Stability of meropenem in portable elastomeric infusion devices: which protocol should be implemented in clinical practice?

Meropenem has an excellent activity against gram-positive and gram-negative bacteria, including multi-resistant microorganisms. Even though meropenem is a great candidate for outpatient parenteral antimicrobial therapy (OPAT), its physicochemical stability is a major challenge. This work aimed to demonstrate the suitability of including meropenem in OPAT by elucidating its physicochemical stability in a range of commonly prescribed concentrations within portable elastomeric infusion devices. Physical and chemical stability were evaluated at two concentrations commonly used in clinical practice (2 and 25 mg/mL), and three temperatures (2°C-8°C, 25°C, and 32°C) using Accufuser portable elastomeric infusion devices. Drug adsorption onto portable elastomeric infusion devices was also determined at the end of the experiment. Meropenem stability significantly decreased at higher temperatures and when higher drug solution concentrations were used. Meropenem solutions at 2 mg/mL kept the drug content above 95% over 24 h at 2°C-8°C but just for 8 h at 25°C. Nevertheless, solutions containing 25 mg/mL of meropenem showed a dramatic decrease in chemical stability after 8 h 2°C-8°C and just after 4 h at 25°C or 32°C. However, physical stability was kept favorable during this period. The drug adsorption on the material of the elastomeric infusion device was below 1%, indicating the suitability of the chosen device. We propose several administration protocols for meropenem in portable elastomeric infusion devices in clinical practice, according to the results obtained in our study. The results obtained in this study open up the possibility of administering meropenem in an OPAT setting despite its short stability.IMPORTANCEAlthough outpatient parenteral antibiotic therapy can be a good approach to treating infections, a lack of data regarding antibiotic stability in portable elastomeric infusion devices restricts its safe and effective use. Actually, meropenem is used for prolonged periods above 24 h, and it is not physicochemically stable, which can compromise efficacy and toxicity. This work is of high importance to show the clinicians the real shelf life of meropenem when administered in portable elastomeric infusion devices. We propose several administration protocols for meropenem in portable elastomeric infusion devices in clinical practice, according to the stability drug results obtained in our study.

Stability of meropenem in portable elastomeric infusion devices: which protocol should be implemented in clinical practice?

IMPORTANCE: Although outpatient parenteral antibiotic therapy can be a good approach to treating infections, a lack of data regarding antibiotic stability in portable elastomeric infusion devices restricts its safe and effective use. Actually, meropenem is used for prolonged periods above 24 h, and it is not physicochemically stable, which can compromise efficacy and toxicity. This work is of high importance to show the clinicians the real shelf life of meropenem when administered in portable elastomeric infusion devices. We propose several administration protocols for meropenem in portable elastomeric infusion devices in clinical practice, according to the stability drug results obtained in our study.

Antibiotic stability in portable elastomeric infusion devices: A systematic review.

PURPOSE: Although outpatient parenteral antibiotic therapy (OPAT) can be a good approach to treatment of infections, a lack of data regarding antibiotic stability in portable elastomeric infusion devices restricts its safe, appropriate, and effective use. The objective of this work was to complete a systematic peer-reviewed analysis of published articles about antibiotic stability in elastomeric infusion devices that provide evidence supporting their use in OPAT. SUMMARY: A systematic review following PRISMA guidelines was conducted in January 2021 to identify published articles about antibiotic stability in portable elastomeric infusion devices. The databases used were PubMed, Embase, Web of Science, and a Cochrane database. A total of 1,615 original studies and conference communications were found. After title, abstract, and full-text review, 33 articles met the inclusion criteria. The data obtained included information about the stability of 30 different antibiotics. To our knowledge, this is the first review to summarize the available published data on the stability of antibiotics in portable elastomeric infusion devices. The results highlight the poor stability of some antibiotics in solution and the variability of the laboratory conditions in the included studies. CONCLUSION: This systematic review can serve as a useful resource for healthcare professionals involved in providing OPAT using portable elastomeric infusion devices. However, further stability studies should be performed, especially high-quality studies simulating real-life time and temperature conditions.

Analysis of adverse drug events as a way to improve cancer patient care.

