Development and Validation of Three Triplex Real-Time RT-PCR Assays for Typing African Horse Sickness Virus: Utility for Disease Control and Other Laboratory Applications.

The African horse sickness virus (AHSV) belongs to the Genus Orbivirus, family Sedoreoviridae, and nine serotypes of the virus have been described to date. The AHSV genome is composed of ten linear segments of double-stranded (ds) RNA, numbered in decreasing size order (Seg-1 to Seg-10). Genome segment 2 (Seg-2) encodes outer-capsid protein VP2, the most variable AHSV protein and the primary target for neutralizing antibodies. Consequently, Seg-2 determines the identity of the virus serotype. An African horse sickness (AHS) outbreak in an AHS-free status country requires identifying the serotype as soon as possible to implement a serotype-specific vaccination program. Considering that nowadays 'polyvalent live attenuated' is the only commercially available vaccination strategy to control the disease, field and vaccine strains of different serotypes could co-circulate. Additionally, in AHS-endemic countries, more than one serotype is often circulating at the same time. Therefore, a strategy to rapidly determine the virus serotype in an AHS-positive sample is strongly recommended in both epidemiological situations. The main objective of this study is to describe the development and validation of three triplex real-time RT-PCR (rRT-PCR) methods for rapid AHSV serotype detection. Samples from recent AHS outbreaks in Kenia (2015-2017), Thailand (2020), and Nigeria (2023), and from the AHS outbreak in Spain (1987-1990), were included in the study for the validation of these methods.

Intra-amniotic infection and/or inflammation is associated with fetal cardiac concentric hypertrophy and diastolic dysfunction in preterm labor and preterm prelabor rupture of membranes.

BACKGROUND: Preterm delivery is associated with cardiovascular remodeling and dysfunction in children and adults. However, it is unknown whether these effects are caused by the neonatal consequences of preterm birth or if these are already present in utero. OBJECTIVE: We evaluated fetal cardiac morphology and function in fetuses of mothers admitted for preterm labor or preterm prelabor rupture of membranes and the association of these changes with the presence of intra-amniotic infection and/or inflammation. STUDY DESIGN: In this prospective cohort study, fetal echocardiography and amniocentesis were performed at admission in singleton pregnant women with preterm labor and/or preterm prelabor rupture of membranes between 24.0 and 34.0 weeks' gestation with (intra-amniotic infection and/or inflammation group, n=41) and without intra-amniotic infection and/or inflammation (non-intra-amniotic infection and/or inflammation, n=54). Controls (n=48) were outpatient pregnant women without preterm labor or preterm prelabor rupture of membranes. Intra-amniotic infection was defined by a positive amniotic fluid culture or positive 16S ribosomal RNA gene. Intra-amniotic inflammation was defined by using the amniotic fluid interleukin-6 cutoff levels previously reported by our group being >1.43 ng/mL in preterm prelabor rupture of membranes and >13.4 ng/mL in preterm labor. Fetal cardiac morphology and function was evaluated using echocardiography, and troponin-I and N-terminal pro-brain natriuretic peptide concentrations were measured in amniotic fluid from women with preterm labor or preterm prelabor rupture of membranes and compared with 20 amniotic fluid Biobank samples obtained for reasons other than preterm labor or preterm prelabor rupture of membranes or cardiac pathology. The data were adjusted for the estimated fetal weight below the 10th percentile and for preterm prelabor rupture of membranes at admission and also for gestational age at amniocentesis when amniotic fluid biomarkers were compared. RESULTS: From 2018 to 2021, 143 fetuses were included; 95 fetuses were from mothers admitted with a diagnosis of preterm labor or preterm prelabor rupture of membranes, and among those, 41 (28.7%) were in the intra-amniotic infection and/or inflammation group and 54 (37.8%) were in the non-intra-amniotic infection and/or inflammation group. A total of 48 (33.6%) fetuses were included in the control group. Fetuses with preterm labor and/or preterm prelabor rupture of membranes had signs of subclinical cardiac concentric hypertrophy (median left wall thickness of 0.93 [interquartile range, 0.72-1.16] in the intra-amniotic infection and/or inflammation group; 0.79 [0.66-0.92] in the non-intra-amniotic infection and/or inflammation group; and 0.69 [0.56-0.83] in controls; P<.001) and diastolic dysfunction (tricuspid A duration 0.23 seconds [0.21-0.25], 0.24 [0.22-0.25], and 0.21 [0.2-0.23]; P=.007). Systolic function was similar among groups. Higher values of amniotic fluid troponin I (1413 pg/mL [927-2334], 1190 [829-1636], and 841 [671-959]; P<.001) and N-terminal pro-brain natriuretic peptide were detected (35.0%, 17%, and 0%; P=.005) in fetuses with preterm labor or preterm prelabor rupture of membranes when compared with the control group. The highest N-terminal pro-brain natriuretic peptide concentrations were found in the intra-amniotic infection and/or inflammation group. CONCLUSION: Fetuses with preterm labor or preterm prelabor rupture of membranes showed signs of cardiac remodeling and subclinical dysfunction, which were more pronounced in those exposed to intra-amniotic infection and/or inflammation. These findings support that the cardiovascular effects observed in children and adults born preterm have, at least in part, a prenatal origin.

