Investigating in VigiBase over 6000 cases of pneumonia in clozapine-treated patients in the context of the literature: focus on high lethality and the association with aspiration pneumonia.

BACKGROUND: The literature associates clozapine with pneumonia/aspiration pneumonia. RESEARCH DESIGN AND METHODS: The international pharmacovigilance database (VigiBase™) uses the information component (IC) as statistical signal. VigiBase clozapine reports were analyzed for pneumonia/aspiration pneumonia from introduction to 10 May 2023. RESULTS: There were 6392 cases of all types of pneumonia (5572 cases of pneumonia, 775 of aspiration pneumonia, and 45 combined). The IC was 3.52 for aspiration pneumonia, introduced as a VigiBase label in 2003, and 1.91 for pneumonia. Patients were reclassified as 3628 with no signs of aspiration and 1533 with signs. Signs of aspiration were strongly associated with some co-medications: olanzapine, odds ratio (OR) = 23.8, 95% confidence interval (CI), 14.9-38.0; risperidone OR = 18.6, CI, 11.4-30.4; valproic acid, OR = 5.5, CI, 4.5-6.6; and benzodiazepines OR = 5.5, CI, 4.5-6.6. In 2415 cases with completed data, fatal outcomes made up 45% (signs of aspiration made no difference), but there was wide variability from 0% (females <45 years of age; duration ≤30 days) to 76% (males >64 years of age; duration >1 year). During the first week, pneumonia was associated with 1) very high titration doses, 2) very small doses in Parkinson's disease, and 3) Japan vs other countries. CONCLUSIONS: In clozapine-treated patients: 1) at least 30% of pneumonia cases may be aspiration pneumonia, 2) stopping some co-medications may decrease the risk of aspiration pneumonia, 3) average lethality in pneumonia was 45% but may be around 75% in geriatric patients with long-term treatment, and 4) safer titrations may sometimes require 5-mg tablets.

The European List of Key Medicines for Medical Education: A Modified Delphi Study.

Rational prescribing is essential for the quality of health care. However, many final-year medical students and junior doctors lack prescribing competence to perform this task. The availability of a list of medicines that a junior doctor working in Europe should be able to independently prescribe safely and effectively without supervision could support and harmonize teaching and training in clinical pharmacology and therapeutics (CPT) in Europe. Therefore, our aim was to achieve consensus on such a list of medicines that are widely accessible in Europe. For this, we used a modified Delphi study method consisting of three parts. In part one, we created an initial list based on a literature search. In part two, a group of 64 coordinators in CPT education, selected via the Network of Teachers in Pharmacotherapy of the European Association for Clinical Pharmacology and Therapeutics, evaluated the accessibility of each medicine in his or her country, and provided a diverse group of experts willing to participate in the Delphi part. In part three, 463 experts from 24 European countries were invited to participate in a 2-round Delphi study. In total, 187 experts (40%) from 24 countries completed both rounds and evaluated 416 medicines, 98 of which were included in the final list. The top three Anatomical Therapeutic Chemical code groups were (1) cardiovascular system (n = 23), (2) anti-infective (n = 21), and (3) musculoskeletal system (n = 11). This European List of Key Medicines for Medical Education could be a starting point for country-specific lists and could be used for the training and assessment of CPT.

Revealing the reporting disparity: VigiBase highlights underreporting of clozapine in other Western European countries compared to the UK.

BACKGROUND: Pharmacovigilance studies indicate clozapine history is marked by adverse drug reactions (ADRs). OBJECTIVE: In a 2021 article, the United Kingdom (UK) had >90 % of European clozapine-related fatal outcomes in VigiBase, the World Health Organization's pharmacovigilance database. Two possibly opposing hypotheses could explain this disparity: 1) fewer reported fatal outcomes in other Western European countries mainly reflect underreporting to VigiBase, and 2) the higher number of UK reports reflects higher real relative mortality. METHODS: VigiBase reports from clozapine's introduction to December 31, 2022, were studied for ADRs and the top 10 causes of fatal outcomes. The UK was compared with 11 other top reporting Western countries (Germany, Denmark, France, Finland, Ireland, Italy, Netherlands, Norway, Spain, Sweden and Switzerland). Nine countries (except Ireland and Switzerland) were compared after controlling for population and clozapine prescriptions. RESULTS: The UK accounted for 29 % of worldwide clozapine-related fatal outcomes, Germany 2 % and <1 % in each of the other countries. The nonspecific label "death" was the top cause in the world (46 %) and in the UK (33 %). "Pneumonia" was second in the world (8 %), the UK (12 %), Ireland (8 %) and Finland (14 %). Assuming that our corrections for population and clozapine use are correct, other countries underreported only 1-10 % of the UK clozapine fatal outcome number. CONCLUSIONS: Different Western European countries consistently underreport to VigiBase compared to the UK, but have different reporting/publishing styles for clozapine-related ADRs/fatal outcomes. Three Scandinavian registries suggest lives are saved as clozapine use increases, but this cannot be studied in pharmacovigilance databases.

