Pharmacological Neuroenhancement: Current Aspects of Categorization, Epidemiology, Pharmacology, Drug Development, Ethics, and Future Perspectives.

Recent pharmacoepidemiologic studies suggest that pharmacological neuroenhancement (pNE) and mood enhancement are globally expanding phenomena with distinctly different regional characteristics. Sociocultural and regulatory aspects, as well as health policies, play a central role in addition to medical care and prescription practices. The users mainly display self-involved motivations related to cognitive enhancement, emotional stability, and adaptivity. Natural stimulants, as well as drugs, represent substance abuse groups. The latter comprise purines, methylxanthines, phenylethylamines, modafinil, nootropics, antidepressants but also benzodiazepines, ß-adrenoceptor antagonists, and cannabis. Predominant pharmacodynamic target structures of these substances are the noradrenergic/dopaminergic and cholinergic receptor/transporter systems. Further targets comprise adenosine, serotonin, and glutamate receptors. Meta-analyses of randomized-controlled studies in healthy individuals show no or very limited verifiability of positive effects of pNE on attention, vigilance, learning, and memory. Only some members of the substance abuse groups, i.e., phenylethylamines and modafinil, display positive effects on attention and vigilance that are comparable to caffeinated drinks. However, the development of new antidementia drugs will increase the availability and the potential abuse of pNE. Social education, restrictive regulatory measures, and consistent medical prescription practices are essential to restrict the phenomenon of neuroenhancement with its social, medical, and ethical implications. This review provides a comprehensive overview of the highly dynamic field of pharmacological neuroenhancement and elaborates the dramatic challenges for the medical, sociocultural, and ethical fundaments of society.

Trends in Discharge Prescription of Digoxin After Norwood Operation: An Analysis of Data from the Pediatric Health Information System (PHIS) Database.

Quality improvement efforts have focused on reducing interstage mortality for infants with hypoplastic left heart syndrome (HLHS). In 1/2016, two publications reported that use of digoxin was associated with reduced interstage mortality. The degree to which these findings have affected real world practice has not been evaluated. The discharge medications of neonates with HLHS undergoing Norwood operation between 1/2007 and 12/2018 at Pediatric Health Information Systems Database hospitals were studied. Mixed effects models were calculated to evaluate the hypothesis that the likelihood of digoxin prescription increased after 1/2016, adjusting for measurable confounders with furosemide and aspirin prescription measured as falsification tests. Interhospital practice variation was measured using the median odds ratio. Over the study period, 6091 subjects from 45 hospitals were included. After adjusting for measurable covariates, discharge after 1/2016 was associated with increased odds of receiving digoxin (OR 3.9, p < 0.001). No association was seen between date of discharge and furosemide (p = 0.26) or aspirin (p = 0.12). Prior to 1/2016, the likelihood of receiving digoxin was decreasing (OR 0.9 per year, p < 0.001), while after 1/2016 the rate has increased (OR 1.4 per year, p < 0.001). However, there remains significant interhospital variation in the likelihood of receiving digoxin even after adjusting for known confounders (median odds ratio = 3.5, p < 0.0001). Following publication of studies describing an association between digoxin and improved interstage survival, the likelihood of receiving digoxin at discharge increased without similar changes for furosemide or aspirin. Despite concerted efforts to standardize interstage care, interhospital variation in pharmacotherapy in this vulnerable population persists.

Keeping the Pharmacology in Pharmacoepidemiology.

The treatment of many medical conditions requires the use of multiple drugs. A study published recently in this journal nicely illustrates the need to consider the pharmacology of potentially interacting drugs when conducting pharmacoepidemiologic studies of patient safety outcomes associated with such interactions. By examining multiple streams of data, we can piece together the risks and the mechanisms of action underlying those risks, and provide useful information for clinicians and patients to use multiple pharmacotherapies safely.

Pharmacoepidemiology.