PURPOSE: To define the signals that a new artificial intelligence (AI) system must emit to improve adverse drug events (ADEs) management in oral antineoplastic agents (OAA). METHODS: A multidisciplinary group of experts in patient safety was set up to define what signals the new AI system must emit to improve ADEs management in OAAs. The baseline data for the new AI system were generated through an observational and ambispective study carried out in a university hospital. All patients who met the inclusion criteria were selected consecutively every working day for 6 months. The ADEs were collected by interview and by the review of health records. The ADEs were categorised according to how they could be detected: patient, analysis, examination. RESULTS: The group defined what signals the AI system must emit to improve ADEs management in OAAs: a signal to educate the patient when the possible ADEs were categorised as patient, a signal as a reminder to request a blood test or a microbiological culture when the possible ADEs were categorised as analysis, and a signal as a reminder for the necessity of a clinical examination when the possible ADEs were categorised as examination. A total of 1652 ADEs were reported in the interviews (ADE-interview) with the pharmacist, and doctors noted 1989 ADEs in the health record (ADE-HR). The most frequent ADEs were identified in the patient category. CONCLUSION: This study opens a new way for better management of ADEs and is the first step in the development of a future technology, which will improve the quality of life of patients.

[Analysis of patient safety in the process of drug prescription in research.] / Análisis de la seguridad del paciente en el proceso de prescripción de medicamentos en investigación.

OBJECTIVE: The increasing complexity of clinical trial protocols and the very nature of investigational drugs increase the likelihood of prescribing errors and require comprehensive control and monitoring of treatments. The aim of this study was to measure and analyze the potential risks of prescribing errors in investigational drugs. METHODS: A prospective, descriptive, and observational study was carried out in a third-level hospital in Madrid, for one month in 2017. Manual prescribing errors (EP) in investigational drugs and potential risks of harm to the patient were analyzed. A descriptive statistical analysis was performed, including the absolute and relative frequency for the variables. RESULTS: A total of 254 medical orders corresponding to 327 lines of treatment and 274 different drugs were reviewed, of which 83% were categorized as "high-risk". Results showed 217 (85.4%) EP within the identification of the medical order and 1,045 (319,6%) in the treatment. The risk level of harm to the patient was high for all EP in patient identification and moderate for all EP in the clinical trial identification. The lines of treatment showed an especially high-risk potential for EP in dosage (25%) and frequency (41%). CONCLUSIONS: The high rate of EP found, along with the high-risk potential these entail, reflects the need for improving the security process when prescribing investigational drugs in our field.

OBJETIVO: La creciente complejidad de los protocolos de ensayo clínico y la propia naturaleza de los medicamentos en investigación aumentan la probabilidad de errores de medicación, a la par que exigen un control y seguimiento exhaustivo de los tratamientos. El objetivo de este artículo fue medir y analizar el riesgo potencial de los errores de prescripción de los medicamentos en investigación. METODOS: Se realizó un estudio prospectivo, descriptivo y observacional en un hospital de tercer nivel de Madrid, durante un mes en 2017. Se analizaron los errores de prescripción (EP) manual de medicamentos en investigación y el riesgo potencial de causar daño al paciente. Se realizó un análisis estadístico descriptivo, incluyendo la frecuencia absoluta y relativa para las variables. RESULTADOS: Se revisaron 254 órdenes médicas correspondientes a 327 líneas de tratamiento y 274 medicamentos distintos, de los cuales el 83% se categorizaron de riesgo alto. Se encontraron 217 (85,4%) EP en la identificación de la orden médica y 1.045 (319,6%) en el tratamiento. El nivel de riesgo de causar daño al paciente fue alto para todos los EP de identificación del paciente y moderado para todos los EP de identificación del ensayo clínico. En las líneas de tratamiento, el riesgo potencial fue alto, principalmente en los EP de dosis (25%) y frecuencia (41%). CONCLUSIONES: El elevado número de EP encontrados, junto con el alto riesgo potencial que supone la mayoría de ellos, refleja la necesidad de mejorar la seguridad del proceso de prescripción de medicamentos en investigación en nuestro entorno.

