[Analysis of the evolution of outpatient pharmaceutical care in hospital pharmacy services in Spain after the implementation and development of the MAPEX initiative]. / Analisis de la evolución de la atención farmacéutica al paciente externo en los servicios de farmacia hospitalaria en España tras la puesta en marcha y desarrollo de la iniciativa MAPEX.

INTRODUCTION AND OBJECTIVE: In 2015, the Spanish Society of Hospital Pharmacy (SEFH) launched the Strategic Map for Outpatient Pharmaceutical Care (MAPEX), with the purpose of adapting the activity offered in Hospital Pharmacy outpatient clinics to the new healthcare context. The aim of the present study was to analyse the evolution of outpatient pharmaceutical care in Hospital Pharmacy Services in Spain in the period 2016-2021 after the implementation and development of the MAPEX initiative. MATERIAL AND METHOD: The implementation and development of the project was carried out by a group of experts from SEFH and consisted of five phases: creation of the structure, consensus conference, situation analysis, development of strategic initiatives and evolutionary analysis. To analyse the evolutionary development, a specific 43-item questionnaire was developed that addressed aspects related to structure, context, integration, processes, outcomes and research and was answered in 2016 and 2021 (in the latter case by adding 3 additional questions). RESULTS: 141 hospitals participated in the status survey in 2016 and 138 in 2021. Significant differences were found in all dimensions analysed. None of the aspects assessed suffered a setback in this period. The most highly rated aspects at the general level were the improvement of the care model (65.0%) and at the local level, the incorporation of non-face-to-face pharmaceutical care (42.8%). Further progress in the coming years in the expansion and practical application of the methodology proposed in the project was considered a priority. CONCLUSIONS: The implementation and development of the MAPEX initiative has had a positive impact in terms of quality of care for outpatient pharmaceutical care in Hospital Pharmacy services in Spain.

[Development of the Q-PEX standard for quality certification of pharmaceutical care for outpatients of Pharmacy services]. / Desarrollo de la norma Q-PEX de certificación de calidad de la atención farmacéutica a pacientes externos de los servicios de Farmacia.

OBJECTIVE: The objective of this study is to describe the process of creation and development of the quality certification standard for pharmaceutical care for outpatients of the Pharmacy services. METHOD: The methodology was carried out by a group of experts from the Spanish Society of Hospital Pharmacy (SEFH) and consisted of three phases: situation analysis, development of the standard and definition of the self-assessment tool and, finally, piloting in several hospitals, determining its feasibility, carrying out a new revision and readaptation. RESULTS: A standard was defined with 118 items distributed in ten areas. Of these, 19 were considered compulsory, 36 basic, 40 medium and 23 advanced. Three levels of certification were established, as well as the definition and percentages of compliance with the requirements. The certification process was divided into two stages, the one of previous preparation and the audit itself, where the initial certification would be covered, with four phases - first three led by the certification Company, and the last one by SEFH and the subsequent follow-up and re-certification audits. Two hospitals piloted the process carried out the piloting of the whole process, both obtaining a basic level after the adoption of measures and corrective actions, after which the final definition of the external evaluation of the standard and the name of the standard was agreed upon «Q-PEX¼, as well as, the registration of the intellectual property of said standard in July-2020. CONCLUSIONS: The standard for certification of the quality of pharmaceutical care for outpatients developed aims to help the continuous advancement of Hospital Pharmacy services.

[Clinical guidelines for infantile-onset Pompe disease]. / Guia clinica de la enfermedad de Pompe infantil.

Infantile-onset Pompe disease has a fatal prognosis in the short term unless it is diagnosed at an early stage and enzyme replacement therapy is not started as soon as possible. A group of specialists from different disciplines involved in this disease have reviewed the current scientific evidence and have drawn up an agreed series of recommendations on the diagnosis, treatment and follow-up of patients. We recommend establishing enzyme treatment in any patient with symptomatic Pompe disease with onset within the first year of life, with a clinical and enzymatic diagnosis, and once the CRIM (cross-reactive immunological material) status is known.