At the time of their marketing authorization, the effects of drugs and especially their efficacy have been mostly studied in randomized controlled clinical trials (RCT), comparing them to placebo or to existing drugs. However, RCT are by nature limited in their extent, and the often stringent inclusion and exclusion criteria destined to provide for homogeneous study populations reduce the generalizability of RCT results.The post-authorization evaluation of drugs (pharmacoepidemiology or real-world evidence (RWE)) covers the description of drug utilization and population risks or benefits of these drugs after they have been marketed and provided to their target populations. Though field studies have existed for a long time, modern pharmacoepidemiology has been made possible essentially by the emergence of large population databases compiled from claims data or electronic health records. The methods can be exposure or disease-based cohorts or event-driven case-based studies, tailored to the specific questions to be answered. They rely on scrupulous analysis and execution of impeccable methodology, to ensure the most reliable results possible.Pharmacoepidemiology requires knowledge of the pharmacology of drugs, of the clinical aspects of diseases and disease management, and of the epidemiological methods that can apply.

Pharmacy students' intentions to utilize pharmacoeconomics, pharmacoepidemiology, and health outcomes in future jobs.

INTRODUCTION: The objectives of this study were to explore factors associated with pharmacy students' intentions to utilize health outcomes by: (1) understanding opinions on health outcomes, (2) understanding the likelihood of using health outcomes in different settings, and (3) predicting pharmacy students' intentions to utilize health outcomes in future jobs. METHODS: This study surveyed second-year pharmacy students over two years. The survey contained four components: the theory of planned behavior, opinions on health outcomes, the likelihood of using health outcomes in different settings, and demographics. To predict pharmacy students' intentions to utilize health outcomes in future jobs, a multiple linear regression model was used with behavioral intention as the dependent variable. RESULTS: Of the 376 second-year pharmacy students surveyed, 229 responded (60.90%). Pharmacy students had a positive attitude (mean: 0.77, SD: 0.16), high level of subjective norm (mean: 0.75, SD: 0.18), high level of perceived behavioral control (mean: 0.74, SD: 0.15), and high level of behavioral intention (mean: 0.74, SD: 0.21). They thought health outcomes were important for their future jobs (mean: 0.76, SD: 0.22), and equally important as other courses in the doctor of pharmacy curriculum (mean: 0.49, SD: 0.23). Significant predictors of utilizing health outcomes in future jobs were attitude (0.21; 95% CI: 0.03, 0.40), subjective norm (0.38; 95% CI: 0.23, 0.54), and perceived behavioral control (0.45, 95% CI: 0.27, 0.63). CONCLUSIONS: The second-year pharmacy students in the program studied had positive opinions and expressed high likelihood of applying their health outcomes knowledge and skill after graduation.

Pharmacovigilance - The next chapter.

The discovery and quantification of adverse drug reactions has long relied on the careful analysis of spontaneously reported cases. Causality assessment (imputation) was a fundamental feature of individual case report analysis. This was complemented by analysis of aggregated cases, and of disproportionality analyses in spontaneous reports databases. In the absence of more specific information sources, these have resulted in the discovery of many new adverse reactions, altering drug information. It has led to the withdrawal from the market of many drugs, but its use for risk quantification remains fraught with uncertainty. The recent access to population-wide claims or electronic health records databases have confirmed for spontaneous reporting a predominant role in hypothesis generation for serious adverse drug reactions, notably those that result in hospital admission or death. In these cases, the events are identifiable at the population level, and can be quantified precisely using the tools of modern pharmacoepidemiology, to generate specific benefit-risk analyses. Spontaneous reporting remains irreplaceable in signal and alert generation in drug safety, despite its inherent limitations. For signal strengthening and assessment, more systematic and quantitative methods should be sought, such as claims databases for reactions resulting in hospital admissions.

