Análisis de la cultura de seguridad en una Unidad de Cardiología gestionada por procesos / Analysis of the safety culture in a Cardiology Unit managed by processes

Resumen La cultura sobre seguridad se perfila como uno de los requisitos para evitar la aparición de efectos adversos, sin embargo, no se ha estudiado en el ámbito de la cardiología. Objetivo: es evaluar la cultura de seguridad en una unidad de cardiología que tiene implantado y certificado un sistema integrado de gestión de calidad y riesgos para la seguridad del paciente. Método: Se realizó un estudio observacional trasversal en 2 años consecutivos utilizando la encuesta Hospital Survey on Patient Safety Culture de la «Agency for Healthcare Research and Quality¼ en su versión española (42 ítems agrupados en 12 dimensiones) sobre todo el personal. Se comparó el porcentaje de respuestas positivas de cada dimensión en 2014 y 2015, así como con los datos a nivel nacional y en EE. UU., siguiendo las recomendaciones establecidas. Resultados: La valoración global, sobre un máximo de 5, fue de 4.5 en 2014 y de 4.7 en 2015. Identificamos 7 dimensiones como fortaleza. Las peor valoradas fueron: Dotación de personal, Apoyo de la gerencia y Trabajo en equipo entre unidades. La comparación mostró superioridad en todas las dimensiones a nivel nacional, y en 8 respecto a los datos del registro americano. Conclusiones: La cultura de seguridad en una unidad de cardiología con un sistema integrado de gestión de calidad y riesgos y seguridad del paciente es elevada, superior a la nacional en todas sus dimensiones y en la mayoría de ellas respecto al registro de EE. UU.

Abstract Safety culture is one of the requirements for preventing the occurrence of adverse effects. However, this has not been studied in the field of cardiology. The aim of this study is to evaluate the safety culture in a cardiology unit that has implemented and certified an integrated quality and risk management system for patient safety. Methods: A cross-sectional observational study was conducted in 2 consecutive years, with all staff completing the Spanish version of the questionnaire, ''Hospital Survey on Patient Safety Culture'' of the ''Agency for Healthcare Research and Quality'', with 42 items grouped into 12 dimensions. The percentage of positive responses in each dimension in 2014 and 2015 were compared, as well as national data and United States data, following the established rules. Results: The overall assessment out of a possible 5, was 4.5 in 2014 and 4.7 in 2015. Seven dimensions were identified as strengths. The worst rated were: staffing, management support and teamwork between units. The comparison showed superiority in all dimensions compared to national data, and in 8 of them compared to American data. Conclusions: The safety culture in a Cardiology Unit with an integrated quality and risk management patient safety system is high, and higher than nationally in all its dimensions and in most of them compared to the United States.

[Analysis of the safety culture in a Cardiology Unit managed by processes]. / Análisis de la cultura de seguridad en una Unidad de Cardiología gestionada por procesos.

Safety culture is one of the requirements for preventing the occurrence of adverse effects. However, this has not been studied in the field of cardiology. The aim of this study is to evaluate the safety culture in a cardiology unit that has implemented and certified an integrated quality and risk management system for patient safety. METHODS: A cross-sectional observational study was conducted in 2 consecutive years, with all staff completing the Spanish version of the questionnaire, "Hospital Survey on Patient Safety Culture" of the "Agency for Healthcare Research and Quality", with 42 items grouped into 12 dimensions. The percentage of positive responses in each dimension in 2014 and 2015 were compared, as well as national data and United States data, following the established rules. RESULTS: The overall assessment out of a possible 5, was 4.5 in 2014 and 4.7 in 2015. Seven dimensions were identified as strengths. The worst rated were: staffing, management support and teamwork between units. The comparison showed superiority in all dimensions compared to national data, and in 8 of them compared to American data. CONCLUSIONS: The safety culture in a Cardiology Unit with an integrated quality and risk management patient safety system is high, and higher than nationally in all its dimensions and in most of them compared to the United States.