Medication guide for dose adjustment and management of cardiotoxicity and lipid metabolic adverse events of oral antineoplastic therapy.

Objective: The management of cardiotoxicity concerning the use of oral antineoplastic agents (OAAs) is a challenge for healthcare professionals. Our objective was to create a comprehensive medication management guide with dose adjustment recommendations on OAAs concerning cardiotoxic and lipid metabolic adverse events (AEs) to assist healthcare professionals when prescribing OAAs. Materials and methods: A review of the available information on all dose adjustments necessary to safely prescribe and dispense OAAs concerning cardiotoxicity was conducted. In January 2023, we identified all OAAs authorized by the European Medicines Agency (EMA). For each drug, the latest summary of product characteristics (SPC) approved by the EMA and the tertiary data source Lexicomp® were reviewed. Cardiotoxic AEs were recorded, namely, QT interval prolongation, decrease in left ventricular ejection fraction (LVEF), imbalances in blood pressure (hypertension and hypotension), alterations in heart rate (tachycardia and bradycardia), and thrombosis. Any available dose adjustment recommendations in case of an occurrence of these adverse events were collected. Results: In all, 93 different OAAs had been approved by the EMA and were reviewed. Among them, 51.6% have recognized cardiotoxic AEs and 10.8% can cause alterations in lipid metabolism. A total of 27 (29.0%) OAAs had specific recommendations regarding QT prolongation; 88.9% were listed in the SPC and 59.3% in Lexicomp®. Eight OAAs (9.68%) have reported a decrease in LVEF, and four of these drugs, namely, encorafenib, lorlatinib, ripretinib, and sunitinib, have specific management recommendations. Almost half (49.5%) of currently approved OAAs can potentially alter blood pressure; 34 (36.6%) of them have been reported to cause hypertension and 12 (12.9%) are related to hypotension. Tachycardia and/or bradycardia are associated with 22.6% and 8.6% of the evaluated drugs, respectively. Regarding thrombosis, 30 (32.3%) of the drugs analyzed included the appearance of a thrombus as a possible AE. Conclusions: More than half of the OAAs can produce cardiotoxic effects, with the most frequent being blood pressure alteration and QT interval prolongation with a non-depreciable incidence of LV dysfunction or thrombosis. Before starting the treatment, it is necessary to stratify baseline cardiovascular risk, plan a surveillance schedule, and consider referral to cardio-oncology units.

Possible heart failure caused by osimertinib in a lung cancer patient.