Grading the potential safety risk of medications used in hospital care / Clasificación de los grupos de medicamentos según su nivel de riesgo en el ámbito hospitalario

Objective: The aim of this study was to stratify medications used in hospital care according to their potential risk. Method: The RAND/UCLA Appropriateness Method was used. Anatomical Therapeutic Chemical subgroups were classified according to their potential risk. A literature search, bulletins, and alerts issued by patient safety organizations were used to identify the potential safety risk of these subgroups. Nine experts in patient/medication safety were selected to score the subgroups for their appropriateness in the classification. Two evaluation rounds were conducted: the first by email and the second by a panel meeting. Results: A total of 298 Anatomical Therapeutic Chemical subgroups were evaluated. They were classified into three scenarios (low, medium, and high risk). In the first round, 266 subgroups were classified as appropriate to the assigned scenario, 32 were classified as uncertain, and none were classified as inappropriate. In the second round, all subgroups were classified as appropriate. The most frequent subgroups in the low-risk scenario belonged to group A "Alimentary tract and metabolism" (44%); the most frequent in the medium-risk scenario belonged to group J "Antiinfectives for systemic use" (32%); and the most frequent in the high-risk scenario belonged to group L "Antineoplastic and immunomodulating agents" (29%) and group N "Nervous system" (26%). Conclusions: Based on the RAND/UCLA appropriateness method, Anatomical Therapeutic Chemical subgroups used in hospital care were classified according to their potential risk (low, medium, or high). These lists can be incorporated into a risk-scoring tool for future patient/medication safety studies (AU)

Objetivo: Estratificar los medicamentos utilizados en el ámbito hospitalario según el riesgo de provocar daño al paciente. Método: Se utilizó la metodología RAND/UCLA para clasificar los subgrupos terapéuticos del código Anatómica, Terapéutica, Química según el riesgo de provocar daño al paciente. Para ello se realizó una revisión de la evidencia disponible en publicaciones, boletines y alertas de organismos de seguridad del paciente. A continuación se seleccionaron nueve expertos en seguridad del paciente/medicamento para evaluar la clasificación de los subgrupos terapéuticos: una primera ronda de evaluación por vía telemática y una segunda ronda en una reunión presencial en la que se presentaron y discutieron los resultados de la primera. Resultados: Se evaluaron 298 subgrupos terapéuticos. Se clasificaron en tres escenarios (riesgo bajo, medio y alto). En la primera ronda se clasificaron 266 subgrupos como adecuados al escenario asignado, 32 subgrupos fueron clasificados como inciertos y ninguno fue clasificado como inapropiado. En la segunda ronda, todos los subgrupos fueron clasificados como adecuados. Los subgrupos más frecuentes en el escenario de riesgo bajo pertenecieron al Grupo A: "Tracto alimentario y metabolismo" (44%), en el de riesgo medio al Grupo J: "Antiinfecciosos para uso sistémico" (32%), y en el de riesgo alto al Grupo L: "Agentes antineoplásicos e inmunomoduladores" (29%) y al Grupo N: "Sistema nervioso" (26%). Conclusiones: La metodología RAND/UCLA ha permitido estratificar los subgrupos utilizados en el ámbito hospitalario según el riesgo potencial de provocar daño al paciente. Esta estratificación puede servir como herramienta para futuros estudios de seguridad en la utilización de medicamentos (AU)

Grading the potential safety risk of medications used in hospital care.

OBJECTIVE: The aim of this study was to stratify medications used in hospital  care according to their potential risk. METHOD: The RAND/UCLA Appropriateness Method was used. Anatomical Therapeutic Chemical subgroups were classified according to their potential risk. A literature search, bulletins, and alerts issued by patient safety organizations were used to identify the potential safety risk of  these subgroups. Nine experts in patient/medication safety were selected to score the subgroups for their appropriateness in the classification. Two evaluation rounds were conducted: the first by email and the second by a  panel meeting. RESULTS: A total of 298 Anatomical Therapeutic Chemical subgroups were  evaluated. They were classified into three scenarios (low, medium, and high  risk). In the first round, 266 subgroups were classified as appropriate to the  assigned scenario, 32 were classified as uncertain, and none were classified as  inappropriate. In the second round, all subgroups were classified as appropriate.  The most frequent subgroups in the low-risk scenario belonged to  group A "Alimentary tract and metabolism" (44%); the most frequent in the  medium-risk scenario belonged to group J "Antiinfectives for systemic use"  (32%); and the most frequent in the high-risk scenario belonged to group L  "Antineoplastic and immunomodulating agents" (29%) and group N "Nervous  system" (26%). CONCLUSIONS: Based on the RAND/UCLA appropriateness method, Anatomical  Therapeutic Chemical subgroups used in hospital care were classified according  to their potential risk (low, medium, or high). These lists can be incorporated  into a risk-scoring tool for future patient/medication safety studies.

