Medicamentos de alto impacto económico y sanitario en la prestación farmacéutica hospitalaria / Medicines with high economic impact in the hospital setting

Objetivos: Los medicamentos de alto impacto económico (MAIE) constituyen un reto para los servicios de salud públicos de los países europeos. Sin embargo, no existe consenso sobre qué constituye un MAIE. El objetivo del estudio fue configurar una lista de MAIE dispensados por los servicios de farmacia hospitalarios y analizar la situación respecto a estos fármacos en España.Métodos: Se consideraron MAIE aquellos fármacos con un coste >10.000 €/año (MAC) o con un elevado volumen de consumo (MEC). Se estimaron los precios (PVL) por dosis diaria definida o dosis diaria prescrita.Resultados: Un total de 147 principios activos fueron considerados MAC, correspondiendo mayoritariamente con los grupos: L (69,4%), J (10,9%) y A (10,2%). El PVL medio diario de los MAC fue 218,6 € (28,6-2.892,5). El 38,8% de los MAC fueron innovadores, 26,5% huérfanos y 34,0% biológicos. Dieciséis medicamentos tuvieron un coste >10.000 €/envase. Los MEC pertenecieron principalmente al grupo L (45,0%) y J (35,0%). El PVL medio diario de los MEC fue 154,4 € (1,1-1.629,3). El 35,5% fueron innovadores, 5,0% huérfanos y 60,0% biológicos.Conclusiones: Un elevado número de MAIE son dispensados por los servicios de farmacia hospitalarios, principalmente antineoplásicos y antiinfecciosos. Aunque el PVL mínimo diario para considerar un medicamento de alto impacto es 27,4 €, el PVL medio diario de los MAC fue >200 €. Sin embargo, el elevado consumo de algunos fármacos, hace que medicamentos con un coste tan bajo como 1,1 € puedan ser considerados MAIE. Se puede establecer una nueva categoría de MAC para aquellos con un coste >10.000 €/envase. (AU)

Objetivos: Los medicamentos de alto impacto económico (MAIE) constituyen un reto para los servicios de salud públicos de los países europeos. Sin embargo, no existe consenso sobre qué constituye un MAIE. El objetivo del estudio fue configurar una lista de MAIE dispensados por los servicios de farmacia hospitalarios y analizar la situación respecto a estos fármacos en España.Métodos: Se consideraron MAIE aquellos fármacos con un coste >10.000 €/año (MAC) o con un elevado volumen de consumo (MEC). Se estimaron los precios (PVL) por dosis diaria definida o dosis diaria prescrita.Resultados: Un total de 147 principios activos fueron considerados MAC, correspondiendo mayoritariamente con los grupos: L (69,4%), J (10,9%) y A (10,2%). El PVL medio diario de los MAC fue 218,6 € (28,6-2.892,5). El 38,8% de los MAC fueron innovadores, 26,5% huérfanos y 34,0% biológicos. Dieciséis medicamentos tuvieron un coste >10.000 €/envase. Los MEC pertenecieron principalmente al grupo L (45,0%) y J (35,0%). El PVL medio diario de los MEC fue 154,4 € (1,1-1.629,3). El 35,5% fueron innovadores, 5,0% huérfanos y 60,0% biológicos.Conclusiones: Un elevado número de MAIE son dispensados por los servicios de farmacia hospitalarios, principalmente antineoplásicos y antiinfecciosos. Aunque el PVL mínimo diario para considerar un medicamento de alto impacto es 27,4 €, el PVL medio diario de los MAC fue >200 €. Sin embargo, el elevado consumo de algunos fármacos, hace que medicamentos con un coste tan bajo como 1,1 € puedan ser considerados MAIE. Se puede establecer una nueva categoría de MAC para aquellos con un coste >10.000 €/envase. (AU)

Update on the perioperative management of antiplatelets and anticoagulants in ophthalmic surgery.

