Educational interventions in pharmacovigilance to improve the knowledge, attitude and the report of adverse drug reactions in healthcare professionals: Systematic Review and Meta-analysis.

OBJECTIVES: Underreporting of adverse drug reactions (ADRs) limits and delays the detection of signs. The aim of this systematic review with meta-analyses was to synthesize the evidence of educational interventions (EIs) efficacy in health professionals to increase ADR reporting, attitudes, and knowledge of pharmacovigilance. EVIDENCE ACQUISITION: A systematic literature review was carried out to identify randomized clinical trials evaluating the efficacy of EI in pharmacovigilance in health professionals to improve ADR reports, knowledge, and attitude toward pharmacovigilance. ADR reports were pooled by calculating Odds Ratio (OR) with a 95% confidence interval (95%CI), while pharmacovigilance knowledge and attitude were pooled by calculating a mean difference (MD) with 95%CI. In addition, the subanalysis was performed by EI type. Meta-analysis was performed with RevMan 5.4 software. PROSPERO registry CRD42021254270. RESULTS: Eight hundred seventy-five articles were identified as potentially relevant, and 11 were included in the systematic review. Metanalysis showed that EI increased ADR reporting in comparison with control group (OR = 4.74, [95%CI, 2.46 to 9.12], I2 = 93%, 5 studies). In subgroup analysis, the workshops (OR = 6.26, [95%CI, 4.03 to 9.73], I2 = 57%, 3 studies) increased ADR reporting more than telephone-based interventions (OR = 2.59, [95%CI, 0.77 to 8.73], I2 = 29%, 2 studies) or combined interventions (OR = 5.14, [95%CI, 0.97 to 27.26], I2 = 93%, 3 studies). No difference was observed in pharmacovigilance knowledge. However, the subanalysis revealed that workshops increase pharmacovigilance knowledge (SMD = 1.85 [95%CI, 1.44 to 2.27], 1 study). Only one study evaluated ADR reporting attitude among participants and showed a positive effect after the intervention. CONCLUSION: EI improves ADR reports and increases pharmacovigilance knowledge. Workshops are the most effective EI to increase ADR reporting.

Incidence, severity, and preventability of adverse events during the induction of patients with acute lymphoblastic leukemia in a tertiary care pediatric hospital in Mexico.

Healthcare-associated adverse events represent a heavy burden of symptoms for pediatric oncology patients. Their description allows knowing the safety and quality of the care processes in countries with limited resources. This study aimed to describe the incidence, types, severity, and preventability of adverse events occurring in pediatric patients with acute lymphoblastic leukemia during the induction phase in a tertiary care pediatric hospital in Mexico. This study analyzed a cohort based on medical records of between 2015 and 2017. Initially, information on patients and adverse events was collected; subsequently, two pediatric oncologist reviewers independently classified adverse events, severity and preventability. Agreement between reviewers was evaluated. Adverse events incidence rates were estimated by type, severity, and preventability. One-hundred and eighty-one pediatric patients pediatric patients with acute lymphoblastic leukemia were studied. An overall adverse events rate of 51.8 per 1000 patient-days was estimated, involving 81.2% of patients during induction. Most adverse events were severe or higher (52.6%). Infectious processes were the most common severe or higher adverse event (30.5%). The presence of adverse events caused 80.2% of hospital readmissions. Of the adverse events, 10.5% were considered preventable and 53.6% could be ameliorable in severity. Improving the safety and quality of the care processes of children with acute lymphoblastic leukemia is possible, and this should contribute to the mitigation and prevention of adverse events associated morbidity and mortality during the remission induction phase.

Prevalence and types of drug interactions in hospitalized pediatric patients in Mexico City.