Estrategias diuréticas en insuficiencia cardiaca aguda con disfunción renal: terapia convencional frente a guiada por el antígeno carbohidrato 125. Diseño de ensayo clínico / Diuretic strategies in acute heart failure and renal dysfunction: conventional vs carbohydrate antigen 125-guided strategy. Clinical trial design

Introducción y objetivos: El tratamiento óptimo de pacientes con insuficiencia cardiaca aguda (ICA) y síndrome cardiorrenal tipo 1 (SCR-1) no está bien definido. La hipoperfusión arterial y la congestión venosa tienen un papel fundamental en la fisiopatología del SCR-1. El antígeno carbohidrato 125 (CA125) ha emergido como marcador indirecto de sobrecarga de volumen en la ICA. El objetivo de este estudio es evaluar la utilidad del CA125 para el ajuste del tratamiento diurético de pacientes con SCR-1. Métodos: Ensayo clínico multicéntrico, abierto y paralelo, que incluye a pacientes con ICA y creatinina ≥ 1,4 mg/dl al ingreso, aleatorizados a: a) estrategia convencional: titulación basada en la evaluación clínica y bioquímica habitual, o b) estrategia basada en CA125: dosis altas de diuréticos si CA125 > 35 U/ml y bajas en caso contrario. El objetivo principal es el cambio en la función renal a las 24 y las 72 h tras el comienzo del tratamiento. Como objetivos secundarios: a) cambios clínicos y bioquímicos a las 24 y las 72 h, y b) cambios en la función renal y eventos clínicos mayores a 30 días. Resultados: Los resultados de este estudio aportarán datos relevantes sobre la utilidad del CA125 para guiar el tratamiento diurético en el SCR-1. Además, permitirá ampliar el conocimiento de la fisiopatología de esta compleja entidad clínica. Conclusiones: La hipótesis del presente estudio es que las concentraciones de CA125 aumentadas pueden identificar a una población de pacientes con SCR-1 para quienes una estrategia diurética más intensa puede ser beneficiosa. Por el contrario, las concentraciones bajas de esta glucoproteína seleccionarían a los pacientes para los que serían perjudiciales las dosis altas de diuréticos (AU)

Introduction and objectives: The optimal treatment of patients with acute heart failure (AHF) and cardiorenal syndrome type 1 (CRS-1) is far from being well-defined. Arterial hypoperfusion in concert with venous congestion plays a crucial role in the pathophysiology of CRS-I. Plasma carbohydrate antigen 125 (CA125) has emerged as a surrogate of fluid overload in AHF. The aim of this study was to evaluate the clinical usefulness of CA125 for tailoring the intensity of diuretic therapy in patients with CRS-1. Methods: Multicenter, open-label, parallel clinical trial, in which patients with AHF and serum creatinine ≥ 1.4 mg/dL on admission will be randomized to: a) standard diuretic strategy: titration-based on conventional clinical and biochemical evaluation, or b) diuretic strategy based on CA125: high dose if CA125 > 35 U/mL, and low doses otherwise. The main endpoint will be renal function changes at 24 and 72 hours after therapy initiation. Secondary endpoints will include: a) clinical and biochemical changes at 24 and 72 hours, and b) renal function changes and major clinical events at 30 days. Results: The results of this study will add important knowledge on the usefulness of CA125 for guiding diuretic treatment in CRS-1. In addition, it will pave the way toward a better knowledge of the pathophysiology of this challenging situation. Conclusions: We hypothesize that higher levels of CA125 will identify a patient population with CRS-1 who could benefit from the use of a more intense diuretic strategy. Conversely, low levels of this glycoprotein could select those patients who would be harmed by high diuretic doses (AU)

Diuretic Strategies in Acute Heart Failure and Renal Dysfunction: Conventional vs Carbohydrate Antigen 125-guided Strategy. Clinical Trial Design.

INTRODUCTION AND OBJECTIVES: The optimal treatment of patients with acute heart failure (AHF) and cardiorenal syndrome type 1 (CRS-1) is far from being well-defined. Arterial hypoperfusion in concert with venous congestion plays a crucial role in the pathophysiology of CRS-I. Plasma carbohydrate antigen 125 (CA125) has emerged as a surrogate of fluid overload in AHF. The aim of this study was to evaluate the clinical usefulness of CA125 for tailoring the intensity of diuretic therapy in patients with CRS-1. METHODS: Multicenter, open-label, parallel clinical trial, in which patients with AHF and serum creatinine ≥ 1.4mg/dL on admission will be randomized to: a) standard diuretic strategy: titration-based on conventional clinical and biochemical evaluation, or b) diuretic strategy based on CA125: high dose if CA125 > 35 U/mL, and low doses otherwise. The main endpoint will be renal function changes at 24 and 72hours after therapy initiation. Secondary endpoints will include: a) clinical and biochemical changes at 24 and 72hours, and b) renal function changes and major clinical events at 30 days. RESULTS: The results of this study will add important knowledge on the usefulness of CA125 for guiding diuretic treatment in CRS-1. In addition, it will pave the way toward a better knowledge of the pathophysiology of this challenging situation. CONCLUSIONS: We hypothesize that higher levels of CA125 will identify a patient population with CRS-1 who could benefit from the use of a more intense diuretic strategy. Conversely, low levels of this glycoprotein could select those patients who would be harmed by high diuretic doses.