TITLE: Guia clinica de la enfermedad de Pompe infantil.La enfermedad de Pompe infantil tiene un pronostico fatal a corto plazo si no se diagnostica precozmente ni se inicia un tratamiento enzimatico sustitutivo lo antes posible. Un grupo de especialistas de las diferentes disciplinas involucradas en esta enfermedad ha revisado la evidencia cientifica actual y ha elaborado por consenso una serie de recomendaciones para el diagnostico, el tratamiento y el seguimiento de los pacientes. Se recomienda instaurar tratamiento enzimatico en todo paciente con enfermedad de Pompe sintomatica de comienzo en el primer año de vida, con diagnostico clinico y enzimatico, y una vez conocido el estado CRIM (material inmunologico con reactividad cruzada).

Safe intravenous administration in pediatrics: A 5-year Pediatric Intensive Care Unit experience with smart pumps. / Administración segura de medicamentos intravenosos en pediatría: 5 años de experiencia de una Unidad de Cuidados Intensivos Pediátricos con bombas de infusión inteligentes.

OBJECTIVES: To estimate the impact of smart pump implementation in a pediatric intensive care unit in terms of number and type of administration errors intercepted. DESIGN: Observational, prospective study carried out from January 2010 to March 2015 with syringe and great volumen infusion pumps available in the hospital. SETTING: A tertiary level hospital pediatric intensive care unit. PARTICIPANTS: Infusions delivered with infusion pumps in all pediatric intensive care unit patients. INTERVENTIONS: Design of a drug library with safety limits for all intravenous drugs prescribed. MAIN VARIABLES: Users' compliance with drug library as well as number and type of errors prevented were analyzed. RESULTS: Two hundred and eighty-three errors were intercepted during 62 months of study. A high risk drug was involved in 58% of prevented errors, such as adrenergic agonists and antagonists, sedatives, analgesics, neuromuscular blockers, opioids, potassium and insulin. Users' average compliance with the safety software was 84%. CONCLUSIONS: Smart pumps implementation has proven effective in intercepting high risk drugs programming errors. These results might be exportable to other critical care units, involving pediatric or adult patients. Interdisciplinary colaboration is key to succeed in this process.

[Systemic cytomegalovirus infection: changes in serum calcium and magnesium levels with foscarnet treatment]. / Infección sistémica por citomegalovirus: influencia del tratamiento con foscarnet en los niveles plasmáticos de calcio y magnesio.

Cytomegalovirus infection is common in cardiac transplant patients. Foscarnet is used, with limited evidence, as second-line treatment after ganciclovir failure in these patients. We describe the case of a paediatric cardiac transplant patient who developed electrolyte disturbances during foscarnet treatment for cytomegalovirus infection. The infection resolved after 6 weeks of treatment. Low ionized calcium and magnesium levels were observed during the drug infusion, which were treated with supplements. The serum levels reverted to normal after drug withdrawal.

The treatment for primary immune thrombocytopenia with romiplostim in adult and paediatric patients: use experience at a Spanish university hospital.

WHAT IS KNOWN AND OBJECTIVE: Primary immune thrombocytopenia (ITP) is characterized by accelerated platelet destruction, as well as suboptimal platelet production. Thrombopoietin (TPO) receptor agonists bind to and activate human TPO receptor, and have been shown to increase platelet counts. In this study, we assessed the effectiveness and safety of long-term administration of TPO agonist romiplostim in adult and paediatric patients. METHODS: This is a retrospective observational study that included every ITP patient (adults and children) who received romiplostim since its inclusion in our institutional formulary. Data on patients' demographics, romiplostim doses, platelet counts, use of rescue medication and concurrent therapies were collected. Outcomes for effectiveness evaluation were proportion of patients who achieved a platelet response (platelet count >50 × 10(9) per litre and double the platelet count at baseline on any scheduled visit, excluding counts obtained within 8 weeks after receipt of rescue medications), proportion of patients who achieved a durable response (platelet responses during 6 or more weeks of the last 8 weeks of treatment), proportion of patients needing rescue medication, proportion of patients able to stop or reduce concurrent treatment and mean number of weekly platelet responses. Safety was assessed on the basis of the incidence of adverse events documented on the patients' medical records. RESULTS AND DISCUSSION: This study enrolled ten adults and four paediatric patients. None of the paediatric patients and one adult patient had been splenectomized (contraindicated in the other adults). In the adult population, eight achieved a response at least once during treatment, and 1 achieved a durable response. Four patients needed rescue medication (mostly intravenous immunoglobulins). Three patients were able to stop concurrent ITP therapies, and the mean number of weekly platelet responses was 6. All four paediatric patients achieved a response at least once during treatment, and three achieved durable responses. Three patients needed rescue medication. The only patient who was receiving concurrent ITP medication was able to stop it, and the mean number of weekly platelet responses was 25. No serious adverse events were registered during treatment in either population. WHAT IS NEW AND CONCLUSION: The effectiveness of romiplostim was variable with few adult patients achieving a durable response. Our paediatric patients responded better with most achieving a durable response. The treatment was safe for both groups of patients. Studies should be conducted to identify patients more likely to benefit from this treatment.