OBJECTIVE: Drug-drug interactions may modify the therapeutic effect or the safety profile of the medicines used in pediatric populations.  Although interest on potential drug interactions in these age groups has  increased, information on clinically relevant drug-drug interactions is still  scarce. The aim of this study was to explore the prevalence and  characteristics of potential and clinically relevant drug-drug interactions  among pediatric patients hospitalized in two pediatric hospitals of Mexico  City. METHOD: A cross-sectional study was conducted on patient records in critical, oncological, burns and other non-critical services by a pediatric resident physician at both hospitals. Micromedex® was used as a source of potential drug-drug interactions data. Subsequently, each  interaction's prevalence, severity and evidence level were estimated.  Additionally, drug-drug interaction causality with regard to diverse clinical  outcomes of hospitalized patients was determined through the Drug  Interaction Probability Scale. The clinical consequences of each interaction  were classified by severity. RESULTS: The observed prevalence of one or more potential drug-drug interactions in hospitalized patients was 61.3% (52.2-70.4%), whilst  the prevalence of real drug-drug interactions was 3.6% (0.1-7.1%). Of  potential drug-drug interactions, 60.5% were considered major and only  5.1% contraindicated. These were generally more common in intensive  care and burn units. The main pharmacological agents involved in  potential drug-drug interactions were opioids analgesics and anti-infective  and neurologic agents. Four clinically relevant drug-drug interactions  required a regimen change and another prompted an extension of the  patient's hospital stay. CONCLUSIONS: Potential drug-drug interactions were common in the pediatric patients studied, whereas the frequency of real drug-drug  interactions was low. However, some drug-drug interactions required  medical actions in addition to routine monitoring. More information is  needed on real drug-drug interactions as those related to failed efficacy  might be underestimated.

Objetivo: Las interacciones fármaco-fármaco pueden modificar el efecto terapéutico o la seguridad de los medicamentos usados en  poblaciones pediátricas. Aunque el interés sobre interacciones potenciales  en estos grupos etarios viene incrementando, aún es escasa la información sobre interacciones fármaco-fármaco que se manifiestan clínicamente en el paciente (reales). El propósito de este estudio fue explorar la prevalencia y características de las interacciones fármaco-fármaco potenciales y reales  en pacientes ingresados en dos hospitales pediátricos de la Ciudad de  México.Método: Se llevó a cabo un estudio transversal en expedientes de  pacientes atendidos en servicios críticos, oncológicos, de quemados y otros no críticos por un médico residente de pediatría en ambos hospitales. Se  usó Micromedex® como fuente de datos de interacciones potenciales,  luego se estimó su prevalencia por paciente, gravedad y nivel de  evidencia. Adicionalmente, se determinó la causalidad de las interacciones  fármaco-fármaco con diversos desenlaces clínicos de los pacientes  hospitalizados mediante la Drug Interaction Probability Scale, y finalmente  se clasificaron por gravedad.Resultados: La prevalencia observada de pacientes hospitalizados con  una o más interacciones fármaco-fármaco potenciales fue del 61,3% (52,5­70,4%), mientras que la prevalencia de interacciones  fármaco-fármaco reales fue del 3,6% (0,1-7,1%). Entre las interacciones  potenciales, el 60,5% se consideraron importantes y sólo el 5,1%  contraindicadas. En general, las interacciones fármaco-fármaco potenciales fueron más comunes en los servicios de cuidados intensivos y de  quemados. Los principales grupos farmacológicos involucrados en  interacciones potenciales fueron agentes analgésicos opioides, antibióticos  y neurológicos. Cuatro interacciones reales requirieron modificación de la  farmacoterapia y una prolongó la estancia hospitalaria.Conclusiones: Las interacciones potenciales fueron comunes en los pacientes pediátricos estudiados, mientras que la frecuencia de  interacciones reales fue baja; sin embargo, sus consecuencias requirieron  acciones médicas adicionales a la monitorización habitual. Se requiere más información sobre las interacciones reales, aquellas referidas a faltas de  eficacia podrían estar subestimadas.

Prevalencia y tipos de interacciones farmacológicas en pacientes pediátricos hospitalizados en la Ciudad de México / Prevalence and types of drug interactions in hospitalized pediatric patients in Mexico City

