Switching to a rilpivirine/emtricitabine/tenofovir single-tablet regimen in RNA-suppressed patients infected with human immunodeficiency virus 1: Effectiveness, safety and costs at 96 weeks.

OBJECTIVES: This study evaluates the effectiveness, safety and costs of switching to a rilpivirine/emtricitabine/tenofovir disoproxil fumarate (RPV/FTC/TDF) regimen in treatment-experienced HIV-1-infected patients with sustained virological suppression. METHODS: Observational, prospective study. Study population included all treatment-experienced patients with sustained virological suppression who switched to RPV/FTC/TDF during 2013 in a tertiary hospital. Patients were followed until they completed 96 weeks of treatment. The effectiveness end-point was defined as the proportion of patients who maintained virological suppression at week 96 by intention-to-treat analysis (discontinuation=failure). The safety of RPV/FTC/TDF (incidence of adverse events leading to discontinuation and laboratory abnormalities) and adherence to this regimen were evaluated, and the cost of switching was analysed. RESULTS: One-hundred forty-six patients were included. At week 96, 71.9% of patients remained virologically suppressed; 6.8% experienced virological failure. During follow-up, 25.3% of patients discontinued RPV/FTC/TDF (14.4% because of adverse events, mainly renal impairment). Throughout the 96 weeks, there were significant decreases in total cholesterol (TC) (14.0 mg/dL, P<.001), TC/HDL cholesterol ratio (0.4 mg/dL, P=.019) and triglycerides (42.0 mg/dL, P<.001). A slight decrease in glomerular filtration rate was observed (4.3 mL/min/1.73 m2 , P<.001). Switching to RPV/FTC/TDF improved adherence in the subgroup of patients whose previous treatment was based on a twice-daily schedule, although differences did not reach statistical significance. Switching to RPV/FTC/TDF reduced the annual per-patient antiretroviral cost by €1744 (P<.001). CONCLUSIONS: In virologically suppressed patients, the switch to a RPV/FTC/TDF regimen was associated with a mild but maintained improvement in lipid parameters and a significant reduction in costs. However, the relatively high rates of virological failure and treatment discontinuation because of adverse events make this combination a less favourable choice over other regimens currently available.

Level of concordance between two risk-assessment models for predicting venous thromboembolism in medical patients at admission.

OBJECTIVES: To evaluate the level of concordance between the 2007 PRETEMED guidelines and the 2012 American College of Chest Physicians (ACCP) guidelines in medical patients at admission. METHODS: A cross-sectional, observational and descriptive study was designed and included all adult medical patients admitted from an emergency department. Firstly, patients classified as low-moderate risk and high risk according to PRETEMED were compared to those classified by ACCP as low and high risk. Secondly, the same analysis was performed but this time low and moderate-high risk patients according to PRETEMED were compared to ACCP low and high risk patients. The level of concordance was calculated using the kappa concordance index. The study was approved by the Ethics Committee for Clinical Research of the hospital. RESULTS: The analysis was performed with 207 patients; 53.1% were male and the median age was 75.3 years (minimum 18, maximum 100 years old). The most common diagnosis at admission was related to a respiratory disease (37.2%). The level of concordance was 0.59 (95% CI 0.48 to 0.70) when moderate risk patients were grouped with low-risk patients and 0.53 (95% CI 0.42 to 0.65) when moderate risk patients were grouped with high-risk patients. CONCLUSIONS: The level of concordance between both guides is moderate. It would be helpful to confirm whether the level of agreement improves when the patient's condition stabilises after several days of hospitalisation.

[Causes of the emergency department visits in cancer patients: postchemotherapy toxicity]. / Análisis descriptivo de los motivos que originan visitas a urgencias en pacientes oncológicos: toxicidad postquimioterapia.

PURPOSE: to assess the causes of the Emergency Department visits in cancer patients treated with antineoplastics. The secondary objective is to analyse the use of growth stimulating factors in febrile neutropenia. METHODS: a retrospective observational study was conducted during six months of 2012. The adult patients diagnosed with solid tumour that visited the Emergency Department and whose physician was an oncologist, were included. RESULTS: a total of 83 patients fulfilled the inclusion criteria. The causes of visits were: 63% due to the tumour, 31% due to the chemotherapy toxicity and 6% due to other causes. In patients with chemotherapy toxicity, 65% had fever or infection, 50% pain and 42% febrile neutropenia. The treatment and prophylaxis with filgrastim followed the recommendations. CONCLUSIONS: in cancer patients, most of emergencies are due to the tumour. The management of the pain, the fever and the neutropenia is important.