Consumo de opioides en la Comunidad de Madrid (España) entre 2004 y 2014 / Opioid consumption in the Community of Madrid (Spain) between 2004 and 2014

Antecedentes y objetivo: El consumo de opioides es un indicador adecuado de cómo se trata el dolor. En España apenas existen estudios de la evolución del consumo y de su utilización pormenorizada en los distintos ámbitos. Materiales y métodos: Estudio analítico, observacional, retrospectivo de las prescripciones realizadas en la Comunidad de Madrid (CM) en toda la atención primaria (AP) y la atención especializada (AE) entre 2004 y 2014 y de tres grandes hospitales, para determinar la influencia de los distintos servicios en su prescripción. Resultados: El consumo de opioides en la CM entre 2004 y 2014 aumentó más de tres veces (DHD 2004: 2,67; 2014: 8,10). El tramadol fue el opioide globalmente más prescrito (DHD 2014: 4,12). Entre los de tercer escalón, el más utilizado fue el fentanilo (DHD 2014: 1,23). En AP los opioides más prescritos de tercer escalón fueron el fentanilo (DHD 2014: 0,92), seguido de la buprenorfina (DHD 2014: 0,31), la oxicodona (DHD 2014: 0,20) y el tapentadol (DHD 2014: 0,14). En AE los opioides más prescritos fueron el fentanilo (DHD 2014: 0,05), la oxicodona (DHD 2014: 0,03) y el tapentadol (DHD 2014: 0,02). En ambos casos la morfina representaba un porcentaje muy reducido (DHD 2014: AP 0,12 y AE 0,02). Por último, el opioide más utilizado en los hospitales fue la morfina (DHD 2014: 0,38), seguido del fentanilo (DHD 2014: 0,27) y la oxicodona (DHD 2014: 0,04). Los equipos de cuidados paliativos, tanto domiciliarios como hospitalarios, mostraron un consumo mayoritario de morfina (40-50% del total) y de metadona (35% del total). Conclusiones: El consumo global de opioides en la CM se triplicó entre 2004 y 2014. El tramadol y el fentanilo fueron los más prescritos del segundo y tercer escalón analgésico, respectivamente. La morfina está teniendo un papel residual en la prescripción de opioides

Background and objectives: Opioid consumption is an appropriate indicator of pain treatment. In Spain, there are scarcely any studies on the evolution of the consumption of opioids and their detailed use in the various settings. Material and methods: We conducted an analytical, observational, retrospective study of prescriptions performed in the Community of Madrid in all primary care and specialized care centres and the three major hospitals between 2004 and 2014 to determine the influence of the various departments on the prescription of opioids. Results: Opioid consumption in Madrid between 2004 and 2014 increased more than 3-fold (2.67 vs. 8.10 defined daily doses/1000 inhabitants/day [DIDs] for 2004 and 2014, respectively).Tramadol was the most widely prescribed opioid (4.12 DIDs in 2014).Among the stepIII opioids, the most widely employed was fentanyl (1.23 DIDs in 2014). In primary care, the most prescribed stepIII opioids were fentanyl (0.92 DIDs in 2014), buprenorphine (0.31 DIDs in 2014), oxycodone (0.20 DIDs in 2014) and tapentadol (0.14 DIDs in 2014). In specialized care, the most prescribed opioids were fentanyl (0.05 DIDs in 2014), oxycodone (0.03 DIDs in 2014) and tapentadol (0.02 DIDs in 2014). In both cases, morphine represented a tiny percentage (0.12 primary care and 0.02 specialized care DIDs in 2014). Lastly, the most widely used opioid in the hospitals was morphine (0.38 DIDs in 2014), fentanyl (0.27 DIDs in 2014) and oxycodone (0.04 DIDs in 2014). For the palliative care teams (both home and hospital), the most consumed opioids were morphine (40-50% of the total) and methadone (35% of the total). Conclusions: The overall consumption of opioids in Madrid tripled between 2004 and 2014. Tramadol and fentanyl were the most prescribed of the stepII andIII analgesics, respectively. The role of morphine is diminishing in the prescription of opioids

Hacia un uso juicioso de los opioides en España / Towards the judicious use of opioids in Spain

No disponible

Análisis de los problemas relacionados con los medicamentos en un hospital de tercer nivel de Barcelona / Analysis of drug-related problems in a tertiary university hospital in Barcelona (Spain)

