Analysis of the Financial Impact of Using Cangrelor on the Safety and Efficacy Outcomes in Patients Undergoing Percutaneous Coronary Intervention in Whom Oral Therapy with P2Y12 Inhibitors is Not Feasible or Desirable, in Spain

Purpose: Cangrelor is an intravenous, direct-acting, reversible P2Y12 inhibitor indicated for the reduction of thrombotic cardiovascular events in patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI) in whom oral P2Y12 inhibitors are not feasible or desirable. The objective was to assess the financial impact of introducing cangrelor into the hospital formulary in Spain. Patients and Methods: A budget impact model was developed to calculate the cost difference between two scenarios (without and with cangrelor) to treat CAD patients undergoing PCI in whom oral P2Y12 inhibitors are not feasible or desirable, over 3 years. Intravenous P2Y12 inhibitor (cangrelor), oral P2Y12 inhibitors (clopidogrel, prasugrel, and ticagrelor), and glycoprotein IIb-IIIa inhibitors (GPIs) for bail-out use were considered. Epidemiological, efficacy (thrombotic events including cardiac death), safety (bleeding events), and costs (¿, 2019) data were based on Spanish registries, clinical trials, and meta-analyses. One-way sensitivity analysis established the effect of uncertainty on results. Results: For years 1, 2, and 3, the target population to receive cangrelor was 607, 1,822, and 3,340 patients, and cangrelor uptake was 23.70%, 58.30%, and 51.30%, respectively. The 3-year budget impact was 1,021,717¿ varying from 50,245¿ in year 1 to 599,272¿ in year 3. The results were sensitive to the number of patients treated with GPIs in Spanish hospitals. Conclusion: Based on our results, the financial effort needed to introduce the use of cangrelor in patients undergoing PCI in whom antiplatelet therapy with oral P2Y12 inhibitors is not feasible or desirable barely exceeds one million ¿ over three years, in Spain

Caracterización de los usuarios polimedicados y análisis de la implantación de la receta electrónica