Objetivo: cuantificar y analizar las causas por las que los pacientes oncológicos acuden al Servicio de Urgencias y analizar el uso de factores estimulantes de colonias para la profilaxis o el tratamiento de la neutropenia febril. Método: estudio retrospectivo de seis meses del año 2012. Se incluyeron pacientes adultos con tumor sólido y tratamiento activo atendidos por oncólogos en el Servicio de Urgencias. Resultados: se incluyeron 83 pacientes. Respecto al motivo de consulta: en el 63% es causa tumoral, 31% toxicidad postquimioterapia y 6% otras causas. En los que acuden por toxicidad, el 65% presentaron fiebre o síntomas de infección, el 50% dolor y el 42% neutropenia febril. La profilaxis y el tratamiento de la neutropenia febril con filgrastim siguieron las recomendaciones. Conclusiones: la mayor parte de los episodios oncológicos en Urgencias son debidos al propio proceso tumoral. Algunos problemas importantes son el manejo del dolor, la fiebre y la neutropenia.

Análisis descriptivo de los motivos que originan visitas a urgencias en pacientes oncológicos: toxicidad postquimioterapia / Causes of the emergency department visits in cancer patients: post-chemotherapy toxicity

Objetivo: cuantificar y analizar las causas por las que los pacientes oncológicos acuden al Servicio de Urgencias y analizar el uso de factores estimulantes de colonias para la profilaxis o el tratamiento de la neutropenia febril. Método: estudio retrospectivo de seis meses del año 2012. Se incluyeron pacientes adultos con tumor sólido y tratamiento activo atendidos por oncólogos en el Servicio de Urgencias. Resultados: se incluyeron 83 pacientes. Respecto al motivo de consulta: en el 63% es causa tumoral, 31% toxicidad postquimioterapia y 6% otras causas. En los que acuden por toxicidad, el 65% presentaron fiebre o síntomas de infección, el 50% dolor y el 42% neutropenia febril. La profilaxis y el tratamiento de la neutropenia febril con filgrastim siguieron las recomendaciones. Conclusiones: la mayor parte de los episodios oncológicos en Urgencias son debidos al propio proceso tumoral. Algunos problemas importantes son el manejo del dolor, la fiebre y la neutropenia (AU)

Purpose: to assess the causes of the Emergency Department visits in cancer patients treated with antineoplastics. The secondary objective is to analyse the use of growth stimulating factors in febrile neutropenia. Methods: a retrospective observational study was conducted during six months of 2012. The adult patients diagnosed with solid tumour that visited the Emergency Department and whose physician was an oncologist, were included. Results: a total of 83 patients fulfilled the inclusion criteria. The causes of visits were: 63% due to the tumour, 31% due to the chemotherapy toxicity and 6% due to other causes. In patients with chemotherapy toxicity, 65% had fever or infection, 50% pain and 42% febrile neutropenia. The treatment and prophylaxis with filgrastim followed the recommendations. Conclusions: in cancer patients, most of emergencies are due to the tumour. The management of the pain, the fever and the neutropenia is important (AU)

[Vancomycin intoxication in a patient with inappropriate antidiuretic hormone syndrome and diarrhea]. / Intoxicación por vancomicina en un paciente con síndrome de secreción inadecuada de hormona antidiurética y diarrea.

Vancomycin is an antibiotic used for infections by gram-positive bacteria with a two-compartment pharmacokinetic model. Its monitoring has an established therapeutic range (10-20 mg/L) to prevent nephrotoxicity and ototoxicity due to supratherapeutic levels, and inefficiency and development of resistance by subtherapeutic levels. Nephrotoxicity for vancomycin monotherapy at standard doses according to pathogen and typical regimens (usual dose: 15-20 mg/kg/12 h) is rare and usually reversible. Moreover, monitoring plasma concentrations allows to achieve concentrations within therapeutic range to allow safe and effective drug use. The renal hypoperfusion can cause pre-renal damage, resulting in elevated levels of serum creatinine, resulting in decreased antibiotic elimination and nephrotoxicity. We report a case of unexpected vancomycin nephrotoxicity in a patient with syndrome Inappropriate antidiuretic hormone secretion associated paraneoplastic.