Drug-eluting stents for off-label indications in real clinical world: evidence based or 'intuition' based clinical practice?

BACKGROUND: The use of drug-eluting stents (DES) is an example of the disparity between recommendations given by regulatory agencies and the real clinical world. Such disparity might lead cardiologists to adopt different routines in the use of DES. We aimed to assess variability of off-label DES use between hospitals and to what extent it can be explained by differences in patient or hospital characteristics. METHODS: Characteristics of consecutive patients receiving DES in 29 hospitals were recorded. Individual and hospital determinants of receiving DES for off-label indications were assessed by multilevel logistic regression. RESULTS: 1903 patients were recruited and 1188 (62.4%) received DES for off-label indications. Individual variables associated with off-label use were age (OR 1.01 (1-1.02)), previous percutaneous (OR 2.24 (1.68-2.97)) or surgical (2.41 (1.52-3.84)) revascularization, repeated procedure at the same admission (OR 4.66 (2.7-8.05)), receiving two (OR 4.17 (3.24-5.37)) or three or more DES (OR 14.12 (9.08-21.96)) vs one. Adjusting for individual variables, the Odds of receiving DES for off-label indication was higher in public funding hospitals with surgery availability vs private hospitals: 1.49 (0.86-2.6), and in public hospitals without surgery vs public with surgery availability: OR 1.76 (1.02-3.03). Interhospital variability reminded significant after adjustment for individual and contextual variables. CONCLUSION: Off-label DES use is highly variable between centers. Although this variability is partially determined by hospital type of funding and cardiac surgery availability, the substantial interhospital variability after multilevel adjustment suggests heterogeneity in the process of care.

Lesões supurativas intracranianas / Intracranial suppurative lesions

Este artigo apresenta revisão sobre as lesões supurativas intracranianas. A maioria dessas afecções são resultado de infecções, traumas ou cirurgias. Os pacientes geralmente manifestam um largo espectro de sintomas inespecíficos, o que exige alto grau de suspeição. Exames de imagem são indispensáveis para confirmação do diagnóstico. O tratamento se baseia em antibioticoterapia intensiva e abordagem neurocirúrgica. Diagnóstico precoce e tratamento agressivo são essenciais para um bom prognóstico.

Presents review of Intracranial Suppurative Lesions. These affections are consequence of infections, trauma or surgery. Patients usually manifest a large unspecific spectrum of clinical symptoms, so, a high level of suspicion is required. Imaging exams are indispensable to confirm the diagnosis. The treatment is based on intensive antibiotic therapy and surgical evacuation. Early diagnosis with aggressive medical and surgical management are essential to improved outcome.

Complicações intracranianas de rinossinusite / Intracranials complications of rhinosinusitis

Apresenta-se caso de abscesso epidural intracraniano associado a um empiema subdural como complicações de rinossinusite. O diagnóstico foi feito pela clínica em conjunto com a tomografia computadorizada. O paciente foi tratado com antibioticoterapia tríplice e intervenção cirúrgica para drenagem de empiema, evoluindo para a cura.

Report a case of intracranial epidural abscess associated with subdural empyema as a complication of a rhinosinusitis. The diagnosis was made by the clinical course and computerized tomography. The patient was treated with antibiotic therapy of wide spectrum and surgical treatment to drain the empyema, going to cure.

Prognostic value of glomerular filtration rate 1 year after heart transplantation.