Objetivo: Las interacciones fármaco-fármaco pueden modificar el efectoterapéutico o la seguridad de los medicamentos usados en poblacionespediátricas. Aunque el interés sobre interacciones potenciales en estos grupos etarios viene incrementando, aún es escasa la información sobre interacciones fármaco-fármaco que se manifiestan clínicamente en el paciente(reales). El propósito de este estudio fue explorar la prevalencia y características de las interacciones fármaco-fármaco potenciales y reales en pacientes ingresados en dos hospitales pediátricos de la Ciudad de México.Método: Se llevó a cabo un estudio transversal en expedientes de pacientes atendidos en servicios críticos, oncológicos, de quemados y otros nocríticos por un médico residente de pediatría en ambos hospitales. Se usóMicromedex® como fuente de datos de interacciones potenciales, luego seestimó su prevalencia por paciente, gravedad y nivel de evidencia. Adicionalmente, se determinó la causalidad de las interacciones fármaco-fármacocon diversos desenlaces clínicos de los pacientes hospitalizados mediante laDrug Interaction Probability Scale, y finalmente se clasificaron por gravedad.Resultados: La prevalencia observada de pacientes hospitalizadoscon una o más interacciones fármaco-fármaco potenciales fue del 61,3%(52,5-70,4%), mientras que la prevalencia de interacciones fármaco-fármacoreales fue del 3,6% (0,1-7,1%). Entre las interacciones potenciales, el 60,5%se consideraron importantes y sólo el 5,1% contraindicadas. (AU)

Objective: Drug-drug interactions may modify the therapeutic effect orthe safety profile of the medicines used in pediatric populations. Althoughinterest on potential drug interactions in these age groups has increased,information on clinically relevant drug-drug interactions is still scarce. Theaim of this study was to explore the prevalence and characteristics ofpotential and clinically relevant drug-drug interactions among pediatricpatients hospitalized in two pediatric hospitals of Mexico City.Method: A cross-sectional study was conducted on patient records incritical, oncological, burns and other non-critical services by a pediatricresident physician at both hospitals. Micromedex® was used as a sourceof potential drug-drug interactions data. Subsequently, each interaction’sprevalence, severity and evidence level were estimated. Additionally,drug-drug interaction causality with regard to diverse clinical outcomes ofhospitalized patients was determined through the Drug Interaction Probability Scale. The clinical consequences of each interaction were classifiedby severity.Results: The observed prevalence of one or more potential drug-druginteractions in hospitalized patients was 61.3% (52.2-70.4%), whilst theprevalence of real drug-drug interactions was 3.6% (0.1-7.1%). Of potential drug-drug interactions, 60.5% were considered major and only 5.1%contraindicated. (AU)

Descriptive study of adverse drug reactions in a tertiary care pediatric hospital in México from 2014 to 2017.

INTRODUCTION: In Pediatrics, adverse drug reactions (ADRs) affect morbidity and mortality. In Mexico, the characteristics of ADRs and suspect drugs have not been described in hospitalized children. OBJECTIVE: To estimate the frequency of ADRs and describe them, as well as suspect drugs, in a tertiary care pediatric hospital in Mexico. METHODS: A total of 1,649 Hospital Infantil de Mexico Federico Gómez ADR reports were analyzed. Completeness of the information was assessed, and ADRs severity and seriousness were assigned based on NOM-220-SSA1-2012, with causality being established according to the Naranjo algorithm. ADRs were classified with WHO Adverse Drug Reaction Terminology (WHO-ART). The drugs involved in ADRs were categorized according to the Anatomical Therapeutic Chemical (ATC) classification. Descriptive analysis was performed using the SPSS 20 statistical package. RESULTS: Of all the reports, 5.8% lacked sufficient information for the analysis (grade 0). ADRs frequency ranged from 2.12% to 8.07%. ADRs occurred most commonly in children (56.9%), in the female gender (52%), in subjects with normal BMI Z-score (46.6%) and malnutrition (35.3%), diagnosed with neoplasms (72.2%) and in the Emergency Department (70.0%). ADRs were severe in 14.4% of cases, in 81.0% they were serious and 2.1% were classified as definite. Most common serious ADR was febrile neutropenia (44.5%). The 0.7% of patients recovering with sequelae; 1.1% died (with the medication being associated) and 70.3% were admitted to the hospital as a result of an ADR. Antineoplastic and immunomodulating agents were more commonly associated with serious ADRs. CONCLUSION: ADRs affected morbidity and mortality, which is why strengthening pharmacovigilance programs in Mexican pediatric hospitals is necessary.

Medication errors in a cohort of pediatric patients with acute lymphoblastic leukemia on remission induction therapy in a tertiary care hospital in Mexico.