[spa] La polimedicación es una situación frecuente en el ámbito de la atención primaria, sobre todo en pacientes mayores, con enfermedades crónicas y tratamientos complejos, que supone un gran porcentaje del presupuesto en salud de los gobiernos. Por este motivo es importante llevar a cabo estudios que describan los patrones de uso y consumo de medicamentos en esta población, dadas sus características de elevado consumo. Los resultados ayudarán a que la gestión de los sistemas sanitarios sea más racional y se administren mejor los recursos en salud destinados a la población, estableciendo herramientas y mecanismos de control más específicos. En este sentido juegan un papel muy importante las nuevas tecnologías, entre las que se incluye la receta electrónica, desarrollada para favorecer un uso más seguro y eficiente de los medicamentos, entre otras ventajas asistenciales. Este sistema permite integrar los procesos de prescripción y dispensación de la prestación farmacéutica, estableciendo mecanismos de control que favorecen el uso racional del medicamento y aportando información muy importante para el control de los usuarios de mayor riesgo, como sería el caso de los crónicos polimedicados. Esta Tesis es un compendio de 2 artículos indexados (2º cuartil, 1º tercil en la categoría: Medicine, General & Internal) que describen a los usuarios polimedicados de la Región Sanitaria de Barcelona y evalúan la implantación del sistema de receta electrónica en estos pacientes en base a unas variables e indicadores de consumo de medicamentos. En la primera publicación se describe detalladamente a los usuarios polimedicados, en términos de su perfil farmacoterapéutico y el coste que genera su consumo de medicamentos en el sistema público de salud. Cabe destacar que la población evaluada fue de 36.880 usuarios, dato que representó a todos los pacientes polimedicados durante el año 2008 en la Región Sanitaria de Barcelona (edad promedio = 74,5±10,9 años). Esta región representaba aproximadamente el 68% de la población total de Cataluña y concentró el 78% de los usuarios polimedicados de esta Comunidad Autónoma, por lo que este estudio aporta información muy relevante y representativa sobre este grupo de población. El criterio de selección de estos pacientes polimedicados fue un consumo >=16 principios activos diferentes al mes, tratándose pues de una población frágil y altamente polimedicada. El segundo artículo es el primer estudio publicado actualmente que evalúa la introducción de la receta electrónica como herramienta de racionalización del consumo de medicamentos en la población polimedicada. Los resultados sugieren que después de la implantación de la prescripción electrónica en la Región Sanitaria de Barcelona, la racionalidad de la prescripción en pacientes polimedicados mejoró, en términos de número de recetas por usuario y coste por usuario. Este estudio proporciona sin duda un enfoque valioso para una futura evaluación de impacto sobre la implantación de esta nueva tecnología. Para completar ambos trabajos se realizaron revisiones sistemáticas de la literatura, con el objetivo de: 1) Identificar la evidencia disponible sobre la prevalencia y el perfil de usuarios polimedicados, y determinar el número de medicamentos a partir del cual se considera que un usuario es polimedicado; 2) Identificar la evidencia disponible sobre experiencias en las que se relacionase la receta electrónica con polimedicación y/o uso de recursos (análisis de costes o gasto sanitario concretamente).[eng] Polypharmacy is a common situation in primary care setting, specially in the elderly, chronic diseases and complex treatments. It represents a large percentage of governments health budget, so it is important to conduct studies describing the patterns of use and drug consumption in this population. Results will help to better manage resources, establishing tools and mechanisms for more specific control of health systems. In this sense new technologies as electronic prescription play a key role to promote safer and more effective use of medicines, including welfare benefits. This system enables the integration of prescribing and dispensing processes, establishing control mechanisms to promote rational use of medicines and providing valuable information for users in greatest risk, as polymedicated chronic patients. This thesis is a compendium of two indexed articles describing polymedicated users in the Barcelona Health Region and assessing the implementation of electronic prescription in them, based on variables of drug consumption. In the first publication, polymedicated users were described in detail, in terms of therapeutic profile and cost generated by their drug consumption in the public health system. It is noteworthy that the evaluated population was 36,880 users, all polymedicated patients in 2008 in Barcelona Health Region (mean age = 74.5±10.9 years). This region accounted for 68% of the total population of Catalonia and 78% of polymedicated users in this region, so this study provides very important and representative information about this population group. The selection criteria for these patients was consumption of >=16 different drugs/month. The second article is the first published report that evaluates electronic prescribing as a tool that may contribute to rational drug use, particularly in polymedicated patients. Results suggest that after the implementation of electronic prescribing, the rationality of prescribing improved, in terms of number of prescriptions per user and cost per user. This study provides a very valuable approach for future impact assessment. Systematic literature reviews were also conducted to identify the available evidence on: 1) Prevalence and medication profile of polymedicated users, as well as the cut-offs indicating multiple drug use; 2) Electronic prescribing related to polypharmacy and health expenditure or cost analysis

The burden of perioperative hypertension/hypotension: A systematic review

Study objective: Our goal is to review the outcomes of acute hypertensive/hypotensive episodes from articles published in the past 10 years that assessed the short- and long-term impact of acute hypertensive/hypotensive episodes in the perioperative setting. Methods: We conducted a systematic peer review based upon PROSPERO and Cochrane Handbook protocols. The following study characteristics were collected: study type, author, year, population, sample size, their definition of acute hypertension, hypotension or other measures, and outcomes (probabilities, odds ratio, hazard ratio, and relative risk) and the p-values; and they were classified according to the type of surgery (cardiac and non-cardiac). Results: A total of 3,680 articles were identified, and 66 articles fulfilled the criteria for data extraction. For the perioperative setting, the number of articles varies by outcome: 20 mortality, 16 renal outcomes, 6 stroke, 7 delirium and 34 other outcomes. Hypotension was reported to be associated with mortality (OR 1.02-20.826) as well as changes from the patient's baseline blood pressure (BP) (OR 1.02-1.36); hypotension also had a role in the development of acute kidney injury (AKI) (OR 1.03-14.11). Postsurgical delirium was found in relation with BP lability (OR 1.018-1.038) and intra- and postsurgical hypotension (OR 1.05-1.22), and hypertension (OR 1.44-2.34). Increased OR (37.67) of intracranial hemorrhage was associated to postsurgical systolic BP >130 mmHg. There was a wide range of additional diverse outcomes related to hypo-, hypertension and BP lability. Conclusions: The perioperative management of BP influences short- and long-term effects of surgical procedures in cardiac and non-cardiac interventions; these findings support the burden of BP fluctuations in this setting