An expert review of clozapine in Latin American countries: Use, monitoring, and pharmacovigilance.

There is growing interest in clozapine clinical use, monitoring, and research, particularly adverse drug reactions (ADRs) other than agranulocytosis. In this study we focused on clozapine pharmacovigilance. Hence, we contacted clinicians and researchers in Latin America and requested information about local psychiatric services, clozapine availability, clinical use, and ADR monitoring with the VigiBase system. Only two countries have the minimum recommended number of psychiatric beds (15 per 100,000 residents): Uruguay (N = 34.9) and Argentina (N = 17). Bolivia is the only country where clozapine is unavailable. Nine out of twenty countries (45 %) reported ADRs to VigiBase. Argentina, Brazil, Chile, Colombia, and Mexico published national guidelines for schizophrenia treatment. Chile is the sole country with clozapine clinics with drug serum monitoring. Ethnicity-related drug titration in not described in package inserts in any country. We examined in detail the 9 most frequent and important clozapine ADRs in the worldwide database (pneumonia, sudden death, cardiac arrest, agranulocytosis, myocarditis, constipation, arrhythmia, seizure, and syncope). These 9 ADRs led to 294 reports with fatal outcomes in Argentina (N = 3), Brazil (N = 3), Chile (N = 2), and Peru (N = 1). Agranulocytosis was reported from 7 countries: constipation or seizures from 8 countries. Only two countries reported pneumonia and one country reported myocarditis. The number of clozapine reports in VigiBase has no relationship to the country's population. All Latin American countries underreport clozapine associated ADRs. Latin American governments, along with clinicians, researchers, and educators, should optimize clozapine use and monitoring for the benefit of people with severe mental and some neurological disorders.

Clozapine-associated pericarditis and pancreatitis in children and adolescents: A systematic literature review and pharmacovigilance study using the VigiBase database.

BACKGROUND: The literature has paid very little attention to pericarditis, pericardial effusion and pancreatitis during clozapine treatment in children and adolescents. METHODS: Cases of clozapine-associated pericarditis and pancreatitis in children were studied using searches in: 1) PubMed (June 16, 2023), and 2) the World Health Organization's pharmacovigilance database (June 1, 2022), VigiBase. VigiBase uses a logarithmic measure of disproportionality called the information component (IC). RESULTS: The PubMed search yielded 3 clozapine-associated pericarditis cases, 1 pancreatitis case and 1 with both. VigiBase provided a significant clozapine-associated pericarditis IC = 3.6 with an IC025 = 2.9 (only 3 cases were expected while 22 were observed). VigiBase provided a significant clozapine-associated pancreatitis IC = 2.2 with an IC025 = 1.4 (only 3 cases were expected while 16 were observed). In VigiBase clozapine-associated pericarditis and pericardial effusion in youth looked similar and on a continuum with myocarditis, as myocarditis, pericarditis and pancreatitis appeared to occur mainly during clozapine titration. Combining PubMed and VigiBase we identified: 1) 29 cases of at least possible clozapine-associated pericarditis/pericardial effusion (6 probable and 23 possible) including 7 cases with and 22 without myocarditis, and 2) 17 cases of clozapine-associated pancreatitis (1 definite and 16 possible). Two of the pancreatitis cases occurred during overdoses. No fatal outcomes were found in any clozapine-associated pericarditis and pancreatitis cases. CONCLUSIONS: Despite the lack of attention in the literature to clozapine-associated pericarditis and pancreatitis, results demonstrate that they can happen in youth, particularly during titration. Pericarditis and pancreatitis appear to be forms of clozapine-associated inflammation during dose titration.