INTRODUCTION: Anti-thrombotic drugs (antiplatelets and anticoagulants) are widely used for different clinical reasons. This means that there are an increasing number of patients undergoing elective ophthalmic surgery that are being treated with these drugs. A better knowledge of their implications and their peri-operative use may help to prevent surgical and secondary adverse events. There is often no firm recommendation on how to manage certain drugs in certain surgeries. OBJECTIVE: To review the recommendations in the scientific literature as regards managing anti-thrombotic agents during the peri-operative period of ophthalmic surgery. MATERIAL AND METHODS: A review was made of the relevant guidelines and studies using an antiplatelet and anticoagulant drugs approach for cataract, vitreo-retinal, glaucoma, oculoplastic, and strabismus surgeries. RESULTS: Recommendations about whether to continue or discontinue anti-thrombotic drugs in the peri-operative period of different ophthalmic surgical fields are presented. CONCLUSIONS: There are only firm recommendations of maintaining anti-thrombotic drugs as regards cataract surgery using phacoemulsification with topical anaesthesia. In other surgical fields, ophthalmologists should balance the risk of thromboembolic events and risks of haemorrhagic complications in order to carry out a proper management. A multi-disciplinary approach is recommended for complex cases. Additional studies should be performed to better characterise the peri-operative use of anti-thrombotic agents in order to prepare clinical guidelines for ophthalmic surgery.

Actualización en el manejo perioperatorio de antiagregantes y anticoagulantes en cirugía oftalmológica / Update on the perioperative management of antiplatelets and anticoagulants in ophthalmic surgery

Introducción Los fármacos anticoagulantes y antiagregantes son ampliamente utilizados con indicaciones médicas diversas. Por tanto, hay cada vez más pacientes que precisan una cirugía oftalmológica programada y se encuentran en tratamiento con esta medicación. El conocimiento de sus implicaciones y su correcto abordaje perioperatorio permite reducir complicaciones quirúrgicas y efectos adversos en los pacientes. En muchas ocasiones no hay una recomendación clara sobre cómo actuar con estas familias de fármacos en determinadas cirugías. Objetivo Realizar una revisión bibliográfica sobre el manejo perioperatorio de los antiagregantes y anticoagulantes en cirugía oftalmológica. Material y métodos Se revisan los protocolos y la literatura existente acerca del empleo de dichos fármacos en diversas cirugías oftálmicas: catarata, vítreo-retina, glaucoma, cirugía oculoplástica y orbitaria y estrabismo. Resultados Se referencian guías clínicas y estudios que recogen las recomendaciones acerca del mantenimiento o suspensión de antiagregantes y anticoagulantes en diferentes campos quirúrgicos de la oftalmología. Conclusiones En la cirugía de catarata mediante facoemulsificación con anestesia tópica existe evidencia de que el mantenimiento de la medicación antitrombótica es seguro. En el resto de las cirugías oftalmológicas se debería actuar en función del riesgo hemorrágico y trombótico que presente la cirugía y el paciente para su correcta utilización. En casos complejos, se recomienda un abordaje multidisciplinar. Serían necesarios más estudios para la confección de guías clínicas que facilitasen el manejo perioperatorio de estos fármacos en cirugía oftalmológica (AU)

Introduction Anti-thrombotic drugs (antiplatelets and anticoagulants) are widely used for different clinical reasons. This means that there are an increasing number of patients undergoing elective ophthalmic surgery that are being treated with these drugs. A better knowledge of their implications and their peri-operative use may help to prevent surgical and secondary adverse events. There is often no firm recommendation on how to manage certain drugs in certain surgeries. Objective To review the recommendations in the scientific literature as regards managing anti-thrombotic agents during the peri-operative period of ophthalmic surgery. Material and methods A review was made of the relevant guidelines and studies using an antiplatelet and anticoagulant drugs approach for cataract, vitreo-retinal, glaucoma, oculoplastic, and strabismus surgeries. Results Recommendations about whether to continue or discontinue anti-thrombotic drugs in the peri-operative period of different ophthalmic surgical fields are presented. Conclusions There are only firm recommendations of maintaining anti-thrombotic drugs as regards cataract surgery using phacoemulsification with topical anaesthesia. In other surgical fields, ophthalmologists should balance the risk of thromboembolic events and risks of haemorrhagic complications in order to carry out a proper management. A multi-disciplinary approach is recommended for complex cases. Additional studies should be performed to better characterise the peri-operative use of anti-thrombotic agents in order to prepare clinical guidelines for ophthalmic surgery (AU)

Added prognostic value of longitudinal changes of angiogenic factors in early-onset severe pre-eclampsia: a prospective cohort study.