Objetivo: Describir los problemas relacionados con la medicación detectados en pacientes ingresados y analizar el grado de aceptación de las recomendaciones propuestas. Método: Estudio observacional retrospectivo que incluyó los problemas relacionados con la medicación detectados en pacientes hospitalizados durante 2014-2015. Se realizó un análisis descriptivo y mediante regresión logística se analizó la asociación entre el grado de aceptación de la recomendación y la variable de interés. Resultados: Se detectaron 4587 problemas relacionados con la medicación en 44.870 pacientes ingresados. Los más frecuentes fueron errores de prescripción relacionados con el uso incorrecto de la orden médica informatizada (18,1%), seguidos por las interacciones (13,3%) y la necesidad de ajuste de dosis por alteración de la función renal o hepática (11,5%). El grado de aceptación de las recomendaciones realizadas que fueron valorables fue del 81,0%. El servicio médico frente al quirúrgico, determinadas intervenciones como la introducción o la suspensión de un fármaco, y la corrección de un error de prescripción, así como la comunicación verbal de la intervención al médico prescriptor, fueron las variables asociadas a un mayor grado de aceptación. Conclusiones: Los resultados de este estudio han permitido identificar áreas susceptibles de optimización mediante la introducción de estrategias de mejora, como formación sobre el modo de utilizar la orden médica informatizada, fármacos cuyo ajuste es necesario en insuficiencia renal e interacciones relevantes

Objective: To describe drug-related problems identified in hospitalized patients and to assess physicians’ acceptance rate of pharmacists’ recommendations. Methods: Retrospective observational study that included all drug-related problems detected in hospitalized patients during 2014-2015. Statistical analysis included a descriptive analysis of the data and a multivariate logistic regression to evaluate the association between pharmacists’ recommendation acceptance rate and the variable of interest. Results: During the study period 4587 drug-related problems were identified in 44,870 hospitalized patients. Main drug-related problems were prescription errors due to incorrect use of the computerized physician order entry (18.1%), inappropriate drug-drug combination (13.3%) and dose adjustment by renal and/or hepatic function (11.5%). Acceptance rate of pharmacist therapy advice in evaluable cases was 81.0%. Medical versus surgical admitting department, specific types of intervention (addition of a new drug, drug discontinuation and correction of a prescription error) and oral communication of the recommendation were associated with a higher acceptance rate. Conclusions: The results of this study allow areas to be identified on which to implement optimization strategies. These include training courses for physicians on the computerized physician order entry, on drugs that need dose adjustment with renal impairment, and on relevant drug interactions

Time trends in oral bisphosphonate initiation in Ontario, Canada over 20 years reflect drug policy and healthcare delivery changes.

Characteristics of patients starting oral bisphosphonate therapy changed over time, reflecting trends in osteoporosis management (e.g., new drugs to market), and general healthcare delivery (e.g., benzodiazepine use declined, statin use increased). When designing studies that examine osteoporosis drug effects, potential time-related biases must be considered. INTRODUCTION: To describe the type of oral bisphosphonate initiated and characteristics of patients starting oral bisphosphonate therapy over time. METHODS: We identified community-dwelling older adults (ages ≥ 66 years) initiating oral bisphosphonate therapy from April 1996 to March 2016 (1996 to 2015 fiscal years) using healthcare administrative data in Ontario. Patients with conditions other than osteoporosis that may impact bisphosphonate prescribing were excluded. The bisphosphonate initiated and patient characteristics were summarized by fiscal year and stratified by sex. RESULTS: We identified 560,817 eligible patients (81% women). Most patients initiated cyclical etidronate from 1996 until 2005, and then weekly regimens became dominant. In 2008, risedronate became the main oral bisphosphonate (46% risedronate, 43% alendronate, 11% etidronate); with its use increasing after availability of monthly and delayed-release risedronate formulations. In 2015, 71% of patients started risedronate, 28% started alendronate, and less than 2% started etidronate. Characteristics of patients changed over time, reflecting changes in osteoporosis management and general healthcare delivery. Over time, a larger proportion of men (9% to 28%) and patients with diabetes (women 10% to 17%, men 14% to 22%) initiated therapy; benzodiazepine (women 22% to 13%, men 20% to 10%) and estrogen-based hormone replacement therapy (12% to 15% of women 1996-2002 to 3% since 2008) decreased, while statin use increased (women 15% to 39%, men 14% to 52%). CONCLUSIONS: The characteristics of patients starting oral bisphosphonate therapy have changed over time. Consideration must be given to these time trends when designing studies that examine osteoporosis drug effects.

