Este estudio aporta datos sobre la incidencia de errores de conciliación al ingreso hospitalario de pacientes onco-hematológicos pediátricos. Analiza además las posibles variables implicadas en la aparición de este tipo de errores (demográficas, derivadas de la complejidad del tratamiento…) y realiza un análisis univariante para determinar el peso que cada una de esas variables pudiera tener sobre el riesgo de aparición de un error de conciliación.

Los resultados de este estudio permitirán el desarrollo de estrategias de selección y priorización de pacientes susceptibles de sufrir errores de conciliación en las transiciones asistenciales. De esta manera los farmacéuticos implicados en el cuidado de la población pediátrica onco-hematológica podrán incluir la conciliación de la medicación como una herramienta más en el proceso de atención farmacéutica de estos pacientes.

The drug utilization process is typically complex and error-prone, and involves several stages. Medication errors (MEs) are defined as any preventable event occurring through action, or the lack of action, at any stage of the of the medication use process, which may or may not result in harm to the patient.1 Up to 60% of MEs occur during care transitions.2

According to Medication safety in transitions of care, a technical report published in 2017 by the World Health Organization (WHO),3 between 3 and 97% of adult patients and between 22 and 72% of pediatric patients experience at least one medication discrepancy on admission. The report therefore proposes to improve safety in three main areas, including transitions of care, particularly for vulnerable patients. Pediatric patients play an important role within this category4 as they are exposed to three times more potential adverse events (AEs)5 and are much less tolerant of MEs than adults.

One of the main strategies proposed to reduce the incidence of MEs during care transitions is medication reconciliation (MR), a process whose implementation and development has been promoted by various Spanish and international institutions, such as the WHO,6 the Institute for Safe Medication Practices (ISMP),7 the National Institute for Health and Care Excellence (NICE),8 the Joint Commission on Accreditation of Healthcare Organizations (JCAHO),9 the Spanish Ministry of Health,10 and the Health Service of the Community of Madrid.11

MR has been defined as the formal and standardized process of obtaining a complete list of the medications a patient was taking prior to the last transition of care, comparing it with the patient's active prescription, and resolving any discrepancies to ensure that patients receive the medication required for any chronic conditions they may have, adapted to their current clinical situation.12 The MR process consists of several stages13 aimed at obtaining a complete list of the medications a patient is taking. Obtaining this list is a complex endeavor, and is the key part of the MR process. The rest of the process depends on the quality of the medication list obtained. A discrepancy is any difference between the medication a patient was taking at home before the last transition of care and the medication prescribed in hospital. A discrepancy in itself is not necessarily an error. In fact, most discrepancies are usually due to the need to adjust the patient's chronic medication to their new clinical status or to the need for the patient to undergo tests or procedures with which their usual medication could interfere. These are known as justified discrepancies. When discrepancies do not respond to a voluntary adjustment of the medication to the patient's new clinical situation, they are considered to be reconciliation errors (REs).

Between 2004 and 2019, more than 300 articles were published on on-admission MR in adult patients, while only 17 were published in the pediatric population, and none of them in Spain. Analysis of a representative sample of these articles shows that 23%–87% of the adult patients studied had at least one ME performed on admission. Similarly, the percentage of pediatric patients who had at least one RE ranged from 7% to72%.14–17

The risk of error at the different stages of the drug use process is significantly higher in the case of complex chronic patients. The management of hemato-oncological conditions requires the use of a large number of drugs, many of which have a narrow therapeutic index, a large number of drug–drug interactions, and an increased risk of adverse effects, all of which tend to lead to frequent hospitalizations during the course of treatment because of complications arising from the conditions themselves or the treatment regimens required. In this regard, Iturgoyen et al.18 have shown that patients with hemato-oncologic conditions are at a higher risk of MEs, and should be prioritised in the medication reconciliation process.

For the above reasons, and considering that the published data on pediatric patients, albeit much smaller in number, show a similar prevalence of REs in children and adults, the present study sought to determine the prevalence of on-admission REs in a group of pediatric hemato-oncologic patients to find out whether these patients are as susceptible to on-admission REs, i.e., whether an MR program for newly admitted pediatric hemato-oncologic patients could be as useful in preventing REs as in the adult population.

This was a prospective multicenter study on MR carried out in 11 Spanish hospitals with a pediatric hospitalization unit. It lasted 12 months and included pediatric patients with hemato-oncologic diseases aged between 0 and 18 years. Subjects could be admitted at any time during the course of the study.

Patients who were hospitalized for 24 hours or less, and those for whom a clinical interview (with them or their carer) was not possible, or for whom information about their usual treatment could not be reliably obtained, were excluded from the analysis.

To obtain the required information on the patients' pharmacotherapeutic history (PTH), a review of their hospital and primary care records, as well as of medical and nursing reports from other hospitals, was carried out. A clinical interview was also conducted with the patients and/or their carers.

Once sufficient information on each patient's PTH was obtained, an analysis was made of the potential discrepancies between their usual medication regimen and the medication prescribed to them on admission. A comparison was made between each patient's PTH and the medication prescribed to them on admission, taking into consideration their current clinical situation, the reasons given by the prescribing physician and the indications associated with the prescribed pharmacological treatment.

Discrepancies were classified as justified or unjustified according to the Consensus Document on terminology and classification in medication reconciliation published by the Spanish Society of Hospital Pharmacists (2009)13, the latter being considered as REs potentially responsible for MEs. When a RE was identified, the prescriber was contacted. All such communications were recorded for subsequent analysis.