INTRODUCTION AND OBJECTIVES: The development of renal failure is one of the most important problems after heart transplantation (HT), but the wide range of definitions means that estimates of its prevalence vary considerably. Furthermore, its impact on mortality has not been adequately studied. The objective was to investigate the relationship between the glomerular filtration rate (GFR) 1 year after transplantation and mortality during follow-up. METHODS: The GFR was determined in 316 patients still living 1 year after transplantation using the abbreviated Modification of Diet in Renal Disease Study formula. Patients were divided into three groups according to GFR (i.e. <30, 30-59 and > or =60 mL/min per 1.73 m2) and pretransplant variables and rejection and infection rates within the first year were analyzed. The association between GFR at 1 year and mortality during follow-up was evaluated and reasons for the association were examined. RESULTS: There was no difference in the number of rejections or infections in the first year between the three groups. During a mean follow-up period of 6.3 years, 74% of patients with a GFR <30 mL/min per 1.73 m2 died, compared with 24% and 30% of those with a GFR > or =60 and 30-59 mL/min per 1.73 m2, respectively. Survival analysis (i.e. Cox regression analysis) demonstrated a significant difference between patients with a GFR <30 mL/min per 1.73 m2 and other patients (P< .001). A very low GFR at 1 year was the only independent predictor that remained statistically significant on multivariate analysis (hazard ratio =2.87; 95% confidence interval, 1.52-5.41). CONCLUSIONS: Severe renal dysfunction at 1 year was an independent predictor of long-term all-cause mortality in heart transplant patients.

Valor pronóstico de la tasa de filtración glomerular al año del trasplante cardiaco / Prognostic value of glomerular filtration rate 1 year after heart transplantation

Introducción y objetivos. Uno de los problemas más relevantes tras el trasplante cardiaco es el desarrollo de insuficiencia renal. La heterogeneidad en su definición hace que la estimación de su prevalencia sea variable. Por otro lado, su impacto en la mortalidad no ha sido suficientemente estudiado. El objetivo fue evaluar la relación entre la tasa de filtración glomerular al año (TFG) y la mortalidad en el seguimiento. Métodos. Se analizó la TFG de 316 pacientes vivos al año del trasplante mediante la fórmula abreviada Modification of Diet in Renal Disease Study. Se clasificaron en tres grupos según su TFG ( < 30, 30-59 y ≥ 60 ml/ min/1,73 m2, respectivamente) y se analizaron variables antes del trasplante, tasa de rechazo e infección durante el primer año. Se evaluó la relación entre la TFG al año y la mortalidad en el seguimiento y se revisaron sus causas. Resultados. No hubo diferencias en el número de rechazos ni infecciones durante el primer año en los tres grupos. En el seguimiento medio (6,3 años) falleció el 74% de los pacientes con TFG < 30, frente al 24% y al 30% de aquellos con TFG ≥ 60 y 30-59, respectivamente. El análisis de supervivencia (regresión de Cox) mostró diferencias estadísticamente significativas entre aquellos con TFG < 30 y el resto (p < 0,001). La TFG gravemente disminuida al año se mantuvo como el único predictor independiente en el análisis multivariable (hazard ratio = 2,87; intervalo de confianza del 95%, 1,52-5,41). Conclusiones. La disfunción grave de la función renal al año es un predictor independiente de mortalidad por todas las causas a largo plazo en el paciente con trasplante cardiaco (AU)

Introduction and objectives. The development of renal failure is one of the most important problems after heart transplantation (HT), but the wide range of definitions means that estimates of its prevalence vary considerably. Furthermore, its impact on mortality has not been adequately studied. The objective was to investigate the relationship between the glomerular filtration rate (GFR) 1 year after transplantation and mortality during follow-up. Methods. The GFR was determined in 316 patients still living 1 year after transplantation using the abbreviated Modification of Diet in Renal Disease Study formula. Patients were divided into three groups according to GFR (i.e. <30 30-59 and 8805 60 ml min per 1 73 m2 pretransplant variables rejection infection rates within the first year were analyzed association between gfr at mortality during follow-up was evaluated reasons for examined results there no difference in number of rejections or infections three groups a mean period 6 3 years 74 patients with <30 ml min per 1 73 m2 died compared with 24 and 30 of those a gfr 8805 60 30-59 respectively survival analysis i e cox regression demonstrated significant difference between patients <30 ml min per 1 73 m2 and other patients p <.001). A very low GFR at 1 year was the only independent predictor that remained statistically significant on multivariate analysis (hazard ratio =2.87; 95% confidence interval, 1.52-5.41). Conclusions. Severe renal dysfunction at 1 year was an independent predictor of long-term all-cause mortality in heart transplant patients (AU)

Predictors of renal dysfunction at 1 year in heart transplant patients.