The Pharmacoepidemiology of Psychotropic Medication Use in Canadian Children from 2012 to 2016.

Objective: The goal of this study was to characterize the frequency and trends of psychotropic drug prescribing in Canadian children from 2010 to 2016 and to compare these results with a previous study conducted between 2005 and 2009. Methods: Using a national physician panel survey database from IQVIA Canada, aggregated frequencies of written prescriptions and therapeutic indications for antipsychotics, attention-deficit/hyperactivity disorder (ADHD) medications (psychostimulants and nonstimulants), and antidepressants were analyzed in children. Changes in frequency of written prescriptions and therapeutic indications are presented using descriptive statistics. Results: Written prescriptions for antipsychotics decreased by 10% from 2010 to 2016, in contrast to a 114% increase in written prescriptions for antipsychotics observed between 2005 and 2009. Written prescriptions for psychostimulants and antidepressants rose by 35% and 27%, respectively, between 2012 and 2016, comparable with previous results. The most common reasons for recommending an antipsychotic were ADHD and conduct disorder, although there appears to be a downward trend for ADHD compared with other conditions. In contrast, the share of written prescriptions for antipsychotics for autism increased 34% over the study period. Within the second-generation antipsychotics, written prescriptions for aripiprazole increased. An increase in the use of guanfacine extended release for ADHD was also observed. Conclusion: Several factors may be involved in stabilization and small decrease in antipsychotic use in recent years, including physician and patient awareness of adverse effects related to antipsychotic use, knowledge implementation strategies advocating short-term and judicious use of antipsychotics in children, and the approval of guanfacine extended release for use in Canada for ADHD in 2013.

Interest of pharmacoepidemiology in pharmacovigilance: Post-authorization safety studies in regulatory pharmacovigilance activity.

During the past few decades, it has been stated that a paradigm shift has occurred in the assessment and management of patient related drug safety. Some of these changes have resulted in a significant increase in the importance of pharmacoepidemiology and its use in pharmacovigilance. For European member states, the Pharmacovigilance Risk Assessment Committee (PRAC) is responsible for assessing the protocols and results of imposed and non-imposed post-authorization safety studies (PASS). Between 2013 and 2017, the total number of PASS during this 5-years period of the different products, including protocols and results, was 1062. The number of protocols of PASS is increasing over time, except in 2017 where a 25% decrease has been observed. Whereas, PASS results steadily increased over the 5years period. Between 2014 and 2017, about 29% (n=137) of PRAC reviewed protocols were imposed. The number of imposed PASS was almost constant over time with a mean of 34.3±7.6 imposed protocols per year and 3.5±1.74 imposed results per year. The need for the implementation of PASS for pharmacovigilance regulatory activities is increasing. Nevertheless, conducting such studies remains difficult.

Pharmacoepidemiology of Tourette and Chronic Tic Disorders in Sweden 2005-2013.