La vancomicina es un antibiotico empleado en infecciones por bacterias gram-positivas con un modelo farmacocinetico bicompartimental. Su monitorizacion ha permitido establecer rangos terapeuticos (10-20 mg/L) que evitan la nefrotoxicidad y la ototoxicidad debidas a niveles supraterapeuticos, asi como la ineficacia y aparicion de resistencias por niveles subterapeuticos. La nefrotoxicidad por vancomicina en monoterapia a dosis habitual segun patogeno y regimenes tipicos (dosis habitual: 15-20 mg/kg/12 h) es poco frecuente y generalmente reversible. Ademas, la monitorizacion de sus concentraciones plasmaticas permite lograr concentraciones en rango terapeutico que facilitan un uso seguro y efectivo del farmaco. La hipoperfusion renal puede producir dano prerrenal, provocando una elevacion de los niveles de creatinina serica, con la consiguiente disminucion de la eliminacion del antibiotico y nefrotoxicidad. Presentamos un caso de nefrotoxicidad no esperada por vancomicina en un paciente con sindrome de secrecion inadecuada de hormona antidiuretica paraneoplasico asociado.

Intoxicación por vancomicina en un paciente con síndrome de secreción inadecuada de hormona antidiurética y diarrea / Vancomycin intoxication in a patient with inappropriate antidiuretic hormone syndrome and diarrhea

La vancomicina es un antibiótico empleado en infecciones por bacterias grampositivas con un modelo farmacocinético bicompartimental. Su monitorización ha permitido establecer rangos terapéuticos (10-20 mg/L) que evitan la nefrotoxicidad y la ototoxicidad debidas a niveles supraterapéuticos, así como la ineficacia y aparición de resistencias por niveles subterapéuticos. La nefrotoxicidad por vancomicina en monoterapia a dosis habitual según patógeno y regímenes típicos (dosis habitual: 15-20 mg/kg/12 h) es poco frecuente y generalmente reversible. Además, la monitorización de sus concentraciones plasmáticas permite lograr concentraciones en rango terapéutico que facilitan un uso seguro y efectivo del fármaco. La hipoperfusión renal puede producir daño prerrenal, provocando una elevación de los niveles de creatinina sérica, con la consiguiente disminución de la eliminación del antibiótico y nefrotoxicidad. Presentamos un caso de nefrotoxicidad no esperada por vancomicina en un paciente con síndrome de secreción inadecuada de hormona antidiurética paraneoplásico asociado (AU)

Vancomycin is an antibiotic used for infections by grampositive bacteria with a two-compartment pharmacokinetic model. Its monitoring has an established therapeutic range (10-20 mg/L) to prevent nephrotoxicity and ototoxicity due to supra-therapeutic levels, and inefficiency and development of resistance by subtherapeutic levels. Nephrotoxicity for vancomycin monotherapy at standard doses according to pathogen and typical regimens (usual dose: 15-20 mg/kg/12 h) is rare and usually reversible. Moreover, monitoring plasma concentrations allows to achieve concentrations within therapeutic range to allow safe and effective drug use. The renal hypoperfusion can cause prerenal damage, resulting in elevated levels of serum creatinine, resulting in decreased antibiotic elimination and nephrotoxicity. We report a case of unexpected vancomycin nephrotoxicity in a patient with syndrome Inappropriate antidiuretic hormone secretion associated paraneoplastic (AU)

Intervenciones farmacéuticas en las prescripciones de pacientes ingresados con insuficiencia renal crónica / Pharmaceutical interventions in prescriptions for patients admitted with chronic renal failure

