El fentanilo como punto de partida en la crisis de opioides. Situación actual y visión retrospectiva en Europa y EEUU / Fentanyl as a starting point in the opioid crisis. Current situation and retrospective view in Europe and the USA

El fentanilo, un fármaco opioide sintetizado en 1960 de elevada potencia analgésica y amplia utilidad terapéutica, se ha convertido en la principal causa de muerte por sobredosis de drogas en los EEUU. Los datos provisionales de fallecidos por sobredosis de drogas en 2021 ofrecen la escalofriante cifra de 108.000 muertos, en una tendencia fuertemente ascendente desde hace una década. En Europa los fallecidos por sobredosis de drogas en 2020 (6.400) también aumentaron ligeramente respecto a 2019, aunque no específicamente relacionadas con el fentanilo. Tanto en Europa como en EEUU, aproximadamente el 75% de las sobredosis de drogas con resultado mortal están relacionadas con los opioides. En EEUU particularmente con el fentanilo y los análogos del fentanilo fabricados ilícitamente, y en Europa con la heroína. Aunque con diferentes matices epidemiológicos, la crisis de opioides es un fenómeno global que se ha superpuesto con carácter de pandemia a la reciente crisis sanitaria mundial por COVID-19. La tasa de mortalidad relacionada con los opioides sintéticos (particularmente con el fentanilo) crece exponencialmente de forma imparable. Esto ocurre de una manera muy pronunciada en EEUU desde el año 2013, pero también en Europa desde el año 2017, aunque con menor impacto. De alguna forma podríamos entender al fentanilo como un punto de partida en la crisis de opioides, puesto que el fenómeno es dinámico y cambiante. Para comprender mejor la epidemia de opioides resulta necesario saber que a medida que son fiscalizadas las sustancias relacionadas con el fentanilo, nuevos opioides sintéticos (NSO) sin uso médico aprobado (como por ejemplo los llamados ‘nitacenos’) son detectados cada vez con mayor frecuencia en las incautaciones de drogas e informes forenses y toxicológicos en todo el mundo

Fentanyl, an opioid drug synthesized in 1960 with high analgesic potency and broad therapeutic utility, has become the leading cause of drug overdose death in the United States. Provisional data on drug overdose deaths in 2021 offer the chilling figure of 108.000 deaths, in a strongly upward trend for a decade. In Europe, drug overdose deaths in 2020 (6.400) also increased slightly compared to 2019, although not specifically related to fentanyl. In both Europe and the US, approximately 75% of fatal drug overdoses are related to opioids. In the US particularly with illicitly manufactured fentanyl and fentanyl analogues, and in Europe with heroin. Although with different epidemiological nuances, the opioid crisis is a global phenomenon that has been superimposed as a pandemic on the recent global health crisis due to COVID-19. The mortality rate related to synthetic opioids (particularly fentanyl) is growing exponentially and unstoppably. This has occurred in a very pronounced way in the US since 2013, but also in Europe since 2017, although with less impact. In some way we could understand fentanyl as a starting point in the opioid crisis, since the phenomenon is dynamic and changing. To better understand the opioid epidemic, it is necessary to know that as substances related to fentanyl are controlled, new synthetic opioids (NSO) without approved medical use (such as the so-called ‘nitazenes’) are detected with increasing frequency. in drug seizures and forensic and toxicology reports worldwide. (AU)

Patient benefit as a goal of humanization.

Patient empowerment is one of the main pillars of humanisation. Therefore, consideration of patients' preferences and expectations should be  taken into account during the practice of any healthcare professional.  Improving overall survival and quality of life are the main wishes of patients.  Indeed, the recent emergence of Patient Reported Outcomes has become an important focus for healthcare providers. The hospital pharmacist  specialised in drug evaluation is a professional who evaluates the efficacy,  safety, appropriateness and efficiency of treatments prescribed by physicians, and decision-making must be based on both technical factors and  the four principles of bioethics. The correct application of evidence-based  clinical practice allows to provide patients with increases in survival and/or quality of life, adapting the convenience and costs to the current  situation. With this in mind, it could be said that the evaluation of medicines  involves a strong commitment to humanisation. On the other hand,  rganisations that promote the rigorous evaluation and selection of medicines  stand as allies of patients, as they have a direct impact on them and an  indirect impact on society. Regulatory agencies in charge of approving and  financing medicines in healthcare systems play a key role in the process of humanising clinical decision-making and empowering patients. If  these agencies approve the use of new medicines based on data that do not measure quality of life or survival of patients when there are already other therapeutic alternatives for these pathologies, they are indirectly failing  to meet patients' expectations and are infringing bioethical principles. This can  have a considerable influence on the benefit-risk ratio of drugs, and  patients  may be treated with regimens that do not provide benefit, or may even harm  them. Therefore, where should the process of humanisation be oriented? It  seems reasonable that the benefit of the patient should be the fundamental  objective of the process of humanisation of healthcare, evidently.