BACKGROUND: Monitoring "real world" dispensation patterns over time is important to build the evidence base for safe and efficient use of psychotropic drugs. In this study, we aimed to comprehensively examine the patterns of psychotropic drug dispensations in patients with Tourette and chronic tic disorders (TD/CTD) in Sweden between 2005 and 2013. METHODS: A cohort of 6979 TD/CTD patients was identified through the Swedish National Patient Register. Their drug dispensation patterns, collected in the Swedish Prescribed Drug Register, were examined between July 1, 2005 and December 31, 2013. Frequencies of drug dispensations were further stratified by gender and comorbidities. Additionally, differences in the patterns of dispensation in children and adolescents versus adults in the last year of the follow-up were examined, as well as the time trends of the dispensations over the 8-year study period. RESULTS: A total of 5299 (75.9%) TD/CTD patients were dispensed at least one drug during the study period. The most frequently dispensed medications were attention-deficit/hyperactivity disorder (ADHD) drugs (53.8%), antidepressants (50.7%), hypnotics/sedatives (41.7%), and antipsychotics (41.5%). Most of the medicated patients (72.1%) were dispensed more than one drug during the study period. Patterns of dispensation varied according to patient's gender, associated comorbidities, and age group. Dispensation of quetiapine and aripiprazole, antiadrenergics, ADHD drugs, antiepileptics, and hypnotics/sedatives and anxiolytics (particularly the nonbenzodiazepine types) significantly increased over time, whereas dispensation of antidepressants, typical antipsychotics, and benzodiazepine-based anxiolytics significantly decreased over the study period. CONCLUSIONS: Long-term monitoring of these drug dispensation patterns and the study of both their beneficial and adverse effects is warranted.

Serious Adverse Drug Events Reported to the FDA: Analysis of the FDA Adverse Event Reporting System 2006-2014 Database.

BACKGROUND: Data on adverse drug events (ADEs) observed at the population level provide important evidence regarding the safety of a pharmaceutical product in real-world settings. Recent patterns in serious and fatal ADE reporting have not been documented. OBJECTIVE: To assess recent patterns in serious and fatal ADE reports in the United States. METHODS: We conducted a retrospective analysis of the publicly available 2006-2014 FDA Adverse Event Reporting System database. Non-U.S. reports, reports from clinical trials, and reports with missing outcome data were excluded. The annual numbers of ADEs with reported outcome of death, disability, and other serious outcomes were determined. Types (direct, manufacturer expedited, or manufacturer periodic) and sources (consumer, health professional, or other) of these serious ADE reports were also identified. The distribution of serious ADE reports by patient age groups (< 18, 18-44, 45-64, and ≥ 65 years) was determined. Drugs listed as primary suspects in serious ADEs (death, disability, and other serious outcomes) were identified and ranked. Descriptive statistics were used to characterize the patterns in serious or fatal ADE reporting. RESULTS: From 2006 to 2014, the number of serious ADEs reported to the FDA increased 2-fold. A total of 902,323 serious outcomes were reported over the 9-year study period: 244,408 deaths, 72,141 disabilities, and 585,774 other serious outcomes. The relative percentage of reports of deaths was highest during 2012 (32.4%). The percentage of reports of disability was highest during 2006 (12.1%). Overall, the "other serious outcomes" category accounted for almost 65% of serious ADEs reports. Expedited reports from drug manufacturers were most common (about 72%) of the serious ADEs with available data on report type. Health professionals (47.3%) were the most common source of report followed by consumers (36.1%) and other sources (16.6%). A disproportionately high number of reported ADEs was among patients aged 45-64 years (40%) and ≥ 65 years (32.6%). Antineoplastic drugs were more frequently reported with deaths. Three antidepressant drugs were among the top 10 drugs reported with disability. During 2006-2014, there were 38 drugs with more than 1,000 reports of serious ADEs in a given year: 2 drugs currently withdrawn from the market (rofecoxib and parecoxib), 10 drugs with an FDA risk evaluation and mitigation strategies (REMS) program, 13 biologic or specialty drugs, and 14 others. CONCLUSIONS: An overall increase in the trend of the number of serious ADE reports was observed from 2006 to 2014. Drugs with a REMS program and biologic and specialty drugs were involved in a significant number of reported serious ADEs. Data on reporting patterns can guide surveillance and pharmacoepidemiological studies to understand the public health burden of serious ADEs. DISCLOSURES: No outside funding supported this study. Hansen has received consulting fees from and has provided expert testimony for Daichii Sankyo and Takeda. The other authors have nothing to disclose.