INTRODUCTION: Osimertinib is a third-generation tyrosine kinase inhibitor (TKI) indicated for the treatment of epidermal growth factor receptor mutated non-small cell lung cancer (NSCLC). It has demonstrated better results concerning effectiveness than other TKIs for the same indication. However, despite a good safety profile, it could produce some cardiotoxicity that does not occur with other drugs of the same group. CASE REPORT: We report the evolution and management of a female patient diagnosed with NSCLC who developed a grade 3 cardiotoxicity due to treatment with osimertinib. This patient suffered from a left bundle branch block, dyslipidemia, and hypertension as cardiovascular risk factors. After a long period of treatment with osimertinib, she developed a severe heart failure (HF) with an important decrease in left ventricular ejection fraction (LVEF), which triggered an admission to the oncology unit for eight days. MANAGEMENT AND OUTCOMES: Treatment with osimertinib was first suspended and then resumed after stabilization of the HF. She also developed atrial fibrillation during admission and has required narrow cardiac monitoring and management since the debut of the HF. After evaluating the benefit-risk balance, osimertinib was reintroduced and the patient continues in treatment at the moment, although the baseline LVEF is not recovered. DISCUSSION: There is scarce evidence in the literature concerning HF and important LVEF decrease due to osimertinib. However, its severity and repercussion for the patient justify the thorough screening of cardiovascular risk factors before starting the therapy.

Complementary and alternative medicine in cancer patients: characteristics of use and interactions with antineoplastic agents.

PURPOSE: Our objectives were to analyze the use of complementary and alternative medicine (CAM) in cancer patients and to describe the incidence and characteristics of interactions between CAM and antineoplastic agents. METHODS: We performed an observational study in cancer outpatients at a university hospital. Variables were collected through a 22-item questionnaire. Potential interactions between CAM and antineoplastic agents were analyzed using the Lexicomp®, the About Herbs®, and the summary of product characteristics. Mechanism of action, reliability, and the potential clinical effect of interactions were analyzed. RESULTS: The study population comprised 937 patients, of whom 65% used CAM (70.6% herbal products, 25.8% dietary supplements, and 3.6% homeopathy). Female sex, younger age, and breast cancer were associated with more frequent use of CAM. The primary source of information about CAM was friends and family (43.5%). A total of 335 (57.1%) patients did not tell their doctor that they took CAM. The five most common CAM were chamomile, green tea, pennyroyal mint, linden, and rooibos. At least one interaction between CAM and antineoplastic agents was reported by 65.0% of CAM users (33.9% of all patients). Depending on the mechanism of action, 80% of CAM diminished the metabolism of the antineoplastic agents. CONCLUSION: Our results reveal a high incidence of interactions between CAM and antineoplastic agents. The most frequent CAM were herbal products. Family and friends were the primary sources of information that led patients to start taking CAM, and more than half of the patients did not tell their doctor that they were taking CAM.

Design and implementation of a mobile app for the pharmacotherapeutic follow-up of patients diagnosed with immune-mediated inflammatory diseases: eMidCare.

Background: Pharmacotherapeutic management of immune-mediated inflammatory diseases (IMID) has become more complex due to the development of new treatments, such as biological therapies. Mobile health, especially apps, can provide IMID patients with greater autonomy and facilitate communication with healthcare professionals. Our objective was to design and implement an app for remote monitoring and communication with IMID patients. Methods: A multidisciplinary group was created to design and develop an app for IMID patients in a tertiary hospital. The app functionalities were identified through a focus group with IMID patients and through an observational, descriptive study of available apps for IMID patients at App Store and Play Store platforms. Once the app was designed and developed, we offered the app to IMID patients who initiated a new biological therapy. The inclusion period was from December 2020 to August 2021. We performed an observational, longitudinal study to assess the app's impact on medication safety, communication, satisfaction, and usability. Results: We designed an app (eMidCare®) with the following modules: My Medication, My Questionnaires, Adverse Events, Useful Information, Messages, and Patient Profile. A total of 85 patients were installed with the app. The median (range) follow-up time for app use was 123 (5-270) days. In the My Medication module, 100% of patients registered their biological therapy and 25.9% also used this module to record each dose of medication administered. A total of 82 adverse events (AEs) were registered. Thirty-two percent of the patients registered at least 1 AE. The most frequent AEs were fatigue, injection site reaction, headache, and nausea. Fifty-two percent of patients used the Messages module to communicate with healthcare professionals. The most frequent messages concerned doubts about managing AEs (26.2%) and drug interactions (18.9%). The satisfaction survey yielded a median (range) score of 9.1 (7-10) out of 10. Conclusions: We developed an app, eMidCare®, which reminds patients to take their medication, enables them to record AEs, and helps them communicate with healthcare professionals. Approximately one-third of the patients registered the administration of the biological therapies and registered at least 1 AE. The most used and most satisfactory functionality was communication with health professionals.