BACKGROUND: Renal dysfunction (RD) is one of the most significant long-term complications of heart transplantation (HT). Although RD is generally attributed to a direct effect of calcineurin inhibitors, it is more probable that multiple factors contribute to its development. The aim of this study was to search for predictor variables of RD at 1 year after HT. METHODS: Three hundred sixteen consecutive HT patients were evaluated. The relationship between RD at 1 year (glomerular filtration rate <60 mL/min/1.73 m2), and pretransplant and 1-year follow-up variables was analyzed. RESULTS: At 1 year following HT, 181 patients (57%) had a glomerular filtration rate of <60 mL/min/1.73 m2. On multivariate analysis, pretransplant serum creatinine values (odds ratio [OR] 5.106, 95% confidence interval [CI]: 2.35-11.09, P=0.0001) and cytomegalovirus (CMV) infection (OR 2.04, 95% CI: 1.08-3.83, P=0.027) were significant predictors of RD, and diabetes mellitus was almost significant (OR 1.65, 95% CI: 0.98-2.76, P=0.055). Variables protective against RD were induction therapy with interleukin-2 receptor antagonists versus muromonab-CD3 (OR 0.389, 95% CI: 0.24-0.61, P=0.0001), maintenance treatment with mycophenolate mofetil versus azathioprine (OR 0.42, 95% CI: 0.26-0.68, P=0.0001), and CMV antiviral prophylaxis (OR 0.38, 95% CI: 0.17-0.68, P=0.021). CONCLUSIONS: Fifty-seven percent of HT patients had RD at 1 year posttransplant. RD was associated with pretransplant serum creatinine values, CMV infection, and diabetes mellitus. Induction with interleukin-2 receptor antagonists, treatment with mycophenolate mofetil, and antiviral prophylaxis for CMV infection all helped maintain renal function in this cohort of HT patients.

Technical reliability and clinical safety of a remote monitoring system for antiarrhythmic cardiac devices.

INTRODUCTION AND OBJECTIVES: In recent years, physicians have experienced a huge increase in workload associated with cardiac devices. Remote monitoring enables these devices to be monitored at a distance and could reduce the number of hospital visits. The aim of this study was to assess the technical reliability and clinical safety of the Home MonitoringTM remote monitoring system (Biotronik GmbH, Germany). METHODS: The study included 162 patients: 115 with pacemakers, 44 with implantable cardioverter-defibrillators (ICDs) and three with ICDs incorporating cardiac resynchronization therapy (CRT). Patients were followed up for a mean of 303+/-244 days. We compared the survival time free of event alerts in patients with pacemakers and in those with ICDs. The remote monitoring system's reliability was evaluated by comparing the data it transmitted with clinical observations made immediately afterwards. RESULTS: The mean percentage of days monitored was 88.2%. The incidence of event alerts was higher in pacemaker than ICD patients (45% vs. 34%; P=.01). Event alerts preceded the following hospital visit by 76+/-47 days. In the ICD group, the data sent by the monitoring system were judged as true-positives in 42% of cases, as true-negatives in 57% and as false-positives in 1%. No false-negative was observed. In the ICD group, the remote monitoring system had a sensitivity of 100% and a specificity of 97% (positive predictive value 96%, negative predictive value 100%). CONCLUSIONS: Remote monitoring was a reliable and safe method for following up patients with cardiac devices. Its routine use could enable the early detection of device malfunctions or arrhythmic events.