OBJECTIVE: To assess in women with early-onset severe pre-eclampsia whether longitudinal changes in angiogenic factors improve the prediction of adverse outcome. DESIGN: Prospective cohort study. SETTING: Maternity units in two Spanish hospitals. POPULATION: Women with diagnosis of early-onset severe pre-eclampsia. METHODS: Levels of placental growth factor (PlGF), soluble fms-like tyrosine kinase (sFlt-) and sFlt-1/PlGF ratio were measured at admission and before delivery, and average daily change calculated. The association of longitudinal changes of angiogenic factors with the time interval to delivery and with complications was evaluated by logistic and Cox regression. MAIN OUTCOME MEASURES: Interval to delivery and composite of adverse outcomes. RESULTS: We included 63 women, of which 26 (41.3%) had a complication. Longitudinal changes of sFlt-1 were more pronounced in complicated pregnancies (median: 1047 versus 342 pg/ml/day; P = 0.04). On the multivariate analysis, the clinical risk score and sFlt-1 at admission explained 6.2% of the uncertainty for complication; the addition of sFlt-1 longitudinal changes improved this to 25.3% (P = 0.002). The median time from admission to delivery was 4 days (95% CI 1.6-6.04) in those in the highest quartile of sFlt-1 longitudinal changes versus 16 days (95% CI 12.4-19.6) in the remaining women (Log-rank test P < 0.001). CONCLUSIONS: Longitudinal changes in sFlt-1 maternal levels from admission for confirmed early-onset severe pre-eclampsia add to baseline characteristics in the prediction of adverse outcome and interval to delivery. TWEETABLE ABSTRACT: In early-onset severe pre-eclampsia, longitudinal changes in sFlt-1 levels improve the prediction of complications and interval to delivery.

Diabetic retinopathy in well-controlled type 2 diabetes: Role of glycaemic memory.

AIMS: As diabetic retinopathy (DR) can occur even in well-controlled patients with type 2 diabetes (T2D), our study sought to determine whether it might be related to 'glucose memory' by evaluating patients' HbA1c over previous years and their skin autofluorescence (SAF). METHODS: In 334 patients with T2D and HbA1c levels≤8%, their available values of HbA1c from previous years were collected, and their SAF measured by an advanced glycation end-product (AGE) reader. Binary logistic regression analysis was then used to correlate DR with previously recorded HbA1c levels and to SAF, with adjustment for DR risk factors [age, gender, BMI, duration of diabetes, arterial hypertension, diabetic kidney disease (DKD), blood lipid levels and statin treatment]. RESULTS: Our patients were mostly men (58.4%) aged 63±10years, with a duration of diabetes of 13±10years and HbA1c=7.1±0.7%. Of these patients, 84 (25.1%) had DR, which was associated with longer duration of diabetes and greater prevalence of DKD. A total of 605 HbA1c values from previous years were collected for time periods -4±3 months (n=255), -16±4months (n=152), -30±4months (n=93) and -62±26 months (n=105). After adjustment, the association between DR and having an HbA1c higher than the median was significant only for the oldest previous HbA1c values: OR=6.75, 95% CI: 1.90-23.90. Moreover, SAF values were higher in those with DR [2.95±0.67 arbitrary units (AU)] vs 2.65±0.65 AU with no DR (P<0.01) and were also associated with the oldest previous HbA1c values (P<0.01). CONCLUSION: Our study found that 25.1% of our well-controlled T2D patients had DR, which was related to both their HbA1c levels from 5years prior to study admission and their SAF values, a marker of glucose memory.

Innate immunity during SARS-CoV-2: evasion strategies and activation trigger hypoxia and vascular damage.

Innate immune sensing of viral molecular patterns is essential for development of antiviral responses. Like many viruses, SARS-CoV-2 has evolved strategies to circumvent innate immune detection, including low cytosine-phosphate-guanosine (CpG) levels in the genome, glycosylation to shield essential elements including the receptor-binding domain, RNA shielding and generation of viral proteins that actively impede anti-viral interferon responses. Together these strategies allow widespread infection and increased viral load. Despite the efforts of immune subversion, SARS-CoV-2 infection activates innate immune pathways inducing a robust type I/III interferon response, production of proinflammatory cytokines and recruitment of neutrophils and myeloid cells. This may induce hyperinflammation or, alternatively, effectively recruit adaptive immune responses that help clear the infection and prevent reinfection. The dysregulation of the renin-angiotensin system due to down-regulation of angiotensin-converting enzyme 2, the receptor for SARS-CoV-2, together with the activation of type I/III interferon response, and inflammasome response converge to promote free radical production and oxidative stress. This exacerbates tissue damage in the respiratory system, but also leads to widespread activation of coagulation pathways leading to thrombosis. Here, we review the current knowledge of the role of the innate immune response following SARS-CoV-2 infection, much of which is based on the knowledge from SARS-CoV and other coronaviruses. Understanding how the virus subverts the initial immune response and how an aberrant innate immune response contributes to the respiratory and vascular damage in COVID-19 may help to explain factors that contribute to the variety of clinical manifestations and outcome of SARS-CoV-2 infection.