INTRODUCTION: Medication errors (MEs) are the main type of preventable adverse events in medical care, as well as safety indicators in the medication processes. Advances in the quality of care in pediatric acute lymphoblastic leukemia (ALL) have enabled to improve clinical outcomes. However, ME epidemiology in pediatric oncology is still incipient in developing countries. In view of this, the objectives of this study were to estimate the incidence of MEs, determine their types and consequences, as well as their preventability in the induction treatment of children with ALL at Hospital Infantil de Mexico Federico Gómez. METHODS: We reviewed the remission-induction chemotherapy records of children with ALL between January 2015 and December 2017. A two-phase review was carried out for ME identification and verification. The consequences of errors were determined by agreement between reviewers. RESULTS: We reviewed 1762 chemotherapy orders involving 181 children. MEs were observed in 16.9% of orders and in 57.5% of patients. Prescription errors were the most common (93.3%), with wrong dose errors (90.2%) being predominant. Only 3.7% of wrong dose errors were intercepted, while 12.2% of the children experienced adverse drug events (ADEs) preceded by some wrong dose error. CONCLUSIONS: MEs were common, since they occurred in 57.5% of children with ALL on induction treatment and involved 16.5% of chemotherapy orders. Only 3.7% of MEs were intercepted, while 12.2% of children had ADEs related to overdose. Measures are required to prevent calculation error in prescriptions, as well as training of the nursing staff to intercept MEs.

Potential drug-drug interactions and their risk factors in pediatric patients admitted to the emergency department of a tertiary care hospital in Mexico.

BACKGROUND: Drug-drug interactions (DDIs) detected in a patient may not be clinically apparent (potential DDIs), and when they occur, they produce adverse drug reactions (ADRs), toxicity or loss of treatment efficacy. In pediatrics, there are only few publications assessing potential DDIs and their risk factors. There are no studies in children admitted to emergency departments (ED). The present study estimates the prevalence and describes the characteristics of potential DDIs in patients admitted to an ED from a tertiary care hospital in Mexico; in addition, potential DDI-associated risk factors are investigated. METHODS: A secondary analysis of data from 915 patients admitted to the ED of the Hospital Infantil de México "Federico Gómez" was conducted. The Medscape Drug Interaction Checker software was used to identify potential DDIs. The results are expressed as number of cases (%), means (95% CI) and medians (25-75th percentiles). Count data regressions for number of total and severity-stratified potential DDIs were performed adjusting for patient characteristics, number of administered drugs, days of stay, presence of ADRs and diagnoses. RESULTS: The prevalence of potential DDIs was 61%, with a median of 4 (2-8). A proportion of 0.2% of potential DDIs was "Contraindicated", 7.5% were classified as "Serious", 62.8% as "Significant" and 29.5% as "Minor". Female gender, age, days of stay, number of administered drugs and diagnoses of Neoplasms (C00-D48), Congenital malformations (Q00-Q99), Diseases of the Blood, Blood-forming Organs and Immunity (D50-D89) and Diseases of the nervous system (G00-G99) were significantly associated with potential DDIs. CONCLUSION: The prevalence of potential DDIs in the ED is high, and strategies should therefore be established to monitor patients' safety during their stay, in addition to conducting investigations to estimate the real harm potential DDIs inflict on patients.

A comprehensive intervention for adverse drug reactions identification and reporting in a Pediatric Emergency Department.

BACKGROUND: Physicians identify from 45.7 to 96.2 % of Adverse Drug Reactions (ADRs) in their patients, with under-reporting ranging from 6 to 100 %. In order to improve ADR reporting, several interventions have been evaluated in different studies, but not with regard to ADR identification. In addition, it is not known whether some patient characteristics might influence on ADR identification and reporting by physicians. OBJECTIVES: (a) To assess the effectiveness of a comprehensive intervention directed to Emergency Department physicians and coordinated by a pharmacist in a tertiary care pediatric hospital on ADR identification and reporting. (b) To assess if some of the children's characteristics might influence on ADR identification and reporting. Setting The Emergency Department of the Hospital Infantil de México "Federico Gómez", which is a national pediatric institute of health in México. METHODS: A Quasi-experimental, pre-post test trial was designed. During the intervention, the pharmacist gave talks on Pharmacovigilance and on the program for electronic capture of data, took part in patient visits, left reminders, improved accessibility to ADR report format and performed feedback activities. To classify and quantify correctly identified ADRs and ADRs reported to the Institutional Pharmacovigilance Center (IPC), 1136 clinical records were reviewed. The models were adjusted for patient variables. MAIN OUTCOME MEASURES: Total ADRs, ADRs correctly identified by physicians, ADRs reported to the IPC by physicians. Results Before the intervention, 97 % of ADRs were correctly identified and 6.1 % reported by physicians. During the intervention, 99.6 % were correctly identified and 41.2 % were reported, and after the intervention, 99.6 and 41.7 %, respectively. Identification during the intervention showed a sevenfold increase with regard to preintervention and was maintained post-intervention. ADR reporting during the intervention showed a 14-fold increase with regard to pre-intervention and was maintained during post-intervention. CONCLUSION: Physicians do identify ADRs, but fail to report them. The intervention increased ADR correct identification and reporting. The effect was maintained after the intervention.