Antecedentes: La insuficiencia renal crónica (IRC) es una patología que necesita un ajuste posológico de determinados medicamentos. Objetivos: Evaluar las características de las intervenciones farmacoterapéuticas relacionadas con la adecuación de la posología de los medicamentos en los pacientes con IRC que ingresan en un hospital. Métodos: Estudio longitudinal y prospectivo de 10 meses de duración en el que se calculó el filtrado glomerular de los pacientes ingresados desde Urgencias y se seleccionaron los que tenían valores menores de 50 ml/min/1,73 m2. Posteriormente, se realizaron recomendaciones posológicas de los medicamentos que no estaban adaptados a su función renal. Resultados: Se revisó la función renal de 5311 pacientes. Ciento ochenta y uno (3,4 %) tenían un filtrado glomerular menor de 50 ml/min/1,73 m2 y algún medicamento pautado susceptible de ser ajustado. Se registraron 221 intervenciones, siendo la más frecuente la reducción de dosis (65,6 %); un 65,6 % fueron aceptadas por el médico. El grupo de antiinfecciosos tuvo el mayor número de intervenciones (57,5 %). La unidad donde más se intervino fue Medicina Interna (50,2 %).Conclusiones: Los pacientes con IRC ingresados desde Urgencias suponen un objetivo clave en la adecuación de las dosis a la función renal, siendo las recomendaciones farmacéuticas muy valoradas por los médicos por su alta aceptación. La revisión de los medicamentos antiinfecciosos es la que más oportunidades ofrece (AU)

Background: Chronic Renal Failure (CRF) is a disease that requires determined medications dosages to be adjusted. Objectives: To assess the characteristics of pharmaceutical interventions concerning the dose adjustment of these drugs in patients with CRF who are admitted into hospital. Methods: A 10-month prospective and longitudinal study that calculated the glomerular filtration rate of patients who are brought into the emergency department and had values below 50ml/min/1.73m2. Subsequently, dosage recommendations were provided for the drugs that had not been adapted to the patient’s renal function. Results: The renal functions of 5311 patients were reviewed. One-hundred and eighty-one (3.4%) had a glomerular filtration rate below 50ml/min/1.73m2 and were receiving drugs that needed to be adjusted. 221 interventions were recorded. Reductions in dosages were the more frequent results (65.6%); 65.6% of these recommendations were accepted by the doctor. The antimicrobial group had the highest number of interventions (57.5%). Internal Medicine (50.2%) was the unit with the most interventions. Conclusion: CRF patients that are admitted into the emergency department are a key objective concerning dosages in chronic renal failure. Pharmaceutical recommendations are highly esteemed by doctors, given their high acceptance. Revising antimicrobial drugs offers more opportunities (AU)

Pharmaceutical interventions in prescriptions for patients admitted with chronic renal failure.

BACKGROUND: Chronic Renal Failure (CRF) is a disease that requires determined medications dosages to be adjusted. OBJECTIVES: To assess the characteristics of pharmaceutical interventions concerning the dose adjustment of these drugs in patients with CRF who are admitted into hospital. METHODS: A 10-month prospective and longitudinal study that calculated the glomerular filtration rate of patients who are brought into the emergency department and had values below 50ml/min/1.73m2. Subsequently, dosage recommendations were provided for the drugs that had not been adapted to the patient’s renal function. RESULTS: The renal functions of 5311 patients were reviewed. One-hundred and eighty-one (3.4%) had a glomerular filtration rate below 50ml/min/1.73m2 and were receiving drugs that needed to be adjusted. 221 interventions were recorded. Reductions in dosages were the more frequent results (65.6%); 65.6% of these recommendations were accepted by the doctor. The antimicrobial group had the highest number of interventions (57.5%). Internal Medicine (50.2%) was the unit with the most interventions. CONCLUSION: CRF patients that are admitted into the emergency department are a key objective concerning dosages in chronic renal failure. Pharmaceutical recommendations are highly esteemed by doctors, given their high acceptance. Revising antimicrobial drugs offers more opportunities.

[Home parenteral nutrition; satisfaction of patients and their caregivers with nutrition unit and pharmacy service]. / Nutrición parenteral domiciliaria: satisfacción de los pacientes y sus cuidadores con la unidad de nutrición clínica y el servicio de farmacia.

