The inability to belch: a neglected disease in the era of high-resolution esophageal manometry.

Retrograde upper esophageal sphincter dysfunction (R-UESD) is characterized by the inability to belch. Evidence of using high-resolution manometry (HRM) in diagnosing R-UESD has emerged in recent years. We describe the clinical picture and HRM patterns of two patients with R-UESD. Case 1: A 23-year-old female presented with a two-year complaint of inability to belch. We performed HRM with a belch provocation test for which the patient drank 500 ml of carbonated water. The study revealed increased esophageal pressure, an absence of UES relaxation and secondary peristalsis once the patient mentioned the need to belch. Case 2: A 21-year-old male presented to our medical office with a history of an incapacity to belch during the last three years. We performed HRM with a belch provocation test. During the study, he reported an incapacity to belch and his symptoms coincided with increased esophageal pressure, an absence of UES relaxation, and secondary peristalsis. Retrograde upper esophageal sphincter dysfunction is a rare condition characterized by a lack of UES relaxation during esophageal distension. The incapacity to belch is the hallmark of the disease. We encourage the use of HRM, looking for an increase in esophageal pressure to the level of gastric pressure, failure of UES relaxation with consequently no venting of air across the UES, and secondary peristalsis. In conclusion, diverse R-UESD clinical presentations represent a diagnostic challenge for physicians. This case series highlights the need to actively search for typical HRM findings when encountering patients referring an incapacity to belch.

Endoscopic stent placement after spontaneous esophageal perforation associated with chemoradiotherapy for esophageal cancer.

A 38-year-old male with established diagnosis of stage IV squamous cell carcinoma of the esophagus treated with chemoradiotherapy (25 sessions of 50 Gy), presented with acute aphagia, thoracic pain, productive cough, and mild hemoptysis. Upon physical examination the right hemithorax presented with crepitations. An initial CT scan showed an esophageal perforation. An upper endoscopy was performed, visualizing the esophageal perforation in the mid third of the esophagus at 26 cm of the dental arcade. It was possible to bypass and intubate the stomach, enabling the placement of a guide wire under endoscopic visualization. Afterwards, a partially covered, self-expandable, metal stent (Wallflex esophageal stent 10 cm/18/23; Boston Scientific) was placed in the esophagus restoring continuity, visualized by fluoroscopy.

Pyogenic granuloma of the terminal ileum diagnosed by colonoscopy: the relevance of ileocecal valve intubation.

Pyogenic granuloma is a benign vascular lesion that is most frequently found in the epidermis or mucosa of the oral cavity. Its finding in the ileum is rare, there are only a few case reports. In most reported cases, diagnosis is made with capsule endoscopy or double-balloon enteroscopy. We present a case of a lesion in the ileum, approximately 15 cm from the ileocecal valve, documented by colonoscopy.

External evaluation of population pharmacokinetic models of imatinib in adults diagnosed with chronic myeloid leukaemia.

AIMS: Imatinib is considered the standard first-line treatment in newly diagnosed patients with chronic-phase myeloid leukaemia (CML). Several imatinib population pharmacokinetic (popPK) models have been developed. However, their predictive performance has not been well established when extrapolated to different populations. Therefore, this study aimed to perform an external evaluation of available imatinib popPK models developed mainly in adult patients, and to evaluate the improvement in individual model-based predictions through Bayesian forecasting computed by each model at different treatment occasions. METHODS: A literature review was conducted through PubMed and Scopus to identify popPK models. Therapeutic drug monitoring data collected in adult CML patients treated with imatinib was used for external evaluation, including prediction- and simulated-based diagnostics together with Bayesian forecasting analysis. RESULTS: Fourteen imatinib popPK studies were included for model-performance evaluation. A total of 99 imatinib samples were collected from 48 adult CML patients undergoing imatinib treatment with a minimum of one plasma concentration measured at steady-state between January 2016 and December 2020. The model proposed by Petain et al showed the best performance concerning prediction-based diagnostics in the studied population. Bayesian forecasting demonstrated a significant improvement in predictive performance at the second visit. Inter-occasion variability contributed to reducing bias and improving individual model-based predictions. CONCLUSIONS: Imatinib popPK studies developed in Caucasian subjects including α1-acid glycoprotein showed the best model performance in terms of overall bias and precision. Moreover, two imatinib samples from different visits appear sufficient to reach an adequate model-based individual prediction performance trough Bayesian forecasting.

[Translated article] Analysis of the degree of implementation of medication error prevention practices in Spanish hospitals (2022).