Persistencia con estatinas en prevención primaria de enfermedad cardiovascular: resultados en una cohorte de trabajadores españoles / Persistence with statins in primary prevention of cardiovascular disease: findings from a cohort of spanish workers

Introducción y objetivos: El objetivo de este estudio es analizar el patrón de persistencia con estatinas en prevención primaria de enfermedad cardiovascular en una cohorte de trabajadores españoles. Métodos: Este estudio descriptivo se llevó a cabo en el marco del estudio prospectivo longitudinal Aragon Workers'Health Study (n = 5.400). Se identificó a los nuevos usuarios de estatinas varones a partir de datos recogidos en el sistema de información de consumo farmacéutico de Aragón. Se analizaron los patrones de persistencia con estatinas prescritas en prevención primaria cardiovascular, así como los potenciales predictores. Resultados: De los 725 nuevos usuarios de estatinas, menos de un tercio habían persistido durante el año de seguimiento. Alrededor de un 15% de los usuarios no persistentes interrumpieron la terapia con estatinas tras la dispensación de la primera receta y, el 42,1% de ellos no reiniciaron el tratamiento durante el resto del año. La mayor edad (HR = 0,55; IC95%, 0,39-0,77) y el cotratamiento con fármacos antihipertensivos (HR = 0,68; IC95%, 0,56-0,82) redujeron la probabilidad de que se interrumpiera el tratamiento. No se observó asociación entre la persistencia con el tratamiento y la toma concomitante de fármacos antidiabéticos o antitrombóticos, las concentraciones basales de lipoproteínas de baja densidad o las de colesterol total. Sin embargo, la persistencia sí estuvo influida por el tipo de la primera estatina prescrita. Conclusiones: Nuestro análisis en una cohorte de trabajadores varones sanos muestra una baja persistencia con estatinas. Estos resultados reflejan la necesidad de comprender mejor los patrones de utilización de estatinas, especialmente por individuos aparentemente sanos, y de incorporar la conducta del paciente a las decisiones de prescripción (AU)

Introduction and objectives: The aim of this study was to assess patterns of treatment persistence in a cohort of male Spanish workers receiving statin therapy for primary prevention of cardiovascular disease. Methods: This descriptive study was conducted within the framework of the prospective longitudinal Aragon Workers'Health Study (N = 5400). Incident male statin users were identified based on data collected from the regional government's medication consumption information system. Patterns of treatment persistence with statins prescribed for primary cardiovascular disease prevention were assessed and the relevance of potential predictors explored. Results: Among the 725 new statin users, less than one third remained persistent during the 1 year of follow-up. About 15% of nonpersistent users discontinued statin therapy after dispensation of the first prescription; of these, 42.1% did not recommence treatment within the following year. Factors reducing the likelihood of treatment discontinuation were older age (HR, 0.55; 95%CI, 0.39-0.77) and cotreatment with antihypertensive drugs (HR, 0.68; 95%CI, 0.56-0.82). No association was observed between treatment persistence and cotreatment with antidiabetic or antithrombotic drugs, baseline low-density lipoprotein levels, or total cholesterol levels. However, persistence was influenced by the type of statin first prescribed. Conclusions: Our analysis of a cohort of healthy male workers revealed poor statin persistence. These findings underscore the need for a better understanding of patterns of statin use, especially in apparently healthy individuals, and for the incorporation of patient behavior into prescribing decisions (AU)

Pattern of Antidepressant Utilization and Cost in Iran from 2006 to 2013 in Comparison with Other Countries.

