Key Learning Outcomes for Clinical Pharmacology and Therapeutics Education in Europe: A Modified Delphi Study.

Harmonizing clinical pharmacology and therapeutics (CPT) education in Europe is necessary to ensure that the prescribing competency of future doctors is of a uniform high standard. As there are currently no uniform requirements, our aim was to achieve consensus on key learning outcomes for undergraduate CPT education in Europe. We used a modified Delphi method consisting of three questionnaire rounds and a panel meeting. A total of 129 experts from 27 European countries were asked to rate 307 learning outcomes. In all, 92 experts (71%) completed all three questionnaire rounds, and 33 experts (26%) attended the meeting. 232 learning outcomes from the original list, 15 newly suggested and 5 rephrased outcomes were included. These 252 learning outcomes should be included in undergraduate CPT curricula to ensure that European graduates are able to prescribe safely and effectively. We provide a blueprint of a European core curriculum describing when and how the learning outcomes might be acquired

Estudio de incidentes y Eventos Adversos en la atención ambulatoria en países de América Latina

Introducción y objetivo: La seguridad del paciente es una prioridad para las organizaciones sanitarias de todo el mundo. A pesar de existir ya muchos estudios, pocos se han realizado a nivel ambulatorio en América Latina. El objetivo de este trabajo es determinar la frecuencia y evitabilidad de los eventos adversos (EA) en la asistencia ambulatoria en centros seleccionados de América Latina. Metodología: Se diseñó estudio observacional de cohorte con medición retro y prospectiva. La población a estudio fueron pacientes de edad igual o mayor de 18 años, atendidos en servicios ambulatorios de Brasil, Colombia, México y Perú. Se consideró una incidencia esperada de 1% de EA con un margen de error de 0.5%, un nivel de confianza de 95% y un porcentaje de pérdidas del 10%, el tamaño muestral considerado fue de 1866 pacientes. Se estudiaron el número de EA durante los seis meses anteriores a la consulta médica y durante los 42 días posteriores. Se analizó el tipo de EA, sus causas y determinantes, el impacto y la discapacidad provocada en el paciente, y la evitabilidad de los mismos. La fuente para la detección de EA fue el paciente a través de entrevista. Muestreo por conveniencia de los centros sanitarios. Resultados. Participaron 232 médicos y 2080 pacientes. Se notificaron 180 incidentes que afectaron a 108 pacientes, de los cuales 116 fueron EA. La prevalencia de período de EA fue del 5,6% (116/2080; IC 95% 4,6‐6,6), 108 pacientes (7,4%) tuvieron más de un EA siendo la prevalencia por paciente del 5,2% (108/2080) (IC 95% 4,2‐6,1). Casi un 75% de los EA se relacionaron con la medicación, básicamente a reacciones adversas a medicamentos, seguidos de errores en la prescripción (9%) y de fallos de comunicación (9%). El impacto en el paciente fue grave en un 8,6% de los casos siendo más frecuente entre mujeres, del grupo de edad entre 46 y 64 años y con menores recursos económicos. El grado de discapacidad asociada fue leve o moderada en 34,5% (40/116). Un 35,4% (40 EA) fueron considerados evitables. El 70% de los relacionados con la comunicación y el 60% de los EA relacionados con la prescripción fueron considerados evitables con total certeza. La evitabilidad se asoció al nivel socioeconómico bajo, bajo/medio y medio del paciente (OR 3,6 IC 95% 1,2‐10,6) y a errores de medicación (OR 0,1, IC 95% 0,0‐0,5). La incidencia acumulada fue del 2,4% (42/1757; IC 95% 1,7‐3,1) siendo casi el 60% debidos a la medicación. El 31,7% (13 EA) se consideraron evitables. Conclusiones: Se ha estimado la frecuencia de los EA en 4 países de Latinoamérica. La prevalencia de Evento Adverso ha sido del 5,6% y en un 7,4% de ellos ha ocurrido más de un EA y la incidencia de EA ha sido del 2,4% con una pérdida del 15,5 % de los pacientes incluidos en la primera fase del estudio. Al igual que en la literatura, los medicamentos, la prescripción y la comunicación son las causas más frecuentes de EA. Más de una tercera parte de los EA son evitables. Finalmente, la metodología del estudio es trasladable a otras áreas del sistema sanitario y a otros países.Introduction and Objective: Patient safety is a priority for health organizations around the world. Research on this subject is plentiful, yet little has been done on the subject in ambulatory care in Latin America. The aim of the study was to determine the frequency and prevention of Adverse Effects (AE) in ambulatory care facilities in a number of selected hospitals in Latin American. Methodology: Multinational observational cohort study with a retrospective and prospective approach. The study population were patients over 18 years old attended in ambulatory healthcare facilities from Brazil, Colombia, Mexico and Peru. A minimum sample size of 1866 patients was initially estimated for an AE incidence of 1%, a margin of error of 0.5% and a 95% confidence interval (CI). The AE ocurred six months prior to the ambulatory consultation and 42 days after it were collected. We analyzed the AE in terms of prevention, of patients´ daily activities disruption, as well as the causes and consequences of AE. Interviews with the patients were determinant in detecting AE. Convenience sampling was performed in ambulatory healthcare centers. Results: 232 doctors and 2080 patients participated in the project. A total of 180 incidents were detected, which affected 108 patients. The prevalence of AE was 5.6% (116/2080, 95% CI 4.6‐6.6), 108 patients (7.4%) had more than one AE, being the prevalence per patient of 5,2% (108/2080) (95% CI 4.2‐6.1).Almost 75% of the AE were caused by/or related to medication, basically adverse drug reactions, followed by prescription errors (9%) and communication problems (9%). The impact of these AE on patients was severe in 8.6% of total AE and more frequent in women, in the age group from 46 to 64 and in lower income patients. The level of disability caused by AE was mild or moderate in 34.5% of cases (40/116). 70% /seventy percent of the AE related to/due to communication issues and 60% of the AEs related to prescription (errors) were considered preventable with total certainty. Preventability was associated with the low, low‐middle and middle socioeconomic status of the patient (OR 3.6 95% CI 1.2 to 10.6) and with medication errors (OR 0.1, 95% CI 0.0 to 0.5). The incidence of AE was 2.4% (42/1757; 95% CI 1.7‐3.1), with almost 60% of them due to medication. The 31.7% (13 AE) were considered avoidable. Conclusions: We estimate the frequency of AE in ambulatory care in 4 countries of Latin America. The a prevalence of AE 5.6% and in 7.4% of them more than one AE has occurred and incidence of AE has been 2.4% with a loss of 15.5% of the patients included in the first phase of the study. As in the literature, medications, prescription and communication are the most frequent causes of AE. More than one‐third of AEs are preventable. Finally, the methodology of the study is transferable to other areas of the health system and to other countries