An expert review of clozapine in Eastern European countries: Use, regulations and pharmacovigilance.

OBJECTIVES: To compare the prevalence, regulations, and pharmacovigilance practices of clozapine use in Eastern European countries (except Russia). METHODS: Questionnaires and data from administrative databases (2016 and 2021), package inserts and national guidelines were collected from 21 co-authors from 21 countries. Reports of clozapine adverse drug reactions (ADRs) sent to the global pharmacovigilance database (VigiBase™) were analyzed from introduction to December 31, 2022. RESULTS: Clozapine prescription among antipsychotics in 2021 varied six-fold across countries, from 2.8 % in the Czech Republic to 15.8 % in Montenegro. The utilization of antipsychotics in both 2016 and 2021 was highest in Croatia, and lowest in Serbia in 2016, and Montenegro in 2021, which had half the defined daily dose (DDD)/1000/day compared to the Croatian data. From 2016 to 2021, the prevalence of antipsychotic use increased in almost all countries; the proportion of clozapine use mainly remained unchanged. Differences were detected in hematological monitoring requirements and clozapine approved indications. Only a few national schizophrenia guidelines mention clozapine-induced myocarditis or individual titration schemes. The VigiBase search indicated major underreporting regarding clozapine and its fatal outcomes. By comparison, the United Kingdom had less than half the population of these Eastern European countries but reported to VigiBase more clozapine ADRs by 89-fold and clozapine fatal outcomes by almost 300-fold. CONCLUSION: Clozapine is under-utilized in Eastern European countries. Introducing individualized clozapine treatment schedules may help to maximize clozapine benefits and safety. Major improvement is needed in reporting clozapine ADRs and fatal outcomes in Eastern European countries.

Adverse drug reactions and their fatal outcomes in clozapine patients in VigiBase: Comparing the top four reporting countries (US, UK, Canada and Australia).

BACKGROUND: Pharmacovigilance findings and box warnings in the clozapine package inserts have marked the history of clozapine. OBJECTIVE: This is the largest review of clozapine adverse drug reactions (ADRs) and their associated fatal outcomes. Reports to the World Health Organization's global pharmacovigilance database, VigiBase™, were analyzed, extending from clozapine's introduction to December 31, 2022. METHODS: The analysis focused on the top four reporting countries: United States (US), United Kingdom (UK), Canada and Australia (83 % of fatal outcomes worldwide). Attempts were made to control for population and clozapine prescription in each country. RESULTS: Clozapine ADRs worldwide accounted for 191,557 reports, with the highest number (53,505) in "blood and lymphatic system disorder". Of the 22,596 fatal outcomes reported in clozapine patients, 9587 were from the US, 6567 from the UK, 3623 from Canada and 1484 from Australia. The top category worldwide in fatal outcomes was nonspecifically labeled "death" with 46 % (range 22-62 %). "Pneumonia" was second with 30 % (range 17-45 %). Agranulocytosis was numerically only the 35th top clozapine ADR associated with fatal outcomes. On average, 2.3 clozapine ADRs were reported per fatal outcome. Infections were associated with 24.2 % of the UK fatal outcomes (9.4 %-11.9 % in the 3 other countries). CONCLUSIONS: The four countries appeared to report clozapine ADRs in different ways, making comparisons difficult. We estimated higher fatal outcomes in the UK and Canada after controlling for cross-sectional estimations of population and published clozapine use. This last hypothesis is limited by the lack of precise estimation of accumulated clozapine use in each country.

Escaping the Long Shadow Cast by Agranulocytosis: Reflections on Clozapine Pharmacovigilance Focused on the United Kingdom.