Objetivo: Estratificar los medicamentos utilizados en el ámbito hospitalario según el riesgo de provocar daño al paciente.Método: Se utilizó la metodología RAND/UCLA para clasificar los subgrupos terapéuticos del código Anatómica, Terapéutica, Química según el  riesgo de provocar daño al paciente. Para ello se realizó una revisión de la  evidencia disponible en publicaciones, boletines y alertas de organismos de  seguridad del paciente. A continuación se seleccionaron nueve expertos en  seguridad del paciente/medicamento para evaluar la clasificación de los  subgrupos terapéuticos: una primera ronda de evaluación por vía telemática y  una segunda ronda en una reunión presencial en la que se presentaron y  discutieron los resultados de la primera.Resultados: Se evaluaron 298 subgrupos terapéuticos. Se clasificaron en tres  escenarios (riesgo bajo, medio y alto). En la primera ronda se clasificaron 266  subgrupos como adecuados al escenario asignado, 32 subgrupos fueron  clasificados como inciertos y ninguno fue clasificado como inapropiado. En la  segunda ronda, todos los subgrupos fueron clasificados como adecuados. Los  subgrupos más frecuentes en el escenario de riesgo bajo pertenecieron al Grupo  A: "Tracto alimentario y metabolismo" (44%), en el de riesgo medio al Grupo J:  "Antiinfecciosos para uso sistémico" (32%), y en el de riesgo alto al Grupo L:  "Agentes antineoplásicos e inmunomoduladores" (29%) y al Grupo N: "Sistema  nervioso" (26%).Conclusiones: La metodología RAND/UCLA ha permitido estratificar los  subgrupos utilizados en el ámbito hospitalario según el riesgo potencial de  provocar daño al paciente. Esta estratificación puede servir como herramienta  para futuros estudios de seguridad en la utilización de medicamentos.

A continuous usability evaluation of an electronic medication administration record application.

RATIONALE, AIMS, AND OBJECTIVES: The complexity of an electronic medication administration record (eMAR) has been underestimated by most designers in the past. Usability issues, such as poorly designed user application flow in eMAR, are therefore of vital importance, since they can have a negative impact on nursing activities and result in poor outcomes. The purpose of this study was to evaluate the usability of an eMAR application during its development. METHODS: A usability evaluation was conducted during the development of the eMAR application. Two usability methods were used: a heuristic evaluation complemented by usability testing. Each eMAR application version provided by the vendor was evaluated by 2 hospital pharmacists, who applied the heuristic method. They reviewed the eMAR tasks, detected usability problems and their heuristic violations, and rated the severity of the usability problems. Usability testing was used to assess the final application version by observing how 3 nurses interacted with the application. RESULTS: Thirty-four versions were assessed before the eMAR application was considered usable. During the heuristic evaluation, the usability problems decreased from 46 unique usability problems in version 1 (V1) to 9 in version 34 (V34). In V1, usability problems were categorized into 154 heuristic violations, which decreased to 27 in V34. The average severity rating also decreased from major usability problem (2.96) to no problem (0.23). During usability testing, the 3 nurses did not encounter new usability problems. CONCLUSION: A thorough heuristic evaluation is a good method for obtaining a usable eMAR application. This evaluation points key areas for improvement and decreases usability problems and their severity.

Technology-induced errors associated with computerized provider order entry software for older patients.