Effects of the Off-Label Drug Prescription in the Paediatric Population in Spain from the Adoption of the Latest European Regulation: A Pre-Post Study

The year 2021 marks the 15th anniversary of the Paediatric Regulation (1901/2006/EC) in Europe. The main aim of the study was to conduct a pre-post comparison on the annual off-label prescription rates in the under-18 population in Spain and assess the potential influence of the Paediatric Regulation adoption. An observational study in the paediatric population was performed. Four cross-sectional annual periods, one before and the three latest periods after the adoption of the Regulation, were compared. Prescriptions in the primary health care setting were sorted by age group and drug and off-label status were determined. The number of off-label prescriptions issued by paediatricians was over two million per year. Prior to the adoption of the Paediatric Regulation, the off-label prescription rate was estimated at 7% of total prescriptions. Although the increase in the off-label rate over the study periods was mild, it was statistically significant (OR: 1.045; 95% CI: 1.043-1.046; p < 0.05). One of the most vulnerable population groups was neonates and infants up to 1 year, in which the off-label prescription rates showed the highest increase during the post follow-up period, which was statistically significant (OR: 4.270; 95% CI: 4.253-4.287; p < 0.05). The findings can help raise awareness and advocate for the development and authorization of medicines for children in the primary health care setting. Keywords: off-label prescription, paediatrics, paediatric regulation, pharmaceutical products, prescription drugs, primary health car

Prevention strategies to identify LASA errors: building and sustaining a culture of patient safety

Background: Potential look-alike, sound-alike (LASA) errors in outpatient and inpatient prescriptions have been widely described worldwide. However, most strategies of reducing drug name confusion have been only focused on the processes of prescribing and dispensing, often following local rules. Main text: An illustrative recent example about this topic is given: the antidepressant Brintellix® (vortioxetine)(Takeda Pharmaceuticals USA, Inc.) and the antiplatelet medication Brilinta® (ticagrelor) (AstraZeneca LP). Revision of the initiatives that are currently applied to prevent potential LASA errors in different countries around the world and debate about the emerging strategies that could be implemented in short and mid-term. At present, a common policy worldwide on the authorization of unique names for innovative medicines does not exist. The implication of authorities in topdown strategies and the importance of developing an international health policy on the authorization of unique names for innovative medicines are highlighted in the following piece of opinion. Conclusions: Building and sustaining a culture of patient safety should be considered as a global top-down strategy which involved all the elements in the system (regulatory bodies, manufacturers and suppliers). The precedent established by the FDA in prevention strategies to identify and avoid LASA errors has been extremely important and should lead to international discussion. Coordinated international efforts are urgently needed in this area for the sake of patients' safety

Utilización de recursos sanitarios y costes asociados al diagnóstico y tratamiento de cada episodio de trombosis venosa profunda y sangrado en pacientes intervenidos de cirugía ortopédica de cadera o rodilla