Evaluación del riesgo de fenómenos trombóticos tras el uso de factor VII activado / Risk assessment of thrombotic events after the use of activated factor VII

Introducción: El objetivo del estudio fue analizar la incidencia de efectos trombóticos relacionada con la administración de factor VII humano recombinante activo (rFVIIa) en el tratamiento de la hemorragia grave tras la cirugía cardiaca. Material y métodos: Estudio retrospectivo de casos-controles pareado, de 2 años de duración, que incluyó a 72 niños ingresados en cuidados intensivos y tratados con rFVIIa por una hemorragia grave, durante o tras la cirugía cardiaca. Utilizamos un grupo control de 63 pacientes, estadísticamente comparables en cuanto a sexo, peso, diagnóstico, riesgo quirúrgico según la clasificación RACHS-1 y las características quirúrgicas. Resultados: No existieron diferencias significativas en la incidencia de fenómenos trombóticos (20% en casos y 28% en controles, p = 0,540), ni en la mortalidad (16% en casos y 9,5% controles, p = 0,208). Conclusión: En nuestra serie, el tratamiento con rFVIIa ha demostrado ser útil en el control de la hemorragia incoercible en niños sometidos a cirugía cardiaca, y no parece aumentar el riesgo de fenómenos trombóticos ni la mortalidad en el periodo postoperatorio (AU)

Introduction: The objective of this study was to analyze the incidence of thrombotic complications related to recombinant human factor VII a (rFVIIa) therapy for severe postoperative bleeding in cardiac surgery. Material and methods: A retrospective matched case-control study was conducted over two years, including 72 children admitted to intensive care unit and treated with rFVIIa because of a severe bleeding during or after cardiac surgery. A control group of 63 patients was chosen, who were statistically comparable in sex, weight, diagnosis, surgical risk according RASCH-1 score, and surgical characteristics, was chosen. Results: There were no significant differences between cases and controls either in the rate of thrombosis (20% vs 28%, P=0.540), or in the mortality rate (16% vs 9.5%, P=0.208). Conclusions: In our study, the rFVIIa therapy was shown to be useful in controlling severe operative bleeding in pediatric cardiac surgery, but does not seem to increase the risk of thrombotic complications or mortality rate in the postoperative period (AU)

Asociación entre la exposición a paracetamol y el asma: estado de la cuestión y recomendaciones prácticas / Association between paracetamol exposure and asthma: update and practice guidelines

La prevalencia del asma ha aumentado en las últimas décadas, especialmente en los países desarrollados, por motivos no bien esclarecidos. En los últimos años se ha observado una asociación entre el uso de paracetamol en distintas etapas de la vida, incluyendo la gestación y la infancia, y la prevalencia de asma. El carácter observacional de los estudios publicados no permite establecer una relación causal. Sería necesario realizar ensayos clínicos para comprobar la naturaleza de la asociación, que podría deberse a la presencia de diversos factores de confusión. Las sociedades pediátricas españolas firmantes de este artículo consideran que los datos disponibles hasta la fecha no son suficientes para desaconsejar el uso de paracetamol durante la gestación ni en niños asmáticos o con riesgo de asma (AU)

Asthma prevalence has increased over the last few decades, especially in developed countries, and possibly due to different reasons. An association between paracetamol use or exposure at different periods of life, including gestation and childhood, and asthma prevalence has been observed in the last few years. Causality can not be established from observational reports, due to the arguable presence of many confounding factors and biases. Randomised trials are needed to elucidate the nature of this association. The Spanish Paediatric societies subscribing to this paper consider that current evidence is insufficient to discourage the use of paracetamol during gestation or in children with or at risk of asthma (AU)