¿Los pediatras detectan las reacciones adversas a medicamentos aunque no las reporten? / Do pediatricians identify adverse drug reactions even when they do not report them?

Resumen:Introducción: La notificación espontánea depende de la capacidad de los médicos de detectar las reacciones adversas a medicamentos (RAM) y del hábito de reportarlas. En 2008 y 2009, la frecuencia de reportes de RAM al Programa Electrónico de Farmacovigilancia (SISFAR) del total de egresos del Hospital Infantil de México Federico Gómez fueron bajas (0.44 y 0.20%, respectivamente). Por esta razón, en el 2010 se decidió evaluar la capacidad de los médicos de identificar las RAM utilizando como estrategia la revisión de los expedientes clínicos.Métodos: Se llevó a cabo un estudio observacional, descriptivo, transversal y retrospectivo en el Departamento de Urgencias (DU), del 1 de marzo al 31 de agosto del 2010. Se clasificaron y cuantificaron como RAM identificadas por los médicos cuando existió evidencia por escrito en el expediente clínico de que ellos habían asociado una manifestación clínica con una RAM, incluyendo además la evaluación del número de reportes al SISFAR. Se realizó el análisis descriptivo con SPSS versión 18.Resultados: La frecuencia de RAM de los pacientes que ingresaron al DU fue del 21.8%. El 86% de ellas fueron identificadas por los médicos en el expediente clínico y el 14% por el farmacéutico. Se reportó solamente el 6.1% al SISFAR.Conclusiones: Aunque fue elevada la identificación de las RAM en el expediente clínico, es posible que existan algunas que no se hayan detectado. Por otra parte, se confirmó el elevado grado de subreporte al SISFAR, por lo que se requieren acciones para fomentar el hábito del reporte.

Abstract:Introduction: Spontaneous notification depends on the ability of pediatricians to identify adverse drug reactions (ADRs) along with their habit of reporting these incidents. During the years 2008 and 2009, the frequency of reports of ADRs to the Electronic Program of Pharmacovigilance (SISFAR) in the Hospital Infantil of Mexico Federico Gomez (HIMFG) was low (0.44% and 0.20%, respectively). Because of the above, the ability of pediatricians from the Emergency Department (ED) to identify ADRs using the clinical chart review was evaluated in 2010 in this study.Methods: A descriptive, observational, cross-sectional retrospective study was conducted in the ED from March 1 to August 31. ADRs were classified and quantified as "ADRs identified by pediatricians" when there was evidence in the clinical chart that pediatricians associated a clinical sign, symptom and laboratory value with an ADR. The numbers of notifications reported in SISFAR were quantified. Descriptive analysis was done using SPSS v.18.Results: Considering patients who were admitted to the ED, the frequency of ADRs was 21.8%. The frequency of ADRs identified by physicians in clinical charts was 86%. The pharmacist detected 14% of ADRs. The frequency of ADRs reported by physicians was 6.1%.Conclusions: Although identification of ADRs in the clinical charts by pediatricians was high, it is possible that some ADRs were undetected. Because underreporting was very high, it is necessary to take actions to improve the reporting process.

[Do pediatricians identify adverse drug reactions even when they do not report them?] / ¿Los pediatras detectan las reacciones adversas a medicamentos aunque no las reporten?