Smartphone-Based Ecological Momentary Assessment for the Measurement of the Performance Status and Health-Related Quality of Life in Cancer Patients Under Systemic Anticancer Therapies: Development and Acceptability of a Mobile App.

Background: We have defined a project to develop a mobile app that continually records smartphone parameters which may help define the Eastern Cooperative Oncology Group performance status (ECOG-PS) and the health-related quality of life (HRQoL), without interaction with patients or professionals. This project is divided into 3 phases. Here we describe phase 1. The objective of this phase was to develop the app and assess its usability concerning patient characteristics, acceptability, and satisfaction. Methods: The app eB2-ECOG was developed and installed in the smartphone of cancer patients who will be followed for six months. Criteria inclusion were: age over 18-year-old; diagnosed with unresectable or metastatic lung cancer, gastrointestinal stromal tumor, sarcoma, or head and neck cancer; under systemic anticancer therapies; and possession of a Smartphone. The app will collect passive and active data from the patients while healthcare professionals will evaluate the ECOG-PS and HRQoL through conventional tools. Acceptability was assessed during the follow-up. Patients answered a satisfaction survey in the app between 3-6 months from their inclusion. Results: The app developed provides a system for continuously collecting, merging, and processing data related to patient's health and physical activity. It provides a transparent capture service based on all the available data of a patient. Currently, 106 patients have been recruited. A total of 36 patients were excluded, most of them (21/36) due to technological reasons. We assessed 69 patients (53 lung cancer, 8 gastrointestinal stromal tumors, 5 sarcomas, and 3 head and neck cancer). Concerning app satisfaction, 70.4% (20/27) of patients found the app intuitive and easy to use, and 51.9% (17/27) of them said that the app helped them to improve and handle their problems better. Overall, 17 out of 27 patients [62.9%] were satisfied with the app, and 14 of them [51.8%] would recommend the app to other patients. Conclusions: We observed that the app's acceptability and satisfaction were good, which is essential for the continuity of the project. In the subsequent phases, we will develop predictive models based on the collected information during this phase. We will validate the method and analyze the sensitivity of the automated results.

A New Methodology to Estimate Drug Cost Avoidance in Clinical Trials: Development and Application.

Background: Oncology clinical trials can lead to relevant financial savings in drug acquisition for healthcare providers. Considerable methodological heterogeneity is observed among previous studies estimating these savings. Methods: We developed a methodology to estimate the economic benefit obtained from the enrollment of patients into clinical trials through the analysis of drug cost avoidance. We designed a decision algorithm to determine if a clinical trial is associated with drug cost avoidance. This algorithm is based on five scenarios according to the availability or not of standard treatment, the presence or absence of a control arm (placebo or active treatment), and the provider of the medication. We considered as reference the cost of the standard treatment that the patient would have received in routine clinical practice. We standardized drug doses and treatment durations according to the literature. Costs were considered from a National Health System perspective. We applied this methodology at a single, research-active University Hospital in 2019. A cost avoidance analysis per trial and patient was carried out on cancer patients. Results: We analyzed 140 trials in which 198 patients were recruited. Drug cost avoidance was found in 120 trials (85.7%). The estimated total drug cost avoidance amounted to over €3,200,000. Melanoma and genitourinary tumors were the tumor types associated with the highest cost avoidance. The average drug cost avoidance per patient was €16,245. Conclusion: We describe a standardized method to estimate drug cost avoidance in clinical trials. We have applied it to all ongoing oncology clinical trials in our center. This methodology could be valuable for other centers to analyze the potential saving of clinical trials.

Individualized treatment of preterm premature rupture of membranes to prolong the latency period, reduce the rate of preterm birth, and improve neonatal outcomes.