PURPOSE/BACKGROUND: A recent article in this journal presented a US perspective regarding the modernization of clozapine prescription and proposed an escape from the long shadow cast by agranulocytosis. METHODS: Here, an international group of collaborators discusses a point of view complementary to the US view by focusing on worldwide outcomes of clozapine usage that may be uneven in terms of frequency of clozapine adverse drug reactions. FINDINGS/RESULTS: Studies from the Scandinavian national registries (Finland and Denmark) did not find increased mortality in clozapine patients or any clear evidence of the alleged toxicity of clozapine. Data on clozapine-associated fatal outcomes were obtained from 2 recently published pharmacovigilance studies and from the UK pharmacovigilance database. A pharmacovigilance study focused on physician reports to assess worldwide lethality of drugs from 2010 to 2019 found 968 clozapine-associated fatal outcomes in the United Kingdom. Moreover, the United Kingdom accounted for 55% (968 of 1761) of worldwide and 90% (968 of 1073) of European fatal clozapine-associated outcomes. In a pharmacovigilance study from the UK database (from 2008 to 2017), clozapine was associated with 383 fatal outcomes/year including all reports from physicians and nonphysicians. From 2018 to 2021, UK clozapine-associated fatal outcomes increased to 440/year. IMPLICATIONS/CONCLUSIONS: The interpretation of fatal outcomes in each country using pharmacovigilance databases is limited and only allows gross comparisons; even with those limitations, the UK data seem concerning. Pneumonia and myocarditis may be more important than agranulocytosis in explaining the uneven distribution of fatal outcomes in clozapine patients across countries.

Respiratory aspiration during treatment with clozapine and other antipsychotics: a literature search and a pharmacovigilance study in vigibase.

INTRODUCTION: Antipsychotics (APs), during treatment or overdose, may be associated with respiratory aspiration. AREAS COVERED: A PubMed search on 30 September 2022, provided 3 cases of respiratory aspiration during clozapine therapy and 1 case during an AP overdose. VigiBase records of respiratory aspiration associated with APs from inception until 5 September 2021, were reviewed. VigiBase, the World Health Organization's global pharmacovigilance database, uses a statistical signal for associations called the information component (IC). EXPERT OPINION: The ICs (and IC025) were 2.1 (and 2.0) for APs, 3.2 (and 3.0) for clozapine, 2.6 (and 2.4) for quetiapine, and 2.5 (and 2.2) for olanzapine. Cases of respiratory aspiration associated with APs included: 137 overdose/suicide cases (64 fatal) and 609 cases during treatment (385 fatal) including 333 taking clozapine (238 fatal). In logistic regression models of fatal outcomes, the odds ratios, OR, and (95% confidence intervals, CI) of significant independent variables were: a) 2.3-2.6 for clozapine in 3 samples of AP treatment of varying size, b) 1.9 (CI 1.0 to 3.5) for geriatric age in 284 patients on clozapine treatment, and c) 1.8 (CI 1.1-3.2) for antidepressant co-medication in 276 patients on non-clozapine APs. Multiple AP pharmacological mechanisms may explain respiratory aspiration.

Analysis of deprescription strategies of proton pump inhibitors in primary care: a narrative review.

BACKGROUND: Since the introduction of omeprazole in 1989, proton pump inhibitors (PPIs) have become the mainstream of treatment for acid-related pathologies, but nowadays, it is estimated that between 20% and 80% of people worldwide who are using PPIs are doing so without an approved indication. Overusing PPIs is known to involve a tremendous cost in financial terms, and many western countries have reported high spending on these medicines. OBJECTIVE: We conducted a narrative review to evaluate PPI deprescription strategies carried out entirely or in collaboration with primary care and to identify factors that could influence the success of these strategies. METHOD: This review was conducted in November 2022, following PRISMA guidelines. Four databases were searched: PubMed, Web of Science, Scopus and CINAHL Complete, using the MeSH terms 'proton pump inhibitors' AND 'deprescriptions'. RESULTS: The search with the established criteria found eight studies. The different success rates obtained by the various studies analysed in this review may be due to the different methodologies used when establishing the protocols, sample selection and monitoring of the results. CONCLUSION: We can conclude that the two factors related to the most successful strategies were a) the clarity and simplicity of the de-escalation protocols, in which patients were instructed on the measures to follow in the event of the reappearance of symptoms, and b) the training of the physicians responsible for deprescribing. Long-term conclusions cannot be drawn about the effectiveness of these protocols, given that the studies are limited in time. Other barriers to generalizing the results are the small sample size and the absence of control groups.

A Clinical Pharmacology and Therapeutics Teacher's Guide to Race-Based Medicine, Inclusivity, and Diversity.