OBJECTIVE: To assess the degree of implementation of medication error prevention practices in Spanish hospitals. METHOD: Descriptive multicenter study of the degree of implementation of the safety practices included in the "Medication use-system safety self-assessment for hospitals. Version. II". Spanish hospitals that completed the questionnaire between October, 2021 and September, 2022 participated. The survey contains 265 items for evaluation grouped into 10 key elements. Mean score and mean percentages based on the maximum possible values for the overall survey, for the key elements, and for each individual item of evaluation were calculated. The results were compared with those of the previous 2011 study. RESULTS: A total of 131 hospitals from 15 autonomous regions participated in the study. The mean score of the overall questionnaire in all hospitals was 898.2 (57.4% of the maximum possible score). No differences were found according to dependency, size, or type of hospital, either in the overall questionnaire or in the key elements. The lowest values were found for key elements VIII, I and VI, on competence and training of health professionals in safety practices (45.1%), availability and accessibility of essential information on patients (48%), and devices for administering drugs (52.3%). With respect to 2011, significant increases were found both in the overall questionnaire and in the key elements, except V and VII, referring to standardization, storage, and distribution of medications, and environmental factors and human resources. Several evaluation items on the safe management of high-risk drugs, medication reconciliation, incorporation of clinical pharmacists into the healthcare teams, and implementation of technologies that allow full traceability throughout the medication system, showed low percentages. CONCLUSIONS: There has been appreciable progress in the degree of implementation of some medication error prevention practices in Spanish hospitals, but many proven efficacy practices recommended by the World Health Organization and safety organizations are still poorly implemented. The information obtained can be useful for prioritizing the practices to be addressed and as a new baseline for monitoring progress.

Analysis of the degree of implementation of medication error prevention practices in Spanish hospitals (2022). / Análisis del grado de implantación de las prácticas de prevención de errores de medicación en los hospitales españoles (2022).

OBJECTIVE: To assess the degree of implementation of medication error prevention practices in Spanish hospitals. METHOD: Descriptive multicenter study of the degree of implementation of the safety practices included in the "Medication use-system safety self-assessment for hospitals. Version. II". Spanish hospitals that completed the questionnaire between October/2021 and September/2022 participated. The survey contains 265 items for evaluation grouped into 10 key elements. Mean score and mean percentages based on the maximum possible values for the overall survey, for the key elements and for each individual item of evaluation were calculated. The results were compared with those of the previous 2011 study. RESULTS: A total of 131 hospitals from 15 autonomous regions participated in the study. The mean score of the overall questionnaire in all hospitals was 898.2 (57.4% of the maximum possible score). No differences were found according to dependency, size or type of hospital, either in the overall questionnaire or in the key elements. The lowest values were found for key elements 8, 1 and 6, on competence and training of health professionals in safety practices (45.1%), availability and accessibility of essential information on patients (48%), and devices for administering drugs (52.3%). With respect to 2011, significant increases were found both in the overall questionnaire and in the key elements, except 5 and 7, referring to standardization, storage and distribution of medications, and environmental factors and human resources. Several evaluation items on the safe management of high-risk drugs, medication reconciliation, incorporation of clinical pharmacists into the healthcare teams and implementation of technologies that allow full traceability throughout the medication system, showed low percentages CONCLUSIONS: There has been appreciable progress in the degree of implementation of some medication error prevention practices in Spanish hospitals, but many proven efficacy practices recommended by the World Health Organization and safety organizations are still poorly implemented. The information obtained can be useful for prioritizing the practices to be addressed and as a new baseline for monitoring progress.

Multicentre Study Into the Use of Polyethylene Glycol With Electrolytes Over at Least 6 Months to Treat Constipation in Paediatric Populations.

Background: Constipation is a common clinical problem in children, for which the first-line therapeutic options are osmotic laxatives, mainly polyethylene glycol (PEG). These treatments are often prescribed for short or limited periods, with progressive treatment withdrawal often resulting in relapses. However, there are a few studies into the long-term use (≥6 months) of PEG 3350 with electrolytes (PEG+E) in terms of the patients' clinical evolution. Objectives: To assess bowel movement and other relevant symptoms in children with constipation receiving PEG+E (≥6 months), as well as parent/caregiver satisfaction with this treatment. Methods: A retrospective, observational, descriptive, longitudinal, and multicentre study was carried out on 74 children diagnosed with functional constipation (ROME IV criteria) who had received PEG+E (≥6 months). Bowel control was assessed using the Bristol stool scale, and the parent's/caregiver's perception of the treatment was also evaluated employing a nonvalidated questionnaire. Results: Children with an average duration of constipation >1 year experienced a significant improvement in bowel movements and stool consistency when using PEG+E. The mean duration of use was 18.6 (±13.4) months, without the need to adjust the dose for weight. All clinical symptoms improved significantly except bloating, and all the parents/caregivers confirmed these clinical improvements. Conclusions: Children treated with PEG+E (≥6 months) normalised their bowel movements, improving the clinical symptoms related to constipation in the absence of serious advert events or the need for dosage adjustments due to weight gain. Parents/caregivers reported good satisfaction with PEG+E treatment.

Population Pharmacokinetics of Valproic Acid in Pediatric and Adult Caucasian Patients.