The variables examined in the study, in addition to patients' demographics and place of origin, included the reason for admission and the unit to which they were admitted; the underlying condition and any drug allergies or intolerances; medications they were taking (patients taking four or more home medications were considered polymedicated); the number of narrow therapeutic index drugs (NTIDs) used; and any discrepancies found, the type of discrepancies and the drug involved.

The data werecollected using the free software REDcap (Research Electronic Database Capture), a web-basedtool for the management, design and coordination of multicenter clinical trials.

Statistical analysis of the data was performed using the SAS® 9.4. statistical package. Quantitative variables were described using descriptive statistical measures such as mean and median. The Shapiro-Wilks, the chi-squared test and Fisher's Exact Test were used as appropriate.

The study was classified as a non-post-authorization study by the Spanish Agency for Medicines and Medical Devices and was approved by the Ethics Committee of the lead institution involved in the study.

MEs are among the most frequent causes of injuries and preventable harm in the health systems of the world over. Patient safety is of upmost importance in clinical practice.MEs can occur at any stage of the drug utilization process with a greater impact in specific environmentslike the inpatient setting. This could be attributed to the locationof severe and acute clinical cases and the application of complex drug regimens. Adverse drug events are more likely to affect young children and elderly patients.

In 2017, the WHO initiated the “Medication without harm” scheme under its third Global Patient Safety Challenge. The program comprised several measures to ensure safe pharmacological practices and reduce the incidence of severe preventable medication-related harm.

Several studies have shown that on-admission MR in adult hemato-oncologic patients is effective in identifying and addressing MEs and problems related to medication.19–21 In particular, Damlien et al.19 found at least one discrepancy in 80% of patients, and Kraus et al.20 reported an incidence of 63.6%. In the current study, at least one discrepancy was found in 61% of patients.

In a study involving144 hemato-oncologic pediatric patients, Schuch et al.22 found a 14% incidence of REs, with 43% of polymedicated patients experienced at least one RE. The higher percentages found in the present study (49% of REs and 68% of polymedicated patients with at least one RE) could be due to the fact that the percentage of polymedicated patients in Schuch et al. was lower compared to these series (36% vs. 55%).

In their study on hospitalized adult hemato-oncologic patients, Moghli et al.23 found a slightly higher incidence of REs than our study in pediatric patients (66.3% vs. 49%). This may be due to the fact that the mean number of drugs used by patients in Moghli et al. was 6.5 as compared with 5.1 in this study. The most common type of RE in Moghli et al.23 was omission, with the majority of errors ocurring in drugs classified under the ATC code A (alimentary tract and metabolism). These findings are consistent with the outcomes of our study.

Son et al.21 identified that the most frequent PIs were related to the treatment duration and to the requirement to add an extra drug (due to the most frequently detected REs in our study, i.e., omission of a drug). Likewise, the most common RE identified by Schuch et al. 22 was the omission of a drug.

Damlien19 and Kraus20 found a correlation between the amount of medication patients habitually use and the occurrence of discrepancies. In our study, we identified a statistically significant correlation between the number of drugs taken by patients at home and the incidence of REs.

The study's most striking revelation was the overwhelming prevalence of homeopathic/phytotherapeutic preparations available over the counter in our sample (99%). This highlights the crucial role that pharmacists play in reviewing the pre-admission treatments of such patients and identifying potential interactions between these products and the prescribed treatments provided during their hospital stay.

The results of this study may be valuable to hospital pharmacists involved in the area of pediatrics, specifically hemato-oncologic pediatrics, as they may help them in the improved selection of polymedicated patients on admission and facilitate the reconciliation of their medication.

One of the strengths of this study is its multicenter design, covering Spain comprehensively and reducingpotential risks from patient managementduring transitions of care across different regions of the country. However, the COVID-19 pandemic presented the main limitation by occasionally hindering both the reconciliation process and patient interviews, resulting in the potential loss of patients.

This study revealed the existence of a significant amount of involuntary discrepancies, which could lead to REs upon admission. Most of these REs related to home medication being omitted from hospital prescriptions. Our findings emphasize the necessity ofimplementing new approaches to medication management during admission to decrease the occurrence of REs.

The performance of similar studies, but including complex pediatric patients suffering from diseases other than cancer, could offer valuable insights in determining whether the results of this analysis can be generalized to the entire pediatric patient population.

This study sheds light on the incidence of on-admission reconciliation errors amongpediatric hemato-oncologic patients. It also investigates the potential variables, either demographic or resulting from the complexity of the treatment, that could be associated to the appearance of such errors. A univariate analysis is presented to determine how each variable may influence the occurrence of REs. The results of the study may guide the development of strategies for selecting and prioritizing patients at risk of REs during care transitions. This would allow pharmacists working with hemato-oncologic patients to incorporate REs into the pharmaceutical care protocol.

Pursuant to Spanish Organic Data Protection Law 3/2018 and Regulation 2016/679 of the European Parliament and of the Council of 27 April 2016, the patients' personal data was protected through a correlative numerical code preceded by the hospital's initials.

Margarita Cuervas-Mons Vendrell participated in the planning and design of the study, as well as in the collection of data, the interpretation of results and the writing of the manuscript.

Dolores Pilar Iturgoyen Fuentes participated in the collection of data, the interpretation of results and in the writing of the manuscript.

Miquel Villaronga Flaque, María José Cabañas Poy, Cecilia M. Fernández-Llamazares, Concha Álvarez Del Vayo, Carmen Gallego Fernández, Cristina Martínez Roca, Yolanda Hernández Gago, Ana García Robles y Beatriz Garrido Corro participated in the collection of data.

All co-authors carried out a critical review of the manuscript, approved the final version and agreed to it being submitted for publication.

None.