The relationship between race and biology is complex. In contemporary medical science, race is a social construct that is measured via self-identification of study participants. But even though race has no biological essence, it is often used as variable in medical guidelines (e.g., treatment recommendations specific for Black people with hypertension). Such recommendations are based on clinical trials in which there was a significant correlation between self-identified race and actual, but often unmeasured, health-related factors such as (pharmaco)genetics, diet, sun exposure, etc. Many teachers are insufficiently aware of this complexity. In their classes, they (unintentionally) portray self-reported race as having a biological essence. This may cause students to see people of shared race as biologically or genetically homogeneous, and believe that race-based recommendations are true for all individuals (rather than reflecting the average of a heterogeneous group). This medicalizes race and reinforces already existing healthcare disparities. Moreover, students may fail to learn that the relation between race and health is easily biased by factors such as socioeconomic status, racism, ancestry, and environment and that this limits the generalizability of race-based recommendations. We observed that the clinical case vignettes that we use in our teaching contain many stereotypes and biases, and do not generally reflect the diversity of actual patients. This guide, written by clinical pharmacology and therapeutics teachers, aims to help our colleagues and teachers in other health professions to reflect on and improve our teaching on race-based medical guidelines and to make our clinical case vignettes more inclusive and diverse.

Clozapine-induced myocarditis in children and adolescents: a pharmacovigilance study using VigiBase and a systematic literature review.

INTRODUCTION: Clozapine-induced myocarditis in children (age ≤18 yo) was studied from a PubMed search (18 July 2022) (9 cases) and from the World Health Organization's pharmacovigilance database, called Vigibase, of adverse drug reaction (ADR) reports (72 non-duplicated cases). VigiBase uses a logarithmic measure of disproportionality called the information component (IC). A logistic regression model of presence/absence (40/32) of seriousness in VigiBase was developed. AREAS COVERED: VigiBase provided a significant myocarditis IC = 4.2 with an IC025 = 3.8; only 4 clozapine-induced myocarditis cases were expected, while 72 were observed. The PubMed search identified 9 cases, while VigiBase identified 72 cases (of which 67 did not overlap with published cases). These 76 combined cases included 35 doubtful (most with missing information on the day of diagnosis), 19 possible and 22 probable, according to the ADR scale. After adjusting for confounders, quetiapine increased the risk of seriousness with an odds ratio (OR) of 17.6 (95% confidence interval CI, 1.56 to 198.6), while Australian origin decreased it with an OR = 0.13 (CI, 0.04 to 0.47). EXPERT OPINION: These 41 cases of at least possible clozapine-induced myocarditis indicated that this ADR can definitively occur in children, particularly in the first 30 days of up-titration. Children's and adult cases appeared similar.

Clozapine-associated myocarditis in the World Health Organization's pharmacovigilance database: Focus on reports from various countries.

INTRODUCTION: The incidence of clozapine-associated myocarditis varies by country. These variations were explored in VigiBase, the World Health Organization's global database which has >25 million spontaneously reported adverse drug reaction (ADR) reports from 145 national drug agencies. METHODS: On January 15, 2021, a search of VigiBase since inception focused on myocarditis in clozapine patients. The 3572 individual reports were studied using the standard VigiBase logarithmic measure of disproportionality called information component (IC). The IC measures the disproportionality between the expected and the reported rates. After duplicates were eliminated there were 3274 different patients with myocarditis studied in logistic regression models. RESULTS: The first case was published in 1980 but since 1993 the VigiBase clozapine-myocarditis IC has been significant; moreover, currently it is very strong (IC=6.0, IC005-IC995=5.9-6.1) and statistically significantly different from other antipsychotics. Of the 3274 different patients with myocarditis, 43.4% were non-serious cases, 51.8% were serious but non-fatal, and 4.8% were fatal. More than half (1621/3274) of the reports came from Australia, of which 69.2% were non-serious, 27.7% serious but non-fatal, and 3.1% fatal. Asian countries contributed only 41 cases. CONCLUSIONS: In pharmacovigilance studies, confounding factors may explain statistical associations, but the strength and robustness of these results are compatible with the hypothesis that myocarditis is definitively associated with early clozapine treatment (84% [1309/1560] and 5% [82/1560] in the first and second months). Myocarditis reports from Australia are over-represented to a major degree. Asian countries may be underreporting myocarditis to their drug agencies.