(1) Background: The aim of this study was to explore the valproic acid (VPA) pharmacokinetic characteristics in a large population of pediatric and adult Caucasian patients and to establish a robust population pharmacokinetic (PopPK) model. (2) Methods: A total of 2527 serum VPA samples collected from 1204 patients included in a therapeutic drug monitoring program were retrospectively analyzed. Patients were randomly assigned to either a model development group or an external evaluation group. PopPK analysis was performed on 1751 samples from 776 patients with NONMEM using a nonlinear mixed-effect modelling approach. The influence of demographic, anthropometric, treatment and comedication variables on the apparent clearance (CL/F) of VPA was studied. The bootstrap method was used to evaluate the final model internally. External evaluation was carried out using 776 VPA serum samples from 368 patients. (3) Results: A one-compartment model with first-order absorption and elimination successfully described the data. The final model included total body weight, age and comedication with phenytoin, phenobarbital and carbamazepine with a significant impact on VPA elimination. Internal and external evaluations demonstrated the good predictability of the model. (4) Conclusions: A PopPK model of VPA in Caucasian patients was successfully established, which will be helpful for model-informed precision dosing approaches in clinical patient care.

Long-term effectiveness and pharmacokinetics of the infliximab biosimilar CT-P13 after switching from the originator during the treatment of inflammatory bowel disease.

OBJECTIVE: Switching patients from the originator infliximab to a biosimilar is a measure to expand access to treatments and counteract its negative impact on healthcare budgets. However, industry-independent long-term studies on the effect of switching in real life to support the lack of switch-related problems in inflammatory bowel disease (IBD) patients are sparse, as are studies addressing infliximab pharmacokinetic behaviour. The objectives were to investigate the effectiveness and the pharmacokinetics of CT-P13 after switching from originator infliximab in a real-world population of IBD patients with a follow-up of 2 years. METHOD: Prospective, single-centre, observational 2 year study conducted in IBD adult patients with stable disease treated with the originator infliximab who were switched to CT-P13. Four time points were defined for follow-up: prior to the switch, 4-8 weeks after the switch, 8 months later, and 2 years later. Outcome measures were the proportion of patients with clinical, endoscopic and biochemical remission, and changes in biochemical inflammation markers (albumin, C-reactive protein, faecal calprotectin) and infliximab clearance. RESULTS: 42 IBD patients were switched, of which 36 (85.7%) remained on CT-P13 throughout the 2 year study period. Only two patients discontinued CT-P13 due to loss of response. The proportion of patients who displayed clinical, endoscopic and biochemical remission were unchanged during the follow-up (p<0.05) and no statistically significant changes were observed in the biochemical markers of disease activity. The median (IQR) clearance estimated for the infliximab originator before the change was 0.364 (0.321-0.415) L/day, and for the CT-P13 biosimilar it was 0.361 (0.323-0.415) L/day 4-8 weeks after the change, and 0.370 (0.334-0.419) L/day 2 years after (p=0.395). CONCLUSION: Switching from originator infliximab to biosimilar CT-P13 did not affect the long-term clinical outcomes or the pharmacokinetic behaviour. This information provides the clinician more evidence for the success of switching and supports non-medical switching in adult IBD patients.

Population pharmacokinetics of a posaconazole tablet formulation in transplant adult allogeneic stem cell recipients.

BACKGROUND: Posaconazole is an antifungal agent extensively used as a prophylaxis for invasive fungal infections (IFIs) in allogeneic stem cell transplant (SCT) recipients. Low posaconazole concentrations have been associated with reduced clinical response. The aim of this study was to develop a population pharmacokinetic (popPK) model of a posaconazole tablet formulation in allogeneic SCT adult recipients for supporting model-informed precision dosing (MIPD). MATERIALS AND METHOD: Prospective observational study performed in adult allogeneic SCT recipients receiving posaconazole as prophylaxis for IFIs and followed up by a therapeutic drug monitoring (TDM) program. Posaconazole plasma concentrations were quantified using an ultra-high-performance liquid chromatography (UPLC) with UV detector. A popPK model was developed using NONMEM v.7.4.0. Deterministic and stochastic simulations were carried out with the final model to evaluate the differences across physiological variables with impact on drug exposure. RESULTS: A one-compartment model with sequential absorption (zero and first order) and first order elimination described adequately 55 posaconazole concentrations from 36 patients. Higher doses of posaconazole were found to be required by males and patients with lower values of total serum proteins. A nomogram to estimate the posaconazole daily dose based on pharmacokinetic/pharmacodynamic (PKPD) criterion for males and females for different values of total proteins was developed. CONCLUSIONS: Gender and total serum proteins have been identified as covariates influencing posaconazole CL/F in adult allogeneic SCT recipients receiving the delay-released tablet formulation. Additional studies are required to better characterize the absorption of posaconazole and implications on dosage recommendations together with potential safety concerns.

Time to review how injectable medicines are prepared and administered in European hospitals.