BACKGROUND: Preterm premature rupture of membranes complicates approximately 3% of pregnancies. Currently, in the absence of chorioamnionitis or placental abruption, expectant management, including antenatal steroids for lung maturation and prophylactic antibiotic treatment, is recommended. The benefits of individualized management have not been adequately explored. OBJECTIVE: This study aimed to compare the impact of 2 different management strategies of preterm premature rupture of membranes in 2 tertiary obstetrical centers on latency of >7 days, latency to birth, chorioamnionitis, funisitis, and short-term adverse maternal and neonatal outcomes. STUDY DESIGN: This was a multicenter retrospective study of women with singleton pregnancies with preterm premature rupture of membranes from 23 0/7 to 33 6/7 weeks of gestation between 2014 and 2018 and undelivered within 24 hours after hospital admission managed at Sunnybrook Health Sciences Center, Toronto, Canada (standard management group), and BCNatal (Hospital Clínic of Barcelona and Hospital Sant Joan de Déu Barcelona), Barcelona, Spain (individualized management group), following local protocols. The standard management group received similar management for all patients, which included a standard antibiotic regimen and routine maternal and fetal surveillance, whereas the individualized management group received personalized management on the basis of amniocentesis at hospital admission (if possible), to rule out microbial invasion of the amniotic cavity and targeted treatment. The exclusion criteria were cervical dilatation >2 cm, active labor, contraindications to expectant management (acute chorioamnionitis, placental abruption, or abnormal fetal tracing), and major fetal anomalies. The primary outcome was latency of >7 days, and the secondary outcomes included latency to birth, chorioamnionitis, and short-term adverse maternal and neonatal outcomes. Statistical comparisons between groups were conducted with propensity score weighting. RESULTS: A total of 513 pregnancies with preterm premature rupture of membranes were included in this study: 324 patients received standard management, and 189 patients received individualized management, wherein amniocentesis was performed in 112 cases (59.3%). After propensity score weighting, patients receiving individualized management had a higher latency of >7 days (76.0% vs 41.6%; P<.001) and latency to birth (18.1±14.7 vs 9.7±9.7 days; P<.001). Although a higher rate of clinical chorioamnionitis was suspected in the individualized management group than the standard group (34.5% vs 22.0%; P<.01), there was no difference between the groups in terms of histologic chorioamnionitis (67.2% vs 73.4%; P=.16), funisitis (57.6% vs 58.1%; P=.92), or composite infectious maternal outcomes (9.1% vs 7.9%; P=.64). Prolonged latency in the individualized management group was associated with a significant reduction of preterm birth at <32 weeks of gestation (72.1% vs 90.5%; P<.001), neonatal intensive care unit admission (75.6% vs 83.0%; P=.046), and neonatal respiratory support at 28 days of life (16.1% vs 26.1%; P<.01) compared with that in the standard management group. Moreover, prolonged latency was not associated with neonatal severe morbidity at discharge (survival without severe morbidity, 80.4% vs 73.5%; P=.09). CONCLUSION: Individualized management of preterm premature rupture of membranes may prolong pregnancy and reduce preterm birth at <32 weeks of gestation, the need for neonatal support, and neonatal intensive care unit admissions, without an increase in histologic chorioamnionitis, funisitis, neonatal infection-related morbidity, and short-term adverse maternal and neonatal outcomes.

Potential negative pharmacodynamic interaction of spironolactone and abiraterone in two prostate cancer patients.

INTRODUCTION: Spironolactone when combined with abiraterone in metastatic castration-resistant prostate cancer (mCRPC) may theoretically exert androgenic properties, thereby compromising the therapeutic effectiveness of abiraterone. CASE REPORT: Two patients with a medical history of cardiovascular disease and mCRPC combined spironolactone within the course of abiraterone regimen. The abiraterone-spironolactone interaction was identified using the Lexicomp® interaction tool (classified as risk C). MANAGEMENT & OUTCOME: Spironolactone treatment was maintained as it was considered beneficial due to the cardiac condition. The prostate-specific antigen (PSA) levels started to rise when these two drugs were used together. Eventually, tumour progression was observed. DISCUSSION: There is increasing evidence that spironolactone behaves as a selective androgen receptor modulator. Strategies to overcome abiraterone-spironolactone interaction could involve the use of eplerenone, although this drug is also controversial. The best strategy should imply a multidisciplinary evaluation by cardiologists and oncologists.