Neurodevelopmental Outcomes among Brazilian Children with Cyanotic Congenital Heart Disease and Its Associated Factors.

Objectives: The aim of this study was to evaluate neurodevelopmental outcomes (motor development, nonverbal intelligence, and attention) in children with cyanotic congenital heart disease (CHD) compared with healthy children from a public hospital in southern Brazil. Materials and Methods: This was a cross-sectional study with pediatric patients of both sexes: 37 children with cyanotic CHD and a control group with 38 healthy children. Parents/guardians undertook a questionnaire and the SNAP IV scale (to evaluate attention) was applied. Two instruments were applied to each child: the R-2 Non-Verbal Intelligence test and the motor development scale. To assess the factors associated with insufficient performance in the three fields of neurodevelopment, a Poisson regression analysis was performed with a robust estimate. Results: There were no significant differences between children with cyanotic CHD and the control group for any of the neurodevelopmental outcomes studied. Low socioeconomic class was a factor associated with worse performance on the intelligence test and inattention. Furthermore, age was a factor for performance on the intelligence test, while a greater number of siblings was a factor associated with worse performance on the attention test. Conclusions: Public policies regarding child health must involve prioritizing the improvement of families' social conditions.

Clozapine-associated myocarditis in the World Health Organization's pharmacovigilance database: Focus on reports from various countries / Miocarditis asociada a la clozapina en la base de datos de farmacovigilancia de la Organización Mundial de la Salud: atención a los reportes de los diferentes países

Introduction: The incidence of clozapine-associated myocarditis varies by country. These variations were explored in VigiBase, the World Health Organization's global database which has >25 million spontaneously reported adverse drug reaction (ADR) reports from 145 national drug agencies. Methods: On January 15, 2021, a search of VigiBase since inception focused on myocarditis in clozapine patients. The 3572 individual reports were studied using the standard VigiBase logarithmic measure of disproportionality called information component (IC). The IC measures the disproportionality between the expected and the reported rates. After duplicates were eliminated there were 3274 different patients with myocarditis studied in logistic regression models. Results: The first case was published in 1980 but since 1993 the VigiBase clozapine-myocarditis IC has been significant; moreover, currently it is very strong (IC=6.0, IC005–IC995=5.9–6.1) and statistically significantly different from other antipsychotics. Of the 3274 different patients with myocarditis, 43.4% were non-serious cases, 51.8% were serious but non-fatal, and 4.8% were fatal. More than half (1621/3274) of the reports came from Australia, of which 69.2% were non-serious, 27.7% serious but non-fatal, and 3.1% fatal. Asian countries contributed only 41 cases. Conclusions: In pharmacovigilance studies, confounding factors may explain statistical associations, but the strength and robustness of these results are compatible with the hypothesis that myocarditis is definitively associated with early clozapine treatment (84% [1309/1560] and 5% [82/1560] in the first and second months). Myocarditis reports from Australia are over-represented to a major degree. Asian countries may be underreporting myocarditis to their drug agencies. (AU)

Introducción: La incidencia de la miocarditis asociada a clozapina varía en cada país, y esta variación se exploró en VigiBase™, la base de datos de la Organización Mundial de la Salud con más de 25 millones de reportes de reacciones adversas a medicamentos de 145 agencias nacionales de medicamentos. Métodos: El 15 de enero del 2021, se llevó a cabo una búsqueda en VigiBase™ de las miocarditis y clozapina. El componente de información (CI) que es una medida logarítmica de desproporción se usó para estudiar los 3.752 reportes. Con modelos de regresión logística se estudió 3.274 pacientes diferentes después de eliminar los duplicados. Resultados: El primer caso fue publicado en 1980, pero desde 1993 el CI ha sido significativo; ahora es muy alto (CI=6,0; CI005-CI995=5,9-6,1), y estadísticamente significativo de otros antipsicóticos. En los 3.274 pacientes: el 43,4% de los casos fueron no graves, el 51,4% fueron casos graves, pero no letales y el 4,8% fueron casos letales. Australia contribuyó a más de la mitad de los casos (1.621/3.274): con un 69,2% de casos no graves, un 27,7% de casos graves, pero no letales y un 3,1% de casos letales. Cuarenta y un casos fueron de países de Asia. Conclusiones: Los factores de confusión pueden explicar asociaciones estadísticas pero el tamaño y la consistencia de estos resultados son compatibles con que la miocarditis está definitivamente asociada con el tratamiento inicial de la clozapina (el 84% [1.309/1.560] fueron durante el primer mes y otro 5% [82/1.560] durante el segundo). Australia está excesivamente representada, mientras que los países de Asia parecen reportar pocos casos a sus agencias de medicamentos. (AU)