It has been known, for decades, that the use of injectable medicines in European hospitals has been associated with frequent medication errors, some of which cause preventable severe harms and deaths. There  have been national and European inquiries and reports concerning  improving patient safety by recommending greater use of pharmacy  aseptic preparation services and provision of ready-to administer  injectables, which have not been widely implemented.In England experience of treating patients with COVID-19 infections has  brought into focus other benefits of significantly extending pharmacy aseptic preparation services. These benefits include saving  nursing time, having systems in place which have resilience and capacity,  reducing variation in practice, improving clinical staff and patient  experience, and enabling more injectable medicines to be administered to  patients at home. It has also been recognised that more action is required  to standardise policies and procedures for injectable medicines and  mplement the use of smart infusion devices with dose error reduction  software, to help minimise drug administration errors.Hospital pharmacists have a key role in developing these services to bring  European hospitals more in line with those provided by hospital pharmacies in North America.

Desde hace décadas se conoce que el uso de los medicamentos  nyectables en los hospitales europeos se encuentra asociado a numerosos  errores de medicación, algunos de los cuales provocan daños graves y  muertes prevenibles. Se han publicado investigaciones e informes  nacionales y europeos sobre la mejora de la seguridad del paciente que  recomiendan una mayor utilización de las unidades de preparación  aséptica de los servicios de farmacia y la provisión de los medicamentos  inyectables listos para su administración, recomendaciones que apenas se  han implementado.En Inglaterra, la experiencia de tratar a los pacientes con infección por  COVID-19 ha puesto de manifiesto otros beneficios que conlleva la ampliación de las unidades de preparación aséptica de los servicios de farmacia. Estos beneficios incluyen ahorrar tiempo de enfermería,  disponer de sistemas con mayor resiliencia y capacidad, reducir la  variabilidad en la práctica, mejorar la satisfacción del personal clínico y del paciente, y facilitar la administración de más medicamentos inyectables a  los pacientes en sus domicilios. También se ha reconocido que se precisan  actuaciones dirigidas a estandarizar las directrices y procedimientos de  utilización de los medicamentos inyectables e implementar el uso de  dispositivos de infusión inteligentes con software de reducción de errores  de dosis, con el fin de minimizar los errores en la administración de estos  medicamentos. Los farmacéuticos de hospital tienen un papel clave en el desarrollo de  stas actividades para que los servicios que prestan las farmacias  hospitalarias europeas estén más en consonancia con los que se  proporcionan en Norteamérica.

Value of skin tests for managing allergic hypersensitivity reactions to platinum compounds.

Background Platinum-based therapy continues to be one of the pillars of the treatment of different types of cancer. However, many times the responsible clinician renounces its use after the appearance of a hypersensitivity reaction. Objective To assess the value of skin tests (ST) in clinical practice to address the treatment of patients with suspicion of immediate hypersensitivity reactions (HSRs) to platinum compounds. Method Single-center retrospective study of 3 years. Adult patients treated with any platinum compound who experienced HSR symptoms and for whom an oncologist requested ST, were included. ST with cisplatin, carboplatin and oxaliplatin were performed. Results Twenty-two patients were included. ST were positive in 12 patients (54.5%), of which 4 (33%) presented cross-reactivity to another platinum compound. Fifteen patients continued platinum-based chemotherapy: 9 patients with positive ST (4 continued by desensitization and 5 with another platinum compound) and 6 patients with negative ST, of which 1 repeated an HSR. A NPV of 0.91 was calculated. Conclusion ST helped physicians identify patients most susceptible to platinum derivative allergies and resume platinum-based therapy in many patients for whom no suitable therapeutic alternative was clinically acceptable.

Validating a Trigger Tool for Detecting Adverse Drug Events in Elderly Patients With Multimorbidity (TRIGGER-CHRON).

PURPOSE: The aims of the study were to evaluate the performance of an initial list developed to detect adverse drug events (ADEs) in elderly patients with multimorbidity in clinical practice, to explore the possibility of shortening the list, and to use this tool to study the incidence and characteristics of the ADEs among this population. METHODS: This observational study was conducted at 12 Spanish hospitals. A random sample of five charts from each hospital was selected weekly for retrospective review for a 12-week period. We included patients aged 65 years and older with multimorbidity, hospitalized more than 48 hours. Adverse drug events were detected using a list of 51 triggers previously selected by an expert panel by means of a modified Delphi method. The number of triggers identified and ADEs detected were recorded. The severity and preventability of the ADEs were evaluated. The positive predictive value (PPV) of each trigger was calculated and used to select the most efficient triggers. RESULTS: In 720 charts reviewed, 1430 positive triggers were identified that led to detect 215 ADEs in 178 patients (24.7%), of which 13% were serious. One hundred nineteen ADEs (55.3%) were preventable and mainly related to inadequate treatment monitoring and prescribing errors. Triggers with a PPV of 5% or less were eliminated, resulting in a final list of 32 triggers (TRIGGER-CHRON) with a PPV of 22.1%, which accounted for 98.9% of all ADEs detected and 98.6% of the preventable ADEs. CONCLUSIONS: The shorter final validated TRIGGER-CHRON tool is an efficient list for identifying ADEs in elderly patients with multimorbidity, detecting ADEs in one-fourth of hospitalized patients in internal medicine or geriatric units.