Medication guide for the perioperative management of oral antineoplastic agents in cancer patients.

BACKGROUND: Oral antineoplastic agents (OAAs) are high-risk drugs that may increase the risk of bleeding, difficulty in wound healing, or produce alterations in coagulation and/or platelet aggregation. These aspects had to be highly considered throughout the entire perioperative process. Our aim was to create a comprehensive management medication guide based on reconciliation and dose adjustment recommendations for OAAs in patients undergoing a surgical intervention. RESEARCH DESIGN AND METHODS: We analyzed all OAAs approved by the EMA in November 2020. We assessed data related to dose adjustment, drug reconciliation, coagulation disturbances, or anticoagulant interactions from the FDA and EMA summary of product characteristics. RESULTS: We analyzed 67 OAAs. We identified that 51 (76.2%) OAAs can produce alteration in the platelet count, 12 (17.9%) affect the wound healing and recovery process, and 32 (47.8%) require control and monitoring in case of combination with anticoagulants. Only 13 (19.4%) OAAs, most of them antiangiogenics, have specific recommendations for temporary suspension before surgery. CONCLUSIONS: Most OAAs require perioperative monitoring. This review can serve as an easy (simple, effective) tool to help healthcare professionals involved in patient care to manage OAAs during the perioperative process.

Assessment of diarrhea as side effect of oral targeted antineoplastic agents in clinical practice.

BACKGROUND: Diarrhea is one of the most frequent class adverse events associated with targeted oral antineoplastic agents (OAAs). Our objective was to analyze the incidence, characteristics, and severity of diarrhea in cancer patients in clinical practice. METHODS: An observational, longitudinal, and prospective study of cancer outpatients treated with targeted OAAs was carried out in a tertiary hospital. Targed OAAs analyzed were anaplastic lymphoma kinase inhibitors, BCR-ABL inhibitors, cyclin-dependent kinase inhibitors, epidermal growth factor receptor inhibitors, mTOR inhibitors, poly (ADP-ribose) polymerase inhibitors, and vascular endothelial growth factor receptor inhibitors. Patients were given a data collection form to record daily the number, severity (CTCAE version 5.0), and characteristics of stools during the first 30 days of treatment with OAAs. Multivariate analysis was performed to identify risk factors associated with the incidence of diarrhea. RESULTS: We analyzed 240 patients, of whom 28.7% experienced diarrhea (25.4% grades 1-2 and 3.3% grades 3-4). Patients treated with EGFR and VEGFR inhibitors had a higher incidence of diarrhea. The multivariate analysis revealed that taking the OAA with food was associated with a lower risk of diarrhea (OR = 0.404 [0.205-0.956], p = 0.038). CONCLUSIONS: More than a third of patients in treatment with OAAs presented diarrhea (any grade), and 22.1% of stools were semi-liquid/liquid. In multivariate analysis, taking the OAA on an empty stomach was associated with a statistically significant increase in the incidence of diarrhea.

Clinical course of severe patients with COVID-19 treated with tocilizumab: report from a cohort study in Spain.

Background: We report the long-term outcomes, changes in laboratory parameters, the incidence of secondary nosocomial infections and treatment cost of a Spanish cohort of patients with severe COVID-19 that received tocilizumab (TCZ).Methods: Retrospective cohort of PCR confirmed adult patients who received TCZ from March 1 to 24, 2020 in a tertiary hospital was analyzed. Patients were followed up until 10 May 2020.Results: We included 162 patients (median age 64 years; 70.4% male). At time of TCZ administration, 48.1% of patients were on invasive mechanical ventilation (IMV). Over a median follow-up of 53 days, 46.9% of patients were discharge in good conditions and 19.8% were still hospitalized. The overall mortality was 33.3%, being higher in patients on IMV than those who did not (46.2% vs 26.7%, P < 0.001). A significant improvement in the lymphocyte count, C-reactive protein, lactate dehydrogenase, and D-dimer was observed. Overall, 43.2% patients presented nosocomial infections, causing death in 8%. Infections were more prevalent in ICU units (63.0% vs 17.1%, P < 0.001). The total cost of TCZ was €371,784.Conclusions: Among the patients who used TCZ, one third died, regardless the improvement in some inflammatory biomarkers. The incidence of secondary nosocomial infections was high.