Uso empírico de antibióticos en niños en España. Resultados de una Encuesta Pediátrica Nacional 2012 (Estudio ABES) / Results from the 2012 Paediatric National Survey on Empirical Use of Antibiotics in Children in Spain (ABES Study)

Introducción: Actualmente existen diversas guías nacionales sobre el uso empírico adecuado de antibióticos en niños. Desconocemos si los pediatras españoles emplean dichas guías al seleccionar antimicrobianos. Material y métodos: Estudio transversal de ámbito nacional, mediante encuesta on-line sobre la selección empírica de antibióticos en niños, enviada por correo electrónico a pediatras socios de la Asociación Española de Pediatría o de sus sociedades de especialidades y regionales, entre abril y junio del 2012. Para considerar la adecuación de las respuestas se tuvieron en cuenta las guías, los documentos de consenso y los protocolos recientes. Resultados: Se recibieron 1.214 respuestas. Los tratamientos seleccionados se ajustan en un 85% a las recomendaciones. Los resultados menos adecuados se obtienen en enfermedades infecciosas en las que no existe un documento de consenso nacional en el momento de realizar la encuesta (73% de adecuación en este caso). Conclusiones: La elección empírica de antibióticos por parte de los pediatras españoles es bastante adecuada a las guías recientes. Sin embargo, la interpretación de los datos debe ser crítica, ya que existen aspectos del manejo racional de antibióticos en niños que podrían mejorar en nuestro país. Se plantea como necesidad continuar con la realización e implementación de documentos de consenso nacionales para el manejo de enfermedades infecciosas pediátricas. Proponemos que este tipo de encuestas se realicen periódicamente, así como análisis similares en otras áreas de capacitación específicas, incluyendo estudios de prescripción real, para promover el uso racional de todos los fármacos pediátricos en nuestro país (AU)

Introduction: There are currently several national guidelines on the appropriate empirical use of antibiotics in Spanish children. But, do the Spanish paediatricians use these guidelines when prescribing antimicrobials. Material and methods: A national study from was conducted from April to June 2012 using an on-line questionnaire on the empirical selection of antibiotics in children. An e-mail was sent to paediatrician members of the Spanish Association of Paediatrics (AEP) or its Regional or Paediatric Specialties Societies. Current guidelines and consensus documents were used to determine the appropriateness of the responses. Results: A total of 1214 responses were received. Eighty five per cent of the treatments selected by Spanish paediatricians were adjusted to guidelines. The least appropriate responses were obtained in those infectious diseases with no national consensus document at the time of the survey (73% in this case). Conclusions: Spanish paediatricians mainly select empirical antibiotics in accordance with current guidelines. However, there are features that could be improved in our country. The preparing and implementation of national consensus documents on the management of paediatric infectious diseases should be continued. We propose to regularly perform these kinds of surveys, including real prescription studies, and to also extend it to other paediatric specialities, in order to promote appropriateness of use of all the paediatric drugs in our country (AU)

[Association between paracetamol exposure and asthma: update and practice guidelines]. / Asociación entre la exposición a paracetamol y el asma: estado de la cuestión y recomendaciones prácticas.

Asthma prevalence has increased over the last few decades, especially in developed countries, and possibly due to different reasons. An association between paracetamol use or exposure at different periods of life, including gestation and childhood, and asthma prevalence has been observed in the last few years. Causality can not be established from observational reports, due to the arguable presence of many confounding factors and biases. Randomised trials are needed to elucidate the nature of this association. The Spanish Paediatric societies subscribing to this paper consider that current evidence is insufficient to discourage the use of paracetamol during gestation or in children with or at risk of asthma.

[Results from the 2012 Paediatric National Survey on Empirical Use of Antibiotics in Children in Spain (ABES Study)]. / Uso empírico de antibióticos en niños en España. Resultados de una Encuesta Pediátrica Nacional 2012 (Estudio ABES).