Development of a Trigger Tool to Identify Adverse Drug Events in Elderly Patients With Multimorbidity.

PURPOSE: Elderly patients with multimorbidity are especially vulnerable to adverse drug events (ADEs) and had high prevalence rates. Identifying ADEs is essential for enabling timely interventions that can mitigate the adverse events detected and for developing targeted strategies to prevent their occurrence as well as to monitor implementation. The aim of this study was to develop a set with appropriate triggers for detecting potential ADEs in elderly patients with multimorbidity. METHODS: A modified Delphi methodology was used to reach consensus. Existing triggers for detecting ADEs in adult patients were identified from a literature search in several databases (EMBASE, MEDLINE, Web of Science, Centre for Reviews and Dissemination, and Cochrane Library) and from Institute for Healthcare Improvement published lists. Twelve experts in patient/medication safety or in chronic diseases scored candidate triggers for appropriateness according to 3 criteria (evidence, usefulness for elderly patients, and feasibility of implementation in clinical practice). RESULTS: Seventy-two triggers were initially selected to be evaluated. The final set includes a total of 51 triggers for which the panelists who completed the 2 rounds of evaluation reached agreement. These triggers were organized into 5 modules: 11 as care module triggers, 10 as antidotes/treatment, 11 medication concentrations, 18 abnormal laboratory values, and 1 as emergency department trigger. CONCLUSIONS: A set of triggers for detecting ADEs in elderly patients with multimorbidity have been developed, following the consensus of a panel of experts. Subsequent validation in clinical practice is needed to confirm the accuracy and efficiency of these triggers for this population.

Utility of a trigger tool (TRIGGER-CHRON) to detect adverse events associated with high-alert medications in patients with multimorbidity.

OBJECTIVE: To determine the utility of a tool (TRIGGER-CHRON) for identifying adverse drug events (ADEs) associated with the administration of high-alert medications in elderly patients with multimorbidity and to determine the medications most frequently implicated. METHODS: A retrospective observational study was conducted at 12 Spanish hospitals. A random sample of five medical records from each hospital was selected weekly for review over a 12-week period. We included patients aged 65 and over with multimorbidities, hospitalised for >48 hours. ADEs detected by the 32 TRIGGER-CHRON signals and caused by high-alert medications included on the Spanish HAMC list for chronic patients were selected for analysis. Triggers identified and ADEs detected were recorded. The severity and preventability of the ADEs were evaluated. The positive predictive value (PPV) of each trigger was calculated. RESULTS: On 720 charts reviewed, 908 positive triggers were identified that led to the detection of 158 ADEs caused by at least one high-alert medication on the HAMC list. These ADEs occurred in 139 patients (prevalence 19.3/100 admissions). The majority of ADEs were mild and 59.5% were deemed preventable. The drugs most frequently associated with ADEs were corticosteroids, loop diuretics, opioid analgesics and oral anticoagulants. Fifteen triggers had PPVs ≥20%. Six triggers (serum glucose >110 mg/dL, abrupt cessation of medication, oversedation/lethargy, hypotension, adverse reaction recorded and constipation) accounted for 69.8% of the ADEs identified. CONCLUSIONS: Applying the TRIGGER-CHRON to hospitalised patients with multimorbidity in 12 Spanish centres allowed detection of one adverse event caused by a high-alert drug for every four patients, which were preventable in a large proportion of patients. This confirms the need to establish interventions that reduce harm with these medications. We believe that TRIGGER-CHRON can be a useful tool to measure this harm and to determine the effects of medication safety improvement programmes as they are implemented.

Relationship between vedolizumab serum concentrations in the induction phase and early and sustained response in the first year of treatment in patients with ulcerative colitis.

OBJECTIVE: Evidence on the usefulness of proactive monitoring of vedolizumab serum concentrations during the induction phase of treatment is limited. The objective of our study was to evaluate the effectiveness of measuring such concentrations during this phase in predicting response to  treatment in patients with ulcerative colitis with a view to determining whether  patients would benefit from early monitoring of  edolizumab serum concentrations. METHOD: This was a prospective descriptive study carried out at three public  general hospitals. It included adult patients with ulcerative colitis who were  initiated on vedolizumab at the participating hospitals from June 2019 to June  2020. Vedolizumab serum concentrations were determined  at weeks 6 and 14.  Response to treatment was biologically, clinically, and endoscopically  evaluated at weeks 6, 14, and 52. An analysis was made of the relationship  between vedolizumab serum concentrations at week 6 and early response to  treatment, and of the relationship between the vedolizumab serum  concentrations at weeks 6 and 14 and persistent response at one year. RESULTS: A total of 45 patients were included of whom 22 (49%) were considered non-responsive after one year and required intensification of treatment. The median (interquartile range) vedolizumab serum  oncentrations obtained at 6 weeks was higher in patients who obtained an  early response and in those who maintained the response at one year than  in  those who did not respond to vedolizumab [27.4 (19.0-40.8) µg/mL vs 15.6  (13.4-28.5) µg/mL; p = 0.018] and [29.9 (19.2-43.2) µg/mL vs 18.2 (15.4- 26.9) µg/mL; p = 0.022] respectively. Vedolizumab serum concentrations ≥  17.3 µg/mL at week 6 were predictive of a good early response, and  edolizumab serum concentrations ≥ 26.1 µg/mL at week 6 predicted a  sustained response at one year. No relationship was found between  edolizumab serum concentrations at week 14 and a sustained response. CONCLUSIONS: We observed a relationship between vedolizumab serum concentrations determined at week 6, and early and maintained  esponse to vedolizumab therapy in patients with ulcerative colitis, which  supports early drug monitoring during the induction phase to individualize  treatment and increase effectiveness.