Potential and real drug interactions in patients treated with abiraterone or enzalutamide in clinical practice.

BACKGROUND: Abiraterone and enzalutamide, androgen receptor pathway inhibitors (ARPI) for the treatment of metastatic castration-resistant prostate cancer (mCRPC), are at high risk of potential drug interactions (PDIs). We aimed to describe PDIs and their management, and triggered adverse events (AEs) in clinical practice. METHODS: We conducted a cross-sectional study in mCRPC patients who started treatment with abiraterone or enzalutamide in a university hospital between August 1st, 2016 and July 31st, 2020. Lexicomp® was used to identify and analyze PDIs, and the clinical records to assess their management and the occurrence of AEs. RESULTS: We included 173 patients: 36.8% and 93.0% treated with abiraterone and enzalutamide, respectively, had at least 1 PDI. Globally, 6.3% of PDIs had X-risk (contraindication due to high probability of AE). Treatment was modified in 9.2% of patients and 9.8% suffered AEs due to PDIs. Factors associated with a higher risk of PDIs were polypharmacy (OR= 41.0, p  0.003) and treatment with enzalutamide (OR= 128.26, p < 0.001). CONCLUSIONS: At least two-thirds of patients treated with ARPI suffered a PDI. Overall, abiraterone would have a more favorable PDI profile. Knowing these interaction profiles may be helpful to develop a more efficient therapeutic follow-up and to select the safest treatment.

Continuity of care between hospital pharmacies and community pharmacies, and costs avoided: a pilot experience in times of COVID-19 in Spain.

Introduction: In March 2020, due to the pandemic caused by COVID-19, a pilot experience of pharmaceutical continuity of care received by hospital outpatients was launched in Cantabria, a Spanish autonomous community. Thanks to this experience, the medication was dispensed by the hospital pharmacy through the community pharmacy of the patient's choice. Our objective was to estimate the costs avoided by this practice during the months of April and May 2020. Methods: The analysis of the economic impact was carried out in terms of saved costs, from the hospital and from the social perspective. Savings associated with the avoided home delivery of medication and avoided labor productivity losses were calculated, as well as the time associated with avoided trips in monetary terms. Results: A total of 2,249 hospital-dispensed drugs were delivered through the community pharmacy in the analyzed period, with an average of 57.7 daily deliveries. The experience, which involved one hospital and 262 pharmacies of Cantabria, saved patients 93,305 km in trips to the hospital, associated with an average time saving of 1,374 hours. In terms of costs, the hospital saved on shipments by courier, estimated at €30,205, since it was the community pharmacy and the distribution warehouses that delivered the drugs. From a social perspective, this initiative saved €23,309 due to the trips (€8,907) and productivity losses (€14,402) that were avoided. Conclusions: This exceptional situation may be a good opportunity to improve the coordination between hospital pharmacies and community pharmacies in Spain, not only during the pandemic but also in the post-COVID-19 era.

Error Detection and Cost Savings With an Image-Based Workflow Management System Connected to a Computerized Prescription Order Entry Program for Antineoplastic Compounding.