Teaching resources for the European Open Platform for Prescribing Education (EurOP2E)-a nominal group technique study.

The European Open Platform for Prescribing Education (EurOP2E) seeks to improve and harmonize European clinical pharmacology and therapeutics (CPT) education by facilitating international collaboration and sharing problem-based, online, open educational resources. The COVID-19 pandemic forced teachers to switch to virtual modalities, highlighting the need for high-quality online teaching materials. The goal of this study was to establish the online problem-based teaching resources needed to sustain prescribing education during the pandemic and thereafter. A nominal group technique study was conducted with prescribing teachers from 15 European countries. Results were analyzed through thematic analysis. In four meetings, 20 teachers from 15 countries proposed and ranked 35 teaching materials. According to the participants, the most necessary problem-based-online teaching materials related to three overarching themes. Related to learning outcomes for CPT, participants proposed creating prescription scenarios, including materials focusing on background knowledge and resources on personalized medicine and topical/ethical issues such as the prescription's impact on planetary health. Second, related to teaching, they proposed online case discussions, gamification and decision support systems. Finally, in relation to faculty development, they recommend teacher courses, a repository of reusable exam questions and harmonized formularies. Future work will aim to collaboratively produce such materials.

Respiratory aspiration during treatment with benzodiazepines, antiepileptic and antidepressant drugs in the pharmacovigilance database from VigiBase.

INTRODUCTION: Three psychotropic drug classes, benzodiazepines, antiepileptic drugs (AEDs) and antidepressants (ADs), whether used in treatment or overdose, may be associated with respiratory aspiration. Polypharmacy was defined by counting suspected drugs from these classes or two others, antipsychotics and opioids. The confounding effects of polypharmacy were considered in this study. AREAS COVERED: VigiBase records of respiratory aspiration associated with benzodiazepines, AEDs, and/or ADs from inception until 5 September 2021, were reviewed. VigiBase, the World Health Organization's global pharmacovigilance database, uses a statistical signal for associations called the information component (IC). EXPERT OPINION: The ICs (and IC025) were benzodiazepines 2.8 (and 2.6), AEDs 1.6 (and 1.5), and ADs 1.4 (and 1.3). The cases of respiratory aspiration associated with at least one drug from these 3 classes included: 1) 553 cases absent any known overdose (2.8 ± 1.7 drugs) and 2) 347 overdose cases (2.9 ± 1.8 drugs). Little support for the association of respiratory aspiration and benzodiazepine, AED or AD monotherapy in therapeutic dosages was found. Studies of the association between benzodiazepine monotherapy and respiration aspiration are needed in geriatric patients. ADs added to other medications increased lethality in all cases of respiratory aspiration including those associated with overdose, polypharmacy and/or major medical problems.

Ethical Dilemmas with Regard to Elderly Patients with Hip Fracture: The Problem of Nonagenarians and Centenarians.

Hip fracture is the most feared complication of osteoporosis, producing up to 30% mortality at the first year. With the aging of society, it is increasingly common to deal with ethical dilemmas that involve decision making in the elderly patient with a hip fracture. The objectives of the present work are to describe the main bioethical dilemmas in this group of patients and their relationship with surgical delay. We conducted a retrospective descriptive study that studied an elderly population admitted to a University Hospital with a diagnosis of hip fracture. In total, 415 patients were analyzed. The majority received surgical treatment, a correct application of the principles of justice, non-maleficence and beneficence is verified, but a possible violation of the principle of autonomy is confirmed. Based on the results of this study, the elderly population may somehow lose their principle of autonomy when they enter a hospital due to a hip fracture. On the other hand, the so-called ageism due to ignorance can influence the surgical delay and therefore the mortality of these patients.