Objective: To determine the use of healthcare resources and costs associated with the diagnosis and treatment of thrombosis and bleeding patients who have undergone elective hip or knee replacement surgery, in routine clinical practice conditions. Patients and methods: This multicentre observational and retrospective study extracted data from the medical records of three Spanish public hospitals (2010). Patients ≥40 years who had received prophylaxis-anticoagulation were included. They were randomised into three groups: (a) control (no hospital complications), (b) bleeding, and (c) thrombosis. General variables, use of resources and costs were analysed. Statistical analysis: logistic regression and ANCOVA for model correction (P < .05) was included. Results: A total of 141 patients (control: 60; bleeding: 60; and thrombosis: 21), with a mean age 68.7 (SD: 10.4) years, and 68.1% females were identified. Hip arthroplasty was more frequent (71.6%). The bleeding risk was associated with age (OR = 1.1) and thrombosis with COPD (OR = 1.8); P < .05). The average length of stay for the thrombosis, bleeding and control groups was 13.9, 11.5 and 7.4 days, respectively; P < .001). The total costs for each group were D10,484.3; D8766.4 and D6496.1 respectively; P < .05. All grouped results were comparable between them according to the hospital analysed and the type of replacement. Conclusions: Costs were higher for thrombosis and bleeding patients, respectively. Costs were associated with length of stay and hospital-acquired infections.Objetivo: Conocer la utilización de recursos sanitarios y los costes asociados al diagnóstico y tratamiento de la trombosis y sangrado en pacientes intervenidos de artroplastia primaria total de cadera (ATC) o rodilla (ATR), durante 3 meses de seguimiento. Pacientes y método: Estudio observacional de carácter multicéntrico y retrospectivo, realizado a partir de los registros médicos de pacientes pertenecientes a 3 centros hospitalarios-públicos espanoles ˜ (ano˜ 2010). Se consideraron aleatoriamente 3 grupos de pacientes: a) control (sin complicaciones hospitalarias); b) sangrado, y c) trombosis. Se incluyeron variables generales, de utilización de recursos y sus costes. Análisis estadístico: regresión logística y ANCOVA, p < 0,05. Resultados: Se incluyeron pacientes ≥ 40 anos ˜ y que hubieran recibido profilaxis anticoagulante. Se incluyó un total de 141 pacientes (control: 60; sangrado: 60; y trombosis: 21). La edad media fue de 68,7 (DE: 10,4) anos ˜ y el 68,1% fueron mujeres. La ATR fue la técnica más frecuente (71,6%). El riesgo de sangrado se relacionó con la edad (OR = 1,1) y el de trombosis con la EPOC (OR = 1,8), p < 0,05. El promedio de días de estancia de los grupos de trombosis, sangrado y control fue de 13,9; 11,5 y 7,4 días, respectivamente, p < 0,001). Los costes totales fueron: 10.484,3 D; 8.766,4 D, y 6.496,1 D, respectivamente, p < 0,05. Todos los resultados agrupados fueron comparables entre ellos según el hospital analizado y el tipo de artroplastia. Conclusiones: Los costes más elevados se producen en los pacientes que habían desarrollado una trombosis y sangrado, respectivamente. Los costes se relacionaron con la prolongación de los días de estancia y las infecciones intrahospitalariasMedicin

Off-label use of fixed-dose combination of tramadol and dexketoprofen in primary health care. Evidence-based or cause for concern?

Introduction: The use of the fixed-dose combination of tramadol/dexketoprofen in Spain and in other countries has increased considerably. The authorized therapeutic indication for this medicinal product is the short-term symptomatic treatment of moderate to severe acute pain in adult patients. The objective of this study was to describe the pattern of use of tramadol/dexketoprofen in the field of primary health care. Method: A cross-sectional, descriptive and multicenter study was carried out. The study population included all patients from a Primary Care Department (53 Primary Care teams) with an active prescription of tramadol/dexketoprofen on March 28, 2018. The target population was those patients who were prescribed tramadol/dexketoprofen. dexketoprofen for >20 days. Results: A total of 176 patients had an active prescription for tramadol/dexketoprofen. All patients (100%) had a duration of treatment greater than 5 days and 72.7% (N=128) greater than 20 days. The mean duration of treatment was 14±160.9 days in patients who had less than 20 days of treatment and 224±160.8 days in patients who had more than 20 days of treatment. 35.1% of the patients were treated with >2 pain medications and concomitantly with tramadol/dexketoprofen. The general practitioner initiated 65.6% of the prescriptions. Conclusions: The fixed-dose combination of tramadol/dexketoprofen was frequently used off-label, according to the product characteristics and the available scientific evidence. This study warns about the potential risks associated with the use of this drug in clinical practice, such as lack of effectiveness and/or the appearance of adverse effects