Serum fructosamine predicts macrosomia in well-controlled hyperglycaemic pregnant women: An observational cross-sectional study.

AIM: While serum fructosamine may be a good marker of glucose control in pregnant women with diabetes, its relationship with macrosomia is still uncertain. METHODS: In 130 hyperglycaemic women with singleton pregnancies (117 gestational diabetes mellitus, 13 pregestational diabetes), serum fructosamine and HbA1c levels were measured at 25±7 weeks of gestation. Levels in mothers of infants with and without macrosomic newborns (birth weight>4000g and/or large-for-gestational-age birth weight>90th percentile) were compared using logistic regression analysis adjusted for macrosomia risk factors. RESULTS: These 130 pregnant women were 33±5 years old; their BMI before pregnancy was 27.7±6.9kg/m2, and they gained 7.5±5.1kg during the first 6 months of gestation. Glucose control was good according to HbA1c levels (5.3±0.3%; 34±2mmol/mol), yet 17/130 (13%) newborns had macrosomia: 3900±227g vs 3057±512g (P<0.001) in the others. These mothers were older and had higher parity, whereas their BMI scores before pregnancy and gestational weight gains did not differ. Fructosamine levels were also higher at 221±40µmol/L vs 192±22µmol/l (P<0.001), respectively, and remained significant even after adjusting for maternal age, BMI, parity, type of diabetes, antecedents of macrosomia and excessive gestational weight gain. By contrast, HbA1c did not differ between the two groups. In fact, nearly two-thirds (64.7%) of the mothers of macrosomic newborns had fructosamine levels>200µmol/l vs 31.9% of mothers with non-macrosomic newborns (P<0.05). CONCLUSION: High fructosamine levels are associated with macrosomia in the newborns of well-controlled hyperglycaemic pregnant women.

Association of childhood trauma and genetic variability of CRH-BP and FKBP5 genes with suicidal behavior in bipolar patients.

BACKGROUND: Around 8% of bipolar disorder (BD) patients die by suicide every year, accounting for the highest rate among the psychiatric population. Suicidal behavior (SB) is mediated by an intertwining system of extrinsic and intrinsic factors. Childhood trauma (CT) and gene variants of the stress-management hypothalamic-pituitary-adrenal (HPA) axis have been reported as risk factors for SB. The aim of this study was to elucidate the association of CT and HPA axis genetic variants with SB. METHODS: 135 BD patients were recruited for clinical assessment of CT and SB by means of the Childhood Trauma Questionnaire (CTQ) and the Columbia Suicide Severity Rating Scale (C-SSRS), respectively. A total of 28 single nucleotide polymorphisms (SNPs) from 8 HPA axis genes (POMC, NR3C2, CRH-BP, NR3C1, FKBP5, CRHR2, CRHR1, and MC2R) were genotyped. RESULTS: The analyses showed an association of total CTQ score (p = 0.003), emotional abuse (p = 0.001), sexual abuse (p = 0.005) and emotional neglect (p = 0.005) with SB. CRH-BP rs7728378-C carriers (p = 0.004; OR = 3.05), FKBP5 rs3777747-AA (p = 0.039; OR = 0.34) and FKBP5 rs2766533-GG genotypes (p = 0.001; OR = 2.93) were associated with SB although only rs2766533 survived multiple test correction. No gene-environment interaction was found. LIMITATIONS: The relatively small sample size limits the statistical power to detect smaller environmental and genetic effects. Cross-sectional data collection in psychometric assessments can yield biased data. CONCLUSIONS: The present study characterizes novel SB risk factors and replicates previous findings in BD patients. CT and variability in CRH-BP and FKBP5 genes should be further studied for a better understanding of SB and ultimately help in suicide prevention.