INTRODUCTION: Spontaneous notification depends on the ability of pediatricians to identify adverse drug reactions (ADRs) along with their habit of reporting these incidents. During the years 2008 and 2009, the frequency of reports of ADRs to the Electronic Program of Pharmacovigilance (SISFAR) in the Hospital Infantil of Mexico Federico Gomez (HIMFG) was low (0.44% and 0.20%, respectively). Because of the above, the ability of pediatricians from the Emergency Department (ED) to identify ADRs using the clinical chart review was evaluated in 2010 in this study. METHODS: A descriptive, observational, cross-sectional retrospective study was conducted in the ED from March 1 to August 31. ADRs were classified and quantified as "ADRs identified by pediatricians" when there was evidence in the clinical chart that pediatricians associated a clinical sign, symptom and laboratory value with an ADR. The numbers of notifications reported in SISFAR were quantified. Descriptive analysis was done using SPSS v.18. RESULTS: Considering patients who were admitted to the ED, the frequency of ADRs was 21.8%. The frequency of ADRs identified by physicians in clinical charts was 86%. The pharmacist detected 14% of ADRs. The frequency of ADRs reported by physicians was 6.1%. CONCLUSIONS: Although identification of ADRs in the clinical charts by pediatricians was high, it is possible that some ADRs were undetected. Because underreporting was very high, it is necessary to take actions to improve the reporting process.

Tendencias del consumo y precio promedio ponderado sobre los costos de los medicamentos anti-infecciosos en un hospital pediátrico / Tendency of the consumption and weighted average price over the cost of anti-infective drugs in a pediatric hospital

Introducción. Se evalúa la tendencia de consumo, precio promedio ponderado (PPP) y costo total, así como la influencia del consumo y PPP sobre los costos totales, en los subgrupos de medicamentos (dosis diaria definida/100 días-cama) antibacterianos, antimicóticos, antimicobacterianos y antivirales de 2005 a 2007. Métodos. De la base de datos de la farmacia del hospital, se calcularon, para cada medicamento, su consumo, PPP y costo total de los cuatro subgrupos terapéuticos. El análisis estadístico fue regresión lineal múltiple y coeficiente de correlación de Spearman. Resultados. El subgrupo con mayor consumo y costo fue el de antibacterianos, y el de mayor precio ponderado el de los antivirales. Se identificó que el consumo y los precios ponderados influyeron significativamente en los costos totales. El cambio por cada unidad de consumo y de precio ponderado produjo un incremento de $190,893.8 USD (IC95% 118,196.1-263,591.6) y de $3,050.4 USD (IC95% 1,912.5-4,188.3), respectivamente. Conclusiones. El aumento porcentual progresivo del costo de los antiinfecciosos en comparación con el total de grupos terapéuticos del hospital fue consecuencia del consumo y de los PPP. El análisis estadístico empleado y el uso de las variaciones porcentuales permitieron identificar, por subgrupos terapéuticos, el efecto que los consumos y los PPP tienen sobre los costos totales. El análisis individual de los medicamentos de alto costo también permitió interpretar algunos comportamientos; por lo que se recomienda efectuar este tipo de evaluaciones para identificar las diversas variables que influyen en los costos.

Background. We undertook this study to evaluate the tendency of the consumption (defined as daily doses/100 bed-days), the weighted average price (WAP) and the total cost of antibacterials, antimycotics, antimycobacterials and antiviral subgroups from 2005 to 2007, as well as the influence of the consumption and the WAP on the total costs. Methods. We used the database of the hospital pharmacy in order to calculate consumption, WAP and total cost of each drug for therapeutic subgroups. Multiple linear regression and Spearman correlation coefficient were used for statistical analyses. Results. The antibacterial subgroup showed the highest consumption and the total cost. The antiviral subgroup showed the highest WAP. Consumption and WAP had a significant influence on the total costs. The change by each unit of consumption and WAP produced an increase of 190,893.8 USD (95% CI 118,196.1-263,591.6) and 3,050.4 USD (95% CI 1,912.5-4,188.3), respectively. Conclusion. The progressive percentage increase of the total cost of anti-infective drugs in comparison with the total cost of hospital's therapeutic subgroups was due to the consumption and WAP. Statistical analysis and percentage of variations can identify the effect of consumption and WAP on total costs according to therapeutic subgroups. The analysis of high-cost drugs allows interpretation of some behaviors. Therefore, it is recommended to carry out these types of evaluations so as to identify the different variables that can influence costs.