OBJETIVO: La evidencia sobre la utilidad de la monitorización proactiva de las  concentraciones séricas de vedolizumab en la fase de inducción del tratamiento es limitada. El objetivo del estudio ha sido evaluar la capacidad de las concentraciones séricas de vedolizumab determinadas en esta fase para predecir la respuesta al tratamiento en pacientes con colitis ulcerosa, con  el fin de establecer si los pacientes se beneficiarían clínicamente de una  monitorización precoz.Método: Estudio descriptivo, prospectivo, realizado en tres hospitales generales públicos. Incluyó a los pacientes adultos con colitis  ulcerosa, que iniciaron tratamiento con vedolizumab en los centros  participantes desde junio de 2019 a junio de 2020. Se determinaron las  concentraciones séricas de vedolizumab en las semanas 6 y 14 de tratamiento.  La respuesta bioquímica, clínica y endoscópica se evaluó en las  semanas 6, 14 y 52. Se estudió la relación de las concentraciones séricas de  vedolizumab determinadas en la semana 6 con la respuesta temprana al  tratamiento, así como la relación de las concentraciones séricas de  vedolizumab en las semanas 6 y 14 con la persistencia de respuesta al año de  tratamiento. RESULTADOS: Se incluyeron 45 pacientes, de los que 22 (49%) se consideraron no respondedores al cabo de un año y necesitaron intensificar el  tratamiento. Las medianas (rango intercuartílico) de las concentraciones séricas de vedolizumab en la semana 6 fueron superiores,  tanto en los pacientes que presentaron respuesta temprana como en los que  mantuvieron respuesta al cabo de un año, comparadas con las de los pacientes que no respondieron a vedolizumab [27,4 (19,0-40,8) µg/ml vs  15,6 (13,4­28,5) µg/ml; p = 0,018] y [29,9 (19,2-43,2) µg/ml vs 18,2  (15,4­26,9) µg/ml; p = 0,022], respectivamente. Las concentraciones séricas  de vedolizumab ≥ 17,3 µg/ml en la semana 6 predijeron una buena respuesta  temprana, y concentraciones séricas de vedolizumab ≥ 26,1 µg/ml en la  emana 6 predijeron una respuesta mantenida al cabo de un año. No se  encontró relación entre las concentraciones séricas de vedolizumab en la  semana 14 y la respuesta mantenida. CONCLUSIONES: Se ha observado una relación entre las concentraciones séricas  de vedolizumab determinadas en la semana 6 y la  respuesta temprana y mantenida a la terapia en pacientes con colitis ulcerosa,  lo que avala la monitorización precoz durante la fase de inducción, para individualizar el tratamiento y aumentar su eficacia.

Estudio multicéntrico de la incidencia y evitabilidad de los incidentes por medicamentos en pacientes que acuden a los servicios de urgencias pediátricas.

Objetivo: Determinar la incidencia, gravedad y evitabilidad de los  incidentes por medicamentos detectados en los pacientes que acuden a los servicios de urgencias pediátricas, e identificar los grupos de edad de mayor riesgo y los medicamentos implicados.Método: Estudio multicéntrico observacional prospectivo, realizado entre  marzo y junio de 2017, en pacientes entre 0 y 16 años que acudieron a los servicios de urgencias pediátricas de ocho hospitales públicos españoles. Se recogieron tres tipos de incidentes: eventos adversos por medicamentos, errores de medicación e intoxicaciones accidentales. Los incidentes se caracterizaron atendiendo a su gravedad, evitabilidad, grupos de edad afectados y medicamentos implicados.Resultados: Durante el periodo de estudio se registraron 99.797 visitas a los servicios de urgencias pediátricas y se recogieron 334 incidentes por medicamentos en 334 pacientes, de los cuales el 52,4% fueron varones, con una media de edad de 47,1 ± 44,4 meses. La incidencia de pacientes  con incidentes fue del 0,3%. Del total de incidentes, 264 (79%) fueron considerados prevenibles y 158 (47,3%) produjeron daño a los pacientes. Los incidentes detectados fueron 144 (43,1%) eventos adversos por medicamentos, 218 (65,2%) errores de medicación (74 de ellos errores con daño, que se incluyen asimismo como eventos adversos prevenibles) y 46 (13,7%) intoxicaciones accidentales. Los preescolares (edad: 1-5 años) presentaron el 60,8% de los incidentes, siendo también el grupo de edad con un mayor porcentaje de incidentes prevenibles (64%). Un total de 351 medicamentos estuvieron implicados en los incidentes y pertenecieron mayoritariamente a tres grupos terapéuticos: antiinfecciosos de uso sistémico (171; 48,7%), sistema nervioso (66; 18,8%) y sistema respiratorio (41; 11,7%).Conclusiones: La incidencia de incidentes por medicamentos en los pacientes pediátricos que acudieron a servicios de urgencias fue inferior a la referida en pacientes adultos, si bien prácticamente la mitad de los incidentes detectados causaron daños a los pacientes. Los niños preescolares (1-5 años) fueron identificados como el grupo de edad con mayor riesgo. Los incidentes registrados estuvieron causados por un número reducido de medicamentos. Un elevado porcentaje de los incidentes fueron prevenibles, lo que confirma la imperiosa necesidad de implementar medidas de prevención de incidentes en esta población.