Efficacy of psychostimulant drugs for amphetamine abuse or dependence.

Amphetamine dependence constitutes a public health problem with many consequences and complications. Amphetamine abuse refers to a maladaptive and hazardous pattern of use considered to be less severe than dependence. To date, no pharmacological treatment has been approved for amphetamine abuse or dependence, and psychotherapy remains the best treatment option. Long-term amphetamine use reduces dopamine levels in the brain. Drugs increasing dopamine and mimicking the effects of amphetamines with lower abuse liability could be used as replacement therapy in amphetamine dependence. Several psychostimulants have been studied recently for this purpose. In this review, the efficacy and safety of psychostimulants for amphetamine abuse or dependence were studied. We found eleven studies enrolling 791 amphetamine-dependent participants and assessing the effects of four different psychostimulants: dexamphetamine, bupropion, methylphenidate and modafinil. Psychosocial interventions were additionally provided to all participants. The studies were conducted in the USA, Australia or Northern Europe, and study length ranged from 8 to 20 weeks. Psychostimulants did not reduce amphetamine use or amphetamine craving and also did not increase sustained abstinence in comparison with placebo. Retention in treatment was similar and low with both treatments. Psychostimulants also did not increase the risk of adverse events that were intense enough to induce dropouts. Research with larger and longer trials is needed to determine whether psychostimulants can be a useful replacement therapy for patients with amphetamine abuse or dependence. The design of future trials should consider the level of dependence at study entry, the potency and the dose of the psychostimulant administered, the length of the trial and the representativeness of included participants

Psychostimulant drugs for cocaine dependence.

Objective: To ascertain the efficacy of psychostimulants for cocaine dependence on cocaine use, sustained cocaine abstinence and retention in treatment. The influence of type of drug, comorbid disorders and clinical trial reporting quality over psychostimulants efficacy has also been studied. Cocaine dependence is a frequent disorder for which no medication has clearly proved to be efficacious. Substitution therapy involves the replacement of abused drug, which is often illegal, used several times a day, by a legal, orally administered one. A substitutive drug has similar effects to the abused one, but with a lower addictive potential therefore leading to drug abstinence and involving patients to follow medical and psychological assistance. This strategy has proved to be efficacious for heroin and nicotine dependence. In this review we investigated if psychostimulant substitution was efficacious for cocaine dependence. We found that sixteen studies that had enrolled 1,345 patients investigated the efficacy of psychostimulants against placebo for cocaine dependence. Seven drugs with psychostimulant effect or metabolized to a psychostimulant have been investigated: bupropion, dexamphetamine, methylphenidate, modafinil, mazindol, methamphetamine and selegiline. Psychotherapy was provided in all clinical trials. Study length ranged from 6 to 24 weeks. Psychostimulants did not improve cocaine use, had an unclear beneficial effect over sustained cocaine abstinence and were not associated with higher retention in treatment. Psychostimulants did not increase risk of serious adverse events. It was found that psychostimulants could be efficacious for some groups of patients, such as methadone maintained dual heroin-cocaine addicts. Therefore, psychostimulants, though have not proved yet their efficacy for cocaine dependence, deserve further investigation

Detection of early seeding of Richter transformation in chronic lymphocytic leukemia

Richter transformation (RT) is a paradigmatic evolution of chronic lymphocytic leukemia (CLL) into a very aggressive large B cell lymphoma conferring a dismal prognosis. The mechanisms driving RT remain largely unknown. We characterized the whole genome, epigenome and transcriptome, combined with single-cell DNA/RNA-sequencing analyses and functional experiments, of 19 cases of CLL developing RT. Studying 54 longitudinal samples covering up to 19 years of disease course, we uncovered minute subclones carrying genomic, immunogenetic and transcriptomic features of RT cells already at CLL diagnosis, which were dormant for up to 19 years before transformation. We also identified new driver alterations, discovered a new mutational signature (SBS-RT), recognized an oxidative phosphorylation (OXPHOS)(high)-B cell receptor (BCR)(low)-signaling transcriptional axis in RT and showed that OXPHOS inhibition reduces the proliferation of RT cells. These findings demonstrate the early seeding of subclones driving advanced stages of cancer evolution and uncover potential therapeutic targets for RT.Single-cell genomic and transcriptomic analyses of longitudinal samples of patients with Richter syndrome reveal the presence and dynamics of clones driving transformation from chronic lymphocytic leukemia years before clinical manifestatio