Antidepressant prescribing patterns have changed globally over the past few years, with conventional drugs including tricyclic antidepressants and monoamine oxidase inhibitors being replaced by selective serotonin reuptake inhibitors (SSRIs) and novel antidepressants. The objective of this study was to assess antidepressant utilization in Iran from 2006 to 2013 and to show Iran's situation in antidepressant consumption compared with other countries. A cross-sectional study was undertaken using prescription claims data from Iranian insurance agencies. In addition, total antidepressant sales data were obtained from the databank of the national regulatory authority. Medicines were classified according to the Anatomic Therapeutic Chemical (ATC-2012 edition) System. The Organisation for Economic Co-operation and Development data were used to compare national results from Iran with other countries. Antidepressant sales were four-fold higher than those of prescribed antidepressants [24 defined daily doses (DDD)/1000 inhabitants/day were sold whereas 6 DDD/1000 inhabitants/day were prescribed in 2013]. The trend in antidepressant prescriptions and consumption showed increasing use of SSRIs (N06AB). Nortriptyline, fluoxetine, and citalopram accounted for more than 60% of all prescriptions each year. The type of adverse reactions with new expensive antidepressants may seem convincing for the growing tendency toward using these medicines, but considering their high costs, health policymakers have to be aware of the risk of overprescription of newer antidepressant. Drivers of over-the-counter purchase of antidepressants need to be explored.

Hemorragia digestiva y prescripción potencialmente inadecuada de aines en mayores de 65 años / Gastrointestinal bleeding and potentially inappropriate medication by NSAIDs

Fundamentos: Los Antiinflamatorios No Esteroideos (AINE) son un grupo de medicamentos con uso muy extendido en la población, su uso genera un mayor riesgo de hemorragia digestiva. El objetivo de este trabajo fue evaluar y comparar la prescripción potencialmente inadecuada (PPI) de AINE según los criterios de Beers en su versión original con su adaptación española y la relación de esta PPI con los eventos de sangrado gastrointestinal. Métodos: Estudio observacional longitudinal retrospectivo de 12 meses (año 2012) realizado en un área de salud de la Región de Murcia. La población estudiada fue los mayores de 65 años a los que se les había prescrito, al menos, 1 receta médica de AINE durante el periodo de estudio (7.856). Se utilizaron ambas versiones de los criterios de Beers para evaluar la PPI por AINE. Para evaluar el papel etiológico de la exposición a AINE potencialmente inadecuados, respecto a haber recibido AINE, en la hemorragia gastrointestinal se calculó la incidencia acumulada y el Riesgo Relativo. Resultados: La detección de PPI por AINE pasó de 5,6% con la versión original, a 7,0% (DELTA=25,5%; p<0,001) En los sujetos con prescripción de AINE la exposición a PPI por AINE presentó una mayor incidencia de sangrado gastrointestinal pero sin diferencias significativas respecto a la población que recibió AINE (RR=1,6; IC:0,2-14,5). Conclusiones: El uso de la adaptación española de los criterios de Beers posibilita una mayor detección de PPI por AINE en comparación con el uso de la versión original, en ambas versiones, la PPI por AINE no genera un incremento significativo en el sangrado gastrointestinal respecto a recibir AINE

Background: Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) are widely used but they increase the risk of gastrointestinal haemorrage among other adverse effects. The objective of this study was to compare potentially inappropriate medications (PIM) by NSAIDs using the original Beers Criteria, a global reference for evaluating elderly people's prescriptions, and the Spanish adaptation of the same; and the relation between PIM of NSAIDs and gastrointestinal bleeding. Methods: The study was a retrospective observational study carried out located in a primary care district in the province of de Murcia, south-eastern Spain. The study population (n=7.856) were citizens aged 65 and above, with at least one drug prescribed in a Spanish health district during the study period . We analized illnesses and treatments registered in the primary care's electronic medical history of patients and hospital admissions, during the 12 month study period (2012). The original Beers Criteria and their Spanish adaptation were used to evaluate PIM of NSAIDs in patients considering the medication globally and also each active substance. Gastrointestinal bleeding events recorded in the data bases studied were evaluated. Results: Detection of PIM of NSAIDs was 5,6% with the original version and 7,0% (DELTA=25,5%; p<0,001) with the adapted one. PIM of NSAIDs was related with an increased incidence of gastrointestinal bleeding without significant differences between PIM exposed and NSAID exposed patients AINE (RR=1,6; IC:0,2-14,5). Conclusions: The Spanish adaptation of the Beers criteria identified a greater degree of PIM of NSAIDs than the original version, and in both versions the detection of PIM was not related with a significant increase of gastrointestinal bleeding compared to patients exposed to NSAIDs