Objetivo: Determinar la incidencia, gravedad y evitabilidad de los  incidentes por medicamentos detectados en los pacientes que acuden a los servicios de urgencias pediátricas, e identificar los grupos de edad de mayor riesgo y los medicamentos implicados.Método: Estudio multicéntrico observacional prospectivo, realizado entre  marzo y junio de 2017, en pacientes entre 0 y 16 años que acudieron a los servicios de urgencias pediátricas de ocho hospitales públicos españoles. Se recogieron tres tipos de incidentes: eventos adversos por medicamentos, errores de medicación e intoxicaciones accidentales. Los incidentes se caracterizaron atendiendo a su gravedad, evitabilidad, grupos de edad afectados y medicamentos implicados.Resultados: Durante el periodo de estudio se registraron 99.797 visitas a los servicios de urgencias pediátricas y se recogieron 334 incidentes por medicamentos en 334 pacientes, de los cuales el 52,4% fueron varones, con una media de edad de 47,1 ± 44,4 meses. La incidencia de pacientes  con incidentes fue del 0,3%. Del total de incidentes, 264 (79%) fueron considerados prevenibles y 158 (47,3%) produjeron daño a los pacientes. Los incidentes detectados fueron 144 (43,1%) eventos adversos por medicamentos, 218 (65,2%) errores de medicación (74 de ellos errores con daño, que se incluyen asimismo como eventos adversos prevenibles) y 46 (13,7%) intoxicaciones accidentales. Los preescolares (edad: 1-5 años) presentaron el 60,8% de los incidentes, siendo también el grupo de edad con un mayor porcentaje de incidentes prevenibles (64%). Un total de 351 medicamentos estuvieron implicados en los incidentes y pertenecieron mayoritariamente a tres grupos terapéuticos: antiinfecciosos de uso sistémico (171; 48,7%), sistema nervioso (66; 18,8%) y sistema respiratorio (41; 11,7%).Conclusiones: La incidencia de incidentes por medicamentos en los pacientes pediátricos que acudieron a servicios de urgencias fue inferior a la referida en pacientes adultos, si bien prácticamente la mitad de los incidentes detectados causaron daños a los pacientes. Los niños preescolares (1-5 años) fueron identificados como el grupo de edad con mayor riesgo. Los incidentes registrados estuvieron causados por un número reducido de medicamentos. Un elevado porcentaje de los incidentes fueron prevenibles, lo que confirma la imperiosa necesidad de implementar medidas de prevención de incidentes en esta población.

Population pharmacokinetics of phenobarbital in Caucasian patients with epilepsy.

The present study aimed to establish a population pharmacokinetic (PopPK) model of Phenobarbital (PB) in Caucasian patients with epilepsy included in a Therapeutic Drug Monitoring program. In total, 855 PB serum concentrations (steady-state trough concentrations) were retrospectively collected during routine clinical monitoring of 395 patients over 15 years of age with epilepsy. The PopPK analysis was performed with NONMEM using a non-linear mixed-effect modelling approach. The influence of demographic, anthropometric, treatment, and comedication variables on the apparent clearance (CL/F) of PB were analysed. Goodness of fit plots and the bootstrap method were performed to evaluate the final model. External validation was carried out using an independent group of patients (107 patients, 178 blood samples). A one-compartment model with first-order absorption and elimination successfully described the data. In the final model, CL/F included body surface area (BSA) and comedication with phenytoin (PHT) and valproic acid (VPA), resulting in the following equation: CL/F[L/h]=(0.236+(0.115×(BSA-1.7)))×(0.822PHT)×(0.711VPA) The model presents acceptable estimation errors in the parameters of fixed (<12%) and random effects (<13%), and of the shrinkage values (<21%). Internal and external validations demonstrated the good predictability of the final model. A PopPK model of PB in Caucasian patients over 15 years of age was successfully established, which can be used to estimate phenobarbital CL/F. BSA and drug-drug interactions with PHT and VPA should be incorporated into dosing decisions. This PopPK, using Bayesian algorithms, could help establish an optimal dosage regimen in routine patient care.