INTRODUCTION: Home Parenteral Nutrition (HPN) is a practice in continually growing by the significant advantages involved for the patient and the healthcare system. Today, in the investigation of health outcomes is essential to assess the patient s opinion. Among the measures focused on patients with HPN, several studies about quality of life have been done, but the degree of satisfaction with this treatment modality has not been evaluated. OBJECTIVE: To evaluate the degree of satisfacion of patients and their caregivers receiving HPN with doctors, pharmacists and nurses in a hospital. MATERIAL AND METHODS: An anonymous survey was distributed, which consisted of 48 closed questions to patients and their caregivers receiving HPN who voluntarily answered. With survey responses a database in SPSS with the following variables was created: personal, sociocultural, clinical and related to HPN data and valoration of health personnel involved (nutrition area of the Pharmacy Service and Nursing and Medical Nutrition Units) and hospital facilities related to HPN. Also a section of open response suggestions was included. RESULTS: 24 surveys were distributed, 12 to patients and 12 to caregivers. Response rate was 91.7% in the case of patients and 58.3% in the caregivers. 63.6% of patients and 42.9% of caregivers were women. Mean age was, respectively, 46.1 years (SD: 13.7) and 47.0 years (SD: 3.6). Most of patients (55.6%) and caregivers (60.0%) had secondary studies and were pensoniers (72.7% and 71.4%, respectively). Underlying diseases of patients were: radiation enteritis (27.3%), intestinal obstruction (18.2%), intestinal carcinomatosis (45.5%) and Chron s disease (9.1%). With respect to items assessing satisfaction with physicians, nurses and pharmacists, in general both patients and caregivers were satisfied. Suggestions made were: greater amplitude of delivery schedule of HPN and inclusion of audiovisual information. CONCLUSIONS: The degree of satisfaction of patients receiving HPN and their caregivers with the care given by doctors, pharmacists and nurses is appropriate, but it s possible to make improvements to optimize the quality of the whole process.

Introducción: La Nutrición Parenteral Domiciliaria (NPD) es una práctica en continuo crecimiento por las importantes ventajas que presenta para el paciente y el sistema sanitario. En la investigación de los resultados en salud resulta hoy en día fundamental evaluar el punto de vista del paciente. Dentro de las medidas centradas en el paciente con NPD se han realizado varios estudios sobre la calidad de vida, pero no se ha evaluado el grado de satisfacción con esta modalidad de tratamiento. Objetivos: Evaluar el grado de satisfacción de los pacientes que reciben NPD y sus cuidadores con los médicos, farmacéuticos y enfermeros de hospital. Métodos: Se repartió una encuesta anónima y que constaba de 48 preguntas cerradas a los pacientes que recibían NPD y a sus cuidadores, los cuales contestaron de forma voluntaria. Con las respuestas recogidas se creó una base de datos en el programa SPSS con las siguientes variables: datos personales, socioculturales, clínicos y relacionados con la NPD y valoración del personal sanitario implicado (área de nutrición del Servicio de Farmacia y Unidades Médica y de Enfermería de Nutrición) y de las instalaciones del hospital relacionadas con la NPD. También se incluyó un apartado de sugerencias con respuesta abierta. Resultados: Se repartieron 24 encuestas, 12 a pacientes y 12 a cuidadores. La tasa de respuesta fue un 91,7% en el caso de los pacientes y un 58,3% en los cuidadores. El 63,6% de los pacientes y el 42,9% de los cuidadores eran mujeres. La media de edad fue, respectivamente, 46,1 años (DE: 13,7) y 47,0 años (DE: 3,6). La mayoría de los pacientes (54,5%) y de los cuidadores (42,9%) tenían estudios secundarios y eran pensionistas (72,7% y 71,4%, respectivamente). Las enfermedades de base de los pacientes fueron: enteritis rádica (27,3%), obstrucción intestinal (18,2%), carcinomatosis intestinal (45,5%) y enfermedad de Crohn (9,1%). Con respecto a los ítems que evaluaban la satisfacción con médicos, enfermeros y farmacéuticos, en general tanto pacientes como cuidadores estuvieron satisfechos. Las sugerencias recogidas fueron: mayor amplitud del horario de entrega de la NPD e inclusión de información audiovisual. Conclusiones: El grado de satisfacción de los pacientes que reciben NPD y sus cuidadores con el servicio dado por médicos, enfermeros y farmacéuticos es adecuado, aunque se pueden introducir mejoras para optimizar la calidad de todo el proceso.

