumplimiento de la higiene de manos, aplicación de precauciones de barrera, asegurar la identificación correcta de los pacientes y utilizar listados de verificación fueron las cuatro prácticas en las que más del 75% de los encuestados encuentran mayor grado de consenso sobre la utilidad de las señales de tráfico para mejorar su implementación. Conclusiones: Las diferencias entre necesidad percibida e implementación real de las prácticas seguras consideradas indican áreas de mejora. El lenguaje común de las señales de tráfico es un instrumento sencillo para mejorar su cumplimiento. Abstract: Objective: To evaluate differences between the need and degree of implementation of safe practices recommended for patient safety and to check the usefulness of traffic sign iconicity to promote their implementation. Method: The study was developed in two stages: 1) review of safe practices recommended by different organizations and 2) a survey to assess the perceptions for the need and implementation of them and the usefulness of signs to improve their implementation. The sample consisted of professionals from Spain and Latin America working in healthcare settings and in the academic field related to patient safety. Results: 365 questionnaires were collected. All safe practices included were considered necessary (mean and lower limit of confidence interval over 3 out of 5 points). However, in six of the patient safety practices evaluated the implementation was considered insufficient: illegible handwriting, medication reconciliation, standardization of communication systems, early warning systems, procedures performed or equipment used only by trained people, and compliance with patient preferences at the end of life. Improve compliance of with hand hygiene and barrier precautions to prevent infections, ensure the correct identification of patients and the use of checklists are the four practices in which more than 75% of respondents found a high degree of consensus on the usefulness of traffic sings to broaden their use. Conclusion: The differences between perceived need and actual implementation in some safe practices indicate areas for improvement in patient safety. With this aim, the common language and the iconicity of traffic signs could constitute a simple instrument to improve compliance with safe practices for patient safety. Palabras clave: Seguridad del paciente, Prácticas clínicas seguras, Gestión del riesgo, Yatrogenia, Keywords: Patient safety, Safe clinical practices, Risk management, Iatrogenic diseas

A randomized study comparing parathyroidectomy with cinacalcet for treating hypercalcemia in kidney allograft recipients with hyperparathyroidism

Tertiary hyperparathyroidism is a common cause of hypercalcemia after kidney transplant. We designed this 12-month, prospective, multicenter, open-label, randomized study to evaluate whether subtotal parathyroidectomy is more effective than cinacalcet for controlling hypercalcemia caused by persistent hyperparathyroidism after kidney transplant. Kidney allograft recipients with hypercalcemia and elevated intact parathyroid hormone (iPTH) concentration were eligible if they had received a transplant ≥6 months before the study and had an eGFR>30 ml/min per 1.73 m2. The primary end point was the proportion of patients with normocalcemia at 12 months. Secondary end points were serum iPTH concentration, serum phosphate concentration, bone mineral density, vascular calcification, renal function, patient and graft survival, and economic cost. In total, 30 patients were randomized to receive cinacalcet (n=15) or subtotal parathyroidectomy (n=15). At 12 months, ten of 15 patients in the cinacalcet group and 15 of 15 patients in the parathyroidectomy group (P=0.04) achieved normocalcemia. Normalization of serum phosphate concentration occurred in almost all patients. Subtotal parathyroidectomy induced greater reduction of iPTH and associated with a significant increase in femoral neck bone mineral density; vascular calcification remained unchanged in both groups. The most frequent adverse events were digestive intolerance in the cinacalcet group and hypocalcemia in the parathyroidectomy group. Surgery would be more cost effective than cinacalcet if cinacalcet duration reached 14 months. All patients were alive with a functioning graft at the end of follow-up. In conclusion, subtotal parathyroidectomy was superior to cinacalcet in controlling hypercalcemia in these patients with kidney transplants and persistent hyperparathyroidism