Background The introduction of new technologies in the prescribing process has seen the emergence of new types of medication errors. Objective To determine the prevalence and consequences of technology-induced prescription errors associated with a computerized provider order entry (CPOE) system in hospitalized older patients. Setting Patients 65 years or older admitted to the Departments of Internal Medicine, General Surgery, and Vascular Surgery of a tertiary hospital. Method Prospective observational 6-month study. Technology-induced errors were classified according to various taxonomies. Interrater reliability was measured. Consequences were assessed by interviewing patients and healthcare providers and classified according to their severity. Main outcome measure Prevalence of technology-induced errors. Results A total of 117 patients were included and 107 technology-induced errors were recorded. The prevalence of these errors was 3.65%. Half of the errors were clinical errors (n = 54) and the majority of these were classified as wrong dose, wrong strength, or wrong formulation. Clinical errors were 9 times more likely to be more severe than procedural errors (14.8 vs 1.9%; OR 9.04, 95% CI 1.09-75.07). Most of the errors did not reach the patient. Almost all errors were related to human-machine interactions due to wrong (n = 61) or partial (n = 41) entries. Conclusion Technology-induced errors are common and intrinsic to the implementation of new technologies such as CPOE. The majority of errors appear to be related to human-machine interactions and are of low severity. Prospective trials should be conducted to analyse in detail the way these errors occur and to establish strategies to solve them and increase patient safety.

Effect of an electronic medication administration record application on patient safety.

RATIONALE, AIMS, AND OBJECTIVES: To evaluate the effect of an electronic medication administration record (eMAR) application on the rate of medication errors in medication administration recording (ME-MAR). METHODS: A before-and-after, quasiexperimental study was conducted in a university hospital that implemented the eMAR application in March 2014. Data collection was conducted in April 2012 (pre-) and June 2014 (post-) by two pharmacists. The ME-MARs were analysed by the staff involved to identify their cause. The two pharmacists independently classified the ME-MARs. In the case of disagreement, a research team examined the ME-MARs and categorized them by consensus. Three classifications were used: A classic medication error taxonomy and 2 technology-induced error taxonomies. RESULTS: The pharmacists analysed 2835 (pre-) and 2621 (post-) medication administration records (MAR), respectively. Overall, the ME-MAR rate decreased from 48.0% (pre-) to 36.9% (post-) (P < .05). The same types of ME-MAR were observed in both phases except for "MAR with incomplete information," which was not observed in the postimplementation phase. In both phases, the most frequent ME-MAR was "MAR at the wrong time" (MAR before or after medication administration) (31.6% vs 30.2%). The main cause of ME-MARs in both phases was the failure to follow work procedures. The potential future risk of ME-MARs significantly decreased after the eMAR implementation (P < .05). All ME-MARs were "use errors" because of human factors. New ME-MARs (1.24%; n = 12) were observed in the postimplementation phase. CONCLUSION: Use of the eMAR application significantly reduces the rate of ME-MAR and their potential risk. The main cause of ME-MAR was the failure to follow work procedures.

Potential future risk of errors in medication administration recording.

RATIONALE, AIMS AND OBJECTIVES: The aim of this study is to adapt and assess the interrater reliability of a potential future risk matrix for medication errors in medication administration recording (ME-MAR). METHODS: The study was carried out in a teaching hospital. It was conducted in two phases. In the first phase, a consensus method was used in order to adapt the potential future risk matrix published by the National Patient Safety and Otero et al. to the ME-MAR. The consensus method consisted in a nominal group formed by four pharmacists. In the second phase, a multidisciplinary group of experts in patient safety assessed the reliability of the adapted matrix. Five raters evaluated 100 ME-MAR. Its reliability was evaluated using the kappa statistic. RESULTS: In the first phase, two meetings were necessary until consensus was reached to adapt the potential future risk matrix to the ME-MAR. For this purpose, the two following categories were defined: likelihood of ME-MAR's recurrence and most likely consequences of ME-MAR. The definition of each grade of likelihood of recurrence was based on the incidence of ME-MAR from an unpublished study carried out in our hospital. In order to determine the most likely consequences of ME-MAR, a two-dimensional matrix was designed, with severity per type of ME-MAR on one axis and the class of medication on the other. In the second phase, the reliability of the matrix was tested. The overall interrater agreement for the five raters was substantial at 0.68 (Confidence interval 95% 0.60-0.76). CONCLUSION: The adapted matrix of potential future risk to ME-MAR is reliable and can serve as a guide for future studies.