Nutrición Parenteral Domiciliaria; satisfacción de los pacientes y sus cuidadores con la Unidad de Nutrición Clínica y el Servicio de Farmacia / Home parenteral nutrition; satisfaction of patients and their caregivers with nutrition unit and pharmacy service

Introducción: La Nutrición Parenteral Domiciliaria (NPD) es una práctica en continuo crecimiento por las importantes ventajas que presenta para el paciente y el sistema sanitario. En la investigación de los resultados en salud resulta hoy en día fundamental evaluar el punto de vista del paciente. Dentro de las medidas centradas en el paciente con NPD se han realizado varios estudios sobre la calidad de vida, pero no se ha evaluado el grado de satisfacción con esta modalidad de tratamiento. Objetivos: Evaluar el grado de satisfacción de los pacientes que reciben NPD y sus cuidadores con los médicos, farmacéuticos y enfermeros de hospital. Métodos: Se repartió una encuesta anónima y que constaba de 48 preguntas cerradas a los pacientes que recibían NPD y a sus cuidadores, los cuales contestaron de forma voluntaria. Con las respuestas recogidas se creó una base de datos en el programa SPSS con las siguientes variables: datos personales, socioculturales, clínicos y relacionados con la NPD y valoración del personal sanitario implicado (área de nutrición del Servicio de Farmacia y Unidades Médica y de Enfermería de Nutrición) y de las instalaciones del hospital relacionadas con la NPD. También se incluyó un apartado de sugerencias con respuesta abierta. Resultados: Se repartieron 24 encuestas, 12 a pacientes y 12 a cuidadores. La tasa de respuesta fue un 91,7% en el caso de los pacientes y un 58,3% en los cuidadores. El 63,6% de los pacientes y el 42,9% de los cuidadores eran mujeres. La media de edad fue, respectivamente, 46,1 años (DE: 13,7) y 47,0 años (DE: 3,6). La mayoría de los pacientes (54,5%) y de los cuidadores (42,9%) tenían estudios secundarios y eran pensionistas (72,7% y 71,4%, respectivamente). Las enfermedades de base de los pacientes fueron: enteritis rádica (27,3%), obstrucción intestinal (18,2%), carcinomatosis intestinal (45,5%) y enfermedad de Crohn (9,1%). Con respecto a los ítems que evaluaban la satisfacción con médicos, enfermeros y farmacéuticos, en general tanto pacientes como cuidadores estuvieron satisfechos. Las sugerencias recogidas fueron: mayor amplitud del horario de entrega de la NPD e inclusión de información audiovisual. Conclusiones: El grado de satisfacción de los pacientes que reciben NPD y sus cuidadores con el servicio dado por médicos, enfermeros y farmacéuticos es adecuado, aunque se pueden introducir mejoras para optimizar la calidad de todo el proceso (AU)

Introduction: Home Parenteral Nutrition (HPN) is a practice in continually growing by the significant advantages involved for the patient and the healthcare system. Today, in the investigation of health outcomes is essential to assess the patient s opinion. Among the measures focused on patients with HPN, several studies about quality of life have been done, but the degree of satisfaction with this treatment modality has not been evaluated. Objective: To evaluate the degree of satisfacion of patients and their caregivers receiving HPN with doctors, pharmacists and nurses in a hospital. Material and methods: An anonymous survey was distributed, which consisted of 48 closed questions to patients and their caregivers receiving HPN who voluntarily answered. With survey responses a database in SPSS with the following variables was created: personal, sociocultural, clinical and related to HPN data and valoration of health personnel involved (nutrition area of the Pharmacy Service and Nursing and Medical Nutrition Units) and hospital facilities related to HPN. Also a section of open response suggestions was included. Results: 24 surveys were distributed, 12 to patients and 12 to caregivers. Response rate was 91.7% in the case of patients and 58.3% in the caregivers. 63.6% of patients and 42.9% of caregivers were women. Mean age was, respectively, 46.1 years (SD: 13.7) and 47.0 years (SD: 3.6). Most of patients (55.6%) and caregivers (60.0%) had secondary studies and were pensoniers (72.7% and 71.4%, respectively). Underlying diseases of patients were: radiation enteritis (27.3%), intestinal obstruction (18.2%), intestinal carcinomatosis (45.5%) and Chron s disease (9.1%). With respect to items assessing satisfaction with physicians, nurses and pharmacists, in general both patients and caregivers were satisfied. Suggestions made were: greater amplitude of delivery schedule of HPN and inclusion of audiovisual information. Conclusions: The degree of satisfaction of patients receiving HPN and their caregivers with the care given by doctors, pharmacists and nurses is appropriate, but it s possible to make improvements to optimize the quality of the whole process (AU)