OBJECTIVE: The aim of the study was to analyze both the prevalence of errors with the implementation of an image-based workflow management system during the antineoplastic compounding process, and the estimated costs associated with the negative clinical outcome if the errors had not been intercepted. METHODS: Three months after the implementation of Phocus Rx system at a hospital pharmacy department, the identification, classification (type, preparation stage, and cause), and potential severity degree (from negligible to catastrophic) of the errors intercepted were determined. The probability of an error causing an adverse event if it had reached the patient (from nil [0] to high [0.6]) and its consequences was estimated by a team of clinical pharmacists and physicians. Cost-effectiveness analysis from the hospital's perspective was performed. RESULTS: Overall, 9872 antineoplastic medications were prepared using Phocus Rx. The total compounding error rate was 0.8% (n = 78, 56 [69.2%] were related to incorrect dose, 20 [28.2%] to incorrect drug preparation or conditioning technique, and 2 [2.6%] were wrong drugs). Approximately 70% of the detected errors were classified as undetectable via the previous verification practice, with 11.55% judged to be potentially severe (n = 9) and 51.3% moderate (n = 29). Likelihood of occurrence of an adverse event was medium (0.4) to high (0.6) for 37.2% of the errors. Estimated cost ratio and return on investment were €4.21 and 321%, respectively. CONCLUSIONS: The implementation of Phocus Rx prevented antineoplastic preparation errors that would have reached the patient otherwise. In addition, acquisition of this technology was estimated to be cost-effective.

Acute pancreatitis in a patient treated with imatinib and gefitinib.

INTRODUCTION: Use of oral antineoplastic agents (OAAs) has increased significantly in recent years. OAAs currently represent 30-50% of all cancer treatments. Drug interactions are the most frequent drug-related problem affecting OAAs. We describe the case of a patient who presented acute pancreatitis, possibly induced by the concomitant use of imatinib and gefitinib. CASE REPORT: A female patient received imatinib and gefitinib for the treatment of chronic myeloid leukemia and lung adenocarcinoma, respectively. Liver function and pancreatic enzyme values gradually worsened after initiation of imatinib, and the patient was diagnosed with acute pancreatitis. MANAGEMENT AND OUTCOMES: Imatinib was discontinued owing to pancreatic toxicity. Gefitinib was subsequently discontinued owing to tumor progression. The patient received supportive measures for pancreatitis, although she eventually died 3 months after the onset of symptoms. DISCUSSION: To our knowledge, this is the first case in the medical literature of acute pancreatitis possibly induced by an interaction between imatinib and gefitinib. The interaction most likely arose because imatinib is a CYP2D6 inhibitor and could therefore impair the metabolism of gefitinib (a CYP2D6 substrate) and increase its serum concentration. This interaction is extremely rare. However, due to its severity, hepatic and pancreatic function should be carefully monitored in patients treated with imatinib and/or gefitinib and other inhibitors or inducers of CYP2D6 and CYP3A4.

Automation of in-hospital pharmacy dispensing: a systematic review.

OBJECTIVES: The current systematic review (SR) was undertaken to identify and summarise the published literature reporting on the clinical and economic value of automated in-hospital pharmacy services with a primary focus on systems supporting the dispensing of medicines. METHODS: Literature searches were conducted in MEDLINE, Embase and the Cochrane Library on 17 December 2017 to identify English-language publications investigating any automated dispensing systems (ADSs) in the inpatient setting to include central pharmacy and ward-based systems. RESULTS: 4320 publications were screened by title and abstract and 45 of 175 full publications screened were included. Grey literature searching identified an additional three publications. Therefore, 48 publications relating to ADSs were eligible for inclusion. Although a relatively large evidence base was identified as part of the current SR, the eligible studies were inconsistent in terms of their design and the format of reporting of outcomes. The studies demonstrate that both pharmacy and ward-based ADSs offer benefits over traditional manual dispensing methods in terms of clinical and economic outcomes. The primary benefits following implementation of an ADS include reductions in medication errors, medication administration time and costs. Studies examining optimisation/inventory management strategies/refill programmes for these systems suggest that optimal implementation of the ADS is required to ensure that clinical success and economic benefits are maximised. CONCLUSIONS: The published evidence suggests positive impacts of ADS and should encourage hospitals to invest in automation, with a global strategy to improve the reliability and the efficiency of the medication process. However, one of the key findings of the current SR is the need for further data from adequately powered studies reporting clinically relevant outcomes which would allow for robust, evidence-based recommendations on the return on investment of the technologies. These studies would probably contribute to a larger adoption of these technologies by European hospitals.