Randomised multicentre clinical trial to evaluate voriconazole pre-emptive genotyping strategy in patients with risk of aspergillosis: vorigenipharm study protocol.

INTRODUCTION: Invasive aspergillosis is the most important cause of morbidity and mortality in patients with haematological diseases. At present, voriconazole is the first-line treatment for invasive fungal disease. The pharmacokinetic interindividual variability of voriconazole depends on genetic factors. CYP450 is involved in 70%-75% of total metabolism of voriconazole, mainly CYP3A4 and CYP2C19, with the remaining 25%-30% of metabolism conducted by monooxygenase flavins. CYP2C19 single nucleotide polymorphisms could explain 50%-55% of variability in voriconazole metabolism. MATERIALS AND METHODS: The main objective is to compare efficiency of pre-emptive voriconazole genotyping with routine practice. The primary outcome is serum voriconazole on the fifth day within the therapeutic range. The secondary outcome is the combined variables of therapeutic failure and adverse events within 90 days of first administration, associated with voriconazole. A total of 146 patients at risk of invasive aspergillosis who will potentially receive voriconazole will be recruited, and CYP2C19 will be genotyped. If the patient ultimately receives voriconazole, they will be randomised (1:1 experimental/control). In the experimental arm, patients will receive a dose according to a pharmacogenetic algorithm, including CYP2C19 genotype and clinical and demographic information. In the control arm, patients will receive a dose according to clinical practice guidelines. In addition, a Spanish National Healthcare System (NHS) point-of-view cost-effectiveness evaluation will be performed. Direct cost calculations for each arm will be performed. CONCLUSION: This trial will provide information about the viability and cost-effectiveness of the implementation of a pre-emptive voriconazole genotyping strategy in the Spanish NHS. ETHICS AND DISSEMINATION: A Spanish version of this protocol has been evaluated and approved by the La Paz University Hospital Ethics Committee and the Spanish Agency of Medicines and Medical Devices. Trial results will be submitted for publication in an open peer-reviewed medical speciality-specific publication. TRIAL REGISTRATION NUMBER: Eudra-CT: 2019-000376-41 and NCT04238884; Pre-results.

Recommendations by the Spanish Society of Hospital Pharmacy, the Spanish Society of Oncology Nursing and the Spanish Society of Medical Oncology for the safe management of antineoplastic medication in cancer patients.

OBJECTIVE: To define recommendations that permit safe management of  antineoplastic medication, minimise medication errors and improve the safety of  cancer patients undergoing treatment. METHOD: By reviewing the literature and consulting the websites of various health organisations and agencies, an expert committee from the  Spanish Society of Hospital Pharmacy and the Spanish Society of Medical  Oncology defined a set of safe practices covering all stages of providing cancer  therapy to patients. The Spanish Society of Oncology Nursing revised and  endorsed the final list. RESULTS: In total, 68 recommendations arranged in 5 sections were defined. They include issues concerning the training of health professionals, the technological resources needed, treatment planning, informing the patient and his family, the processes of prescribing, preparing, dispensing and administering cancer therapy (orally, parenterally or intrathecally),  assessing patient adherence and treatment toxicity. CONCLUSIONS: It is essential for healthcare establishments to implement specific  measures designed to prevent medication errors, in order to ensure the safety of  cancer patients treated with antineoplastic medication.

Objetivo: Definir unas recomendaciones que permitan el manejo seguro de la  medicación antineoplásica, minimizar los errores de medicación y mejorar la  seguridad de los pacientes oncológicos tratados.Método: A partir de una revisión de la bibliografía, así como de la consulta de  páginas web de varias agencias y organismos sanitarios, un comité de expertos  de la Sociedad Española de Farmacia Hospitalaria y la Sociedad Española de  Oncología Médica han definido una serie de prácticas seguras para todas las  etapas de la provisión del tratamiento antineoplásico al paciente. La Sociedad  Española de Enfermería Oncológica revisó y respaldó la lista final.Resultados: Se han definido 68 recomendaciones estructuradas en 5 secciones. Se incluyen aspectos relacionados con la formación de los profesionales  sanitarios; los recursos tecnológicos necesarios; la planificación del tratamiento;  la información al paciente y a sus familiares; los procesos de prescripción,  preparación, dispensación y administración del tratamiento antineoplásico (por  vía oral, parenteral o intratecal), así como la evaluación de la adherencia del  paciente y la toxicidad del tratamiento.Conclusiones: El establecimiento de medidas concretas destinadas a prevenir  los errores de medicación en los centros sanitarios es esencial para garantizar la  seguridad de los pacientes oncológicos tratados con medicación antineoplásica.