Off-label use of fixed-dose combination of tramadol and dexketoprofen in primary health care. Evidence-based or cause for concern?

Introduction: The use of the fixed-dose combination of tramadol/dexketoprofen in Spain and in other countries has increased considerably. The authorized therapeutic indication for this medicinal product is the short-term symptomatic treatment of moderate to severe acute pain in adult patients. The objective of this study was to describe the pattern of use of tramadol/dexketoprofen in the field of primary health care. Method: A cross-sectional, descriptive and multicenter study was carried out. The study population included all patients from a Primary Care Department (53 Primary Care teams) with an active prescription of tramadol/dexketoprofen on March 28, 2018. The target population was those patients who were prescribed tramadol/dexketoprofen. dexketoprofen for >20 days. Results: A total of 176 patients had an active prescription for tramadol/dexketoprofen. All patients (100%) had a duration of treatment greater than 5 days and 72.7% (N=128) greater than 20 days. The mean duration of treatment was 14±160.9 days in patients who had less than 20 days of treatment and 224±160.8 days in patients who had more than 20 days of treatment. 35.1% of the patients were treated with >2 pain medications and concomitantly with tramadol/dexketoprofen. The general practitioner initiated 65.6% of the prescriptions. Conclusions: The fixed-dose combination of tramadol/dexketoprofen was frequently used off-label, according to the product characteristics and the available scientific evidence. This study warns about the potential risks associated with the use of this drug in clinical practice, such as lack of effectiveness and/or the appearance of adverse effects

Indirect costs associated with skin infectious disease in children: a systematic review

Background: There are limited data in the literature on the indirect costs associated with skin and soft tissue infections (SSTIs) in the pediatric population. This study aimed to conduct a systematic review of the indirect costs associated with SSTIs in children. Methods: The search was conducted in PubMed, SCOPUS, and Web of Science up to January 2020. Thirteen search strategies were designed combining MeSH terms and free terms. SSTIs were defined as bacterial or viral infections, dermatomycoses, and parasitic infestations. Only primary studies were included. All analyzed costs were converted to 2020 Euros. Results: Thirteen of the identified publications presented indirect costs of SSTIs in children and were conducted in Argentina, Australia, Brazil, Hungary, New Zealand, Poland, Spain, Taiwan, and the USA. Nine studies described indirect costs associated with infection of Varicella-zoster virus: lost workdays by outpatient caregivers ranged from 0.27 to 7.8, and up to 6.14 if caring for inpatients; total productivity losses ranged from 1.16 to 257.46 per patient. Three studies reported indirect costs associated with acute bacterial SSTIs (community-associated methicillinresistant Staphylococcus aureus) in children: total productivity losses ranged from 1,814.39 to 8,224.06 per patient, based on impetigo, cellulitis, and folliculitis. One study of parasitic infestations (Pediculus humanus capitis) reported total indirect costs per patient of 68.57 (formal care) plus 21.41 due to time lost by parents in purchasing treatment. Conclusions: The economic burden of SSTIs is highly relevant but underestimated due to the lack of studies reporting indirect costs. Further cost studies will allow a better understanding of the magnitude of the financial burden of the disease. Keywords: Skin infectious diseases, Cost of illness, Indirect costs, Child, SSTIs, Systematic revie