INTRODUCTION: There are currently several national guidelines on the appropriate empirical use of antibiotics in Spanish children. But, do the Spanish paediatricians use these guidelines when prescribing antimicrobials? MATERIAL AND METHODS: A national study from was conducted from April to June 2012 using an on-line questionnaire on the empirical selection of antibiotics in children. An e-mail was sent to paediatrician members of the Spanish Association of Paediatrics (AEP) or its Regional or Paediatric Specialties Societies. Current guidelines and consensus documents were used to determine the appropriateness of the responses. RESULTS: A total of 1214 responses were received. Eighty five per cent of the treatments selected by Spanish paediatricians were adjusted to guidelines. The least appropriate responses were obtained in those infectious diseases with no national consensus document at the time of the survey (73% in this case). CONCLUSIONS: Spanish paediatricians mainly select empirical antibiotics in accordance with current guidelines. However, there are features that could be improved in our country. The preparing and implementation of national consensus documents on the management of paediatric infectious diseases should be continued. We propose to regularly perform these kinds of surveys, including real prescription studies, and to also extend it to other paediatric specialities, in order to promote appropriateness of use of all the paediatric drugs in our country.

[Risk assessment of thrombotic events after the use of activated factor VII]. / Evaluación del riesgo de fenómenos trombóticos tras el uso de factor vii activado.

INTRODUCTION: The objective of this study was to analyze the incidence of thrombotic complications related to recombinant human factor viia (rFVIIa) therapy for severe postoperative bleeding in cardiac surgery. MATERIAL AND METHODS: A retrospective matched case-control study was conducted over two years, including 72 children admitted to intensive care unit and treated with rFVIIa because of a severe bleeding during or after cardiac surgery. A control group of 63 patients was chosen, who were statistically comparable in sex, weight, diagnosis, surgical risk according RASCH-1 score, and surgical characteristics, was chosen. RESULTS: There were no significant differences between cases and controls either in the rate of thrombosis (20% vs 28%, P=.540), or in the mortality rate (16% vs 9.5%, P=.208). CONCLUSIONS: In our study, the rFVIIa therapy was shown to be useful in controlling severe operative bleeding in pediatric cardiac surgery, but does not seem to increase the risk of thrombotic complications or mortality rate in the postoperative period.

Formación pediátrica para el desarrollo de actividades clínicas / Paediatric training for developing clinical activities

Resumen El farmacéutico, por su formación general en el ámbito de la Farmacia Hospitalaria, tiene la capacidad para analizar e implantar mejoras en los circuitos de prescripción, dispensación y administración de medicamentos, lo cual repercute en la mejora de la seguridad global en la utilización de medicamentos. El objetivo principal del farmacéutico pediátrico es mejorar la calidad asistencial del paciente mediante una atención individualizada a través de la validación de las prescripciones médicas y del seguimiento farmacoterapéutico, que permita una farmacoterapia efectiva, segura y eficiente. Esta revisión nace del fruto de una experiencia multidisciplinar entre el Servicio de Farmacia y la Unidad de Cuidados Intensivos Pediátricos, cuyos objetivos fueron analizar el papel del farmacéutico residente en la UCIP para establecer líneas de mejora en sus actividades que potencien el uso racional del medicamento y diseñar un programa docente para el farmacéutico pediátrico que pueda servir como modelo inicial para otros centros (AU)

The general training received by pharmacists in Hospital Pharmacy enables them to analyse and implement improvements in the prescription, dispensing and administration of medications. This may lead to an increase in the overall safety of the use of drugs. The main goal of the paediatric pharmacist is to improve patient care by greater attention to the individual via validation of medical prescriptions and pharmaceutical follow-up, leading to safe, effective and efficient pharmacotherapy. This is a multidisciplinary review by the Pharmacy Department and Paediatric Intensive Care Unit. The objectives were to analyse the role of a resident pharmacist in PICU to identify improvements to promote rational drug use, and to design a teaching program for paediatric pharmacists that may serve as a reference for other centres (AU)

Validation of a method for recording pharmaceutical interventions.