Fiabilidad técnica y seguridad clínica de un sistema de monitorización remota de dispositivos cardiacos antiarrítmicos / Technical reliability and clinical safety of a remote monitoring system for antiarrhythmic cardiac devices

Introducción y objetivos. En los últimos años se ha producido una sobrecarga de trabajo en las consultas de dispositivos cardiacos. La monitorización remota permite su evaluación a distancia y podría reducir el número de visitas hospitalarias. Los objetivos del estudio han sido evaluar la fiabilidad técnica y la seguridad clínica del sistema Home MonitoringTM (HM, Biotronik GmbH, Alemania). Métodos. Hemos evaluado a 162 pacientes portadores de marcapasos (115), DAI (44) y DAI-TRC (3), durante un seguimiento medio de 303 ± 244 días. Se comparó la supervivencia libre de sucesos de alarma entre los pacientes portadores de marcapasos y DAI. La fiabilidad del HM fue analizada comprobando los datos transmitidos con la evaluación clínica presencial inmediatamente posterior. Resultados. El porcentaje medio de días monitorizados fue el 88,2%. La incidencia de sucesos de alerta fue mayor en el grupo de marcapasos que en el de DAI (el 45 frente al 34%; p = 0,01). Los sucesos de alerta precedieron a la siguiente visita programada en 76 ± 47 días. En el grupo de DAI los datos transmitidos por el HM fueron juzgados como verdaderos positivos en el 42%, como verdaderos negativos en el 57% y como falso positivo en un 1% de los casos. No observamos ningún falso negativo. El HM mostró en el grupo de DAI sensibilidad y especificidad del 100 y el 97% (VPP, 96%; VPN, 100%). Conclusiones. El HM es una herramienta fiable y segura para el seguimiento de los pacientes con un dispositivo cardiaco. Su utilización rutinaria permitiría detectar precozmente anomalías del funcionamiento del dispositivo o sucesos arrítmicos (AU)

Introduction and objectives. In recent years, physicians have experienced a huge increase in workload associated with cardiac devices. Remote monitoring enables these devices to be monitored at a distance and could reduce the number of hospital visits. The aim of this study was to assess the technical reliability and clinical safety of the Home MonitoringTM remote monitoring system (Biotronik GmbH, Germany). Methods. The study included 162 patients: 115 with pacemakers, 44 with implantable cardioverterdefibrillators (ICDs) and 3 with ICDs incorporating cardiac resynchronization therapy (CRT). Patients were followed up for a mean of 303 (244) days. We compared the survival time free of event alerts in patients with pacemakers and in those with ICDs. The remote monitoring system’s reliability was evaluated by comparing the data it transmitted with clinical observations made immediately afterwards. Results. The mean percentage of days monitored was 88.2%. The incidence of event alerts was higher in pacemaker than ICD patients (45% vs 34%; P=.01). Event alerts preceded the following hospital visit by 76 (47) days. In the ICD group, the data sent by the monitoring system were judged as true-positives in 42% of cases, as true-negatives in 57% and as false-positives in 1%. No false-negative was observed. In the ICD group, the remote monitoring system had a sensitivity of 100% and a specificity of 97% (positive predictive value 96%, negative predictive value 100%). Conclusions. Remote monitoring was a reliable and safe method for following up patients with cardiac devices. Its routine use could enable the early detection of device malfunctions or arrhythmic events (AU)

Influence of immunosuppressive regimens on short-term morbidity and mortality in heart transplantation.

BACKGROUND: The goal of immunosuppressive therapy in heart transplantation is to maximize safety and efficacy while minimizing morbidity and mortality. We now have numerous drug combinations, but few have been compared with each other. AIM: To compare various immunosuppressive regimens assessing morbidity and mortality at one yr. METHODS: A total of 351 patients transplanted between 1989 and 2005 were included and grouped by immunosuppressive regimen into group 1 (n = 52): Muronomab (OKT3) 10 d, cyclosporine (CSA), azathioprine (AZA), steroids; group 2 (n = 193): OKT3 seven d, CSA, AZA, steroids; group 3 (n = 22): OKT3 seven d, CSA, mycophenolate mofetil (MMF), steroids; and group 4 (n = 84): interleukin-2 antagonists (IL-2), CSA, MMF, steroids. RESULTS: The incidence of acute graft failure and treated rejection was similar between groups (17% and 78% respectively). We found a statistically significant difference in the incidence of infections (p < 0.001), renal dysfunction (p = 0.011) and in diabetes mellitus (p = 0.023). There were no differences in survival at 30 d (97%), but differences were found at one yr (p = 0.011). The multivariate analysis showed a strong association between mortality and infection (p = 0.001) and between survival and the group 4 regimen (p < 0.001). CONCLUSION: There are differences in survival at one yr of heart transplant patients depending on the immunosuppressive regimen used. The best combination was induction with IL-2 antagonists, followed by CSA, MMF and steroids.