WHAT IS KNOWN AND OBJECTIVE: The validation of a method for recording pharmaceutical interventions measures the instrument's ability to provide consistent values when the same analysis is performed several times. Our aim was to validate the inter-rater reliability of the method used to record pharmaceutical interventions in our hospital. METHODS: We recorded interventions in a database, entering variables related to the patient, treatment and impact of the recommendation. We also recorded the type, cause and clinical significance of the negative outcome associated with use of the medicinal product (NOM). Twenty interventions performed during a 3-year study period (2007-2009) were randomly tested for consistency to analyse the kappa (κ) coefficient statistic of the recommendations as coded by nine senior and junior clinical pharmacists. RESULTS AND DISCUSSION: There were 87·8% global consistency for NOM cause, 66·1% for intervention impact and 95·0% for NOM type. Agreement was substantial for 'intervention reasons', with a κ value of 0·74 (95%CI 0·61-0·87), fair for 'intervention impact', with a κ value of 0·24 (95%CI 0·15-0·32) and excellent for 'NOM type', with a κ value of 0·87 (95%CI 0·71-1·00), respectively. Our results are globally good, especially with regard to the analysis of intervention reasons and NOM type, which matches other authors' findings. Furthermore, our validation method is suitable for recording and considering the impact of pharmaceutical interventions. WHAT IS NEW AND CONCLUSION: We describe a systematic method for clinical pharmacists to record their activities and assess their value. This methodology should help in the development of clinical pharmacy in Spain and should be translatable to other settings.

[Profile of parenteral nutrition prescription in very low birth weight infants: period 2006 to 2010]. / Perfil de prescripción de nutrición parenteral en recién nacidos de muy bajo peso al nacer: período 2006 a 2010.

INTRODUCTION: Early administration of nutrients in adequate amounts is of vital importance to preterm infants because it decreases the time needed to reach the expected weight and tolerate enteral nutrition as well as reducing their hospital stay. The main objective of this study was to analyze the prescription of parenteral nutrition (PN) in patients weighing less than 1,500 g at birth in their first 7 days of life during the years 2006-2010 in our hospital and the adequacy of those requirements to the recommendations. MATERIALS AND METHODS: Amino acids, glucose, lipids (g/ kg/day) and calories (kcal/kg/day) prescribed in the PN of the first week of life were collected. RESULTS: We studied 1899 parenteral nutrition prescriptions from 2006 to 2010 corresponding to the first week of life of 360 patients weighing less than 1,500 g. The caloric content increased from an average of 41.83 kcal/kg/day (1.89 g/kg/ day of amino acids and 0.69 g/kg/day lipids) on the first day of life to 80.61 kcal/kg/day (3.2 g/kg/day of amino acids and 2.4 g/kg/day of lipids) on the seventh day. About 70% of prescriptions for the children who had PN on the first day of life contained lipids. But when all children who had PN on the fourth day were considered, only 17% of these patients had lipid intake on the first day of life. No prescription exceeded 120 kcal/kg/day. Only 17.9% on the sixth day and 25.5% on the seventh day received more than 90 kcal/kg/day. In our hospital PN is not prepared on Sundays and holidays. 30.1% and 56.9% of children born on weekdays received PN the first and second day versus 11.6% and 38.8% of those born on a holiday or the day before holiday. CONCLUSIONS: A high percentage of premature babies do not get the recommended amounts of nutrients in their first week of life in our hospital.

[Paediatric training for developing clinical activities]. / Formación pediátrica para el desarrollo de actividades clínicas.

The general training received by pharmacists in Hospital Pharmacy enables them to analyse and implement improvements in the prescription, dispensing and administration of medications. This may lead to an increase in the overall safety of the use of drugs. The main goal of the paediatric pharmacist is to improve patient care by greater attention to the individual via validation of medical prescriptions and pharmaceutical follow-up, leading to safe, effective and efficient pharmacotherapy. This is a multidisciplinary review by the Pharmacy Department and Paediatric Intensive Care Unit. The objectives were to analyse the role of a resident pharmacist in PICU to identify improvements to promote rational drug use, and to design a teaching program for paediatric pharmacists that may serve as a reference for other centres.

Setting up an emergency stock for metabolic diseases.

INTRODUCTION: Therapeutic management of inborn errors of metabolism (IEMs) is complicated. The drugs involved are classified as orphan, and their supply depends on whether they are orphan medicines, investigational drugs, or need to be prepared as a compounded formula. MATERIALS AND METHODS: We analyzed emergency criteria, availability, and permanent location of metabolic drugs within the hospital. Information on therapeutic usage, administration, and dosage was also recorded. RESULTS: A stock for treating IEMs should include chelating agents, drugs to treat deficiencies, enzyme supplements, and other specific treatments. Hyperammonemia was considered to be life-threatening; therefore, an emergency supply of drugs to treat this condition should be kept permanently in the hospitalization unit. CONCLUSIONS: Emergency drug stocks are highly recommended in tertiary hospitals in order to improve care for patients susceptible to IEM.