El empoderamiento del paciente supone uno de los principales pilares de la  humanización. Por ello, la consideración de las preferencias y expectativas de  los pacientes debería ser tenida en cuenta durante el ejercicio de cualquiera de  los profesionales de la salud. Mejorar la supervivencia global y la calidad de  vida son los deseos principales de los pacientes. De hecho, la reciente  aparición de los llamados Patient Reported Outcomes ha supuesto un  importante foco para los agentes involucrados en la asistencia sanitaria. El  farmacéutico hospitalario especializado en la evaluación de medicamentos es  un profesional que evalúa la eficacia, seguridad, adecuación y eficiencia de los  tratamientos prescritos por facultativos, y debe basar la toma de decisiones  tanto en factores técnicos como en los cuatro principios bioéticos. La correcta  aplicación de la práctica clínica basada en la evidencia permite proveer a los  pacientes de incrementos de supervivencia y/o calidad de vida, adecuando la  conveniencia y costes a la situación actual. Teniendo en cuenta esto, podría  decirse que la evaluación de medicamentos supone un fuerte compromiso con  la humanización. Por otra parte, las organizaciones que promueven la  evaluación y selección de medicamentos rigurosamente se erigen como aliados  de los pacientes, ya que repercuten de forma directa en éstos y de  forma indirecta en la sociedad. Las agencias reguladoras encargadas de la  aprobación y financiación de medicamentos en los sistemas sanitarios  protagonizan un papel fundamental en el proceso de humanización de la toma  de decisiones clínicas y empoderamiento de pacientes, ya que si aprueban el  uso de nuevos medicamentos según datos que no miden la calidad de vida o  supervivencia de los pacientes cuando ya existen otras alternativas  terapéuticas para estas patologías, indirectamente no estarán dando respuesta a las expectativas de los pacientes y conculcarán los principios bioéticos. Esto puede tener una considerable influencia en la relación beneficio-riesgo de los  fármacos, pudiendo tratar a pacientes con esquemas que no aportan beneficio,  o incluso podrían perjudicarles. Por tanto, ¿hacia dónde debiera ir  orientado el proceso de humanización? Parece razonable que el beneficio del  paciente sea el objetivo fundamental del proceso de humanización de la  asistencia sanitaria, evidentemente.

El beneficio del paciente como objetivo de la humanización / Patient benefit as a goal of humanization

El empoderamiento del paciente supone uno de los principales pilares dela humanización. Por ello, la consideración de las preferencias y expectativas de los pacientes debería ser tenida en cuenta durante el ejerciciode cualquiera de los profesionales de la salud. Mejorar la supervivenciaglobal y la calidad de vida son los deseos principales de los pacientes. Dehecho, la reciente aparición de los llamados Patient Reported Outcomes hasupuesto un importante foco para los agentes involucrados en la asistenciasanitaria. El farmacéutico hospitalario especializado en la evaluación demedicamentos es un profesional que evalúa la eficacia, seguridad, adecuación y eficiencia de los tratamientos prescritos por facultativos, y debebasar la toma de decisiones tanto en factores técnicos como en los cuatroprincipios bioéticos. La correcta aplicación de la práctica clínica basadaen la evidencia permite proveer a los pacientes de incrementos de supervivencia y/o calidad de vida, adecuando la conveniencia y costes a lasituación actual. Teniendo en cuenta esto, podría decirse que la evaluaciónde medicamentos supone un fuerte compromiso con la humanización. Porotra parte, las organizaciones que promueven la evaluación y selecciónde medicamentos rigurosamente se erigen como aliados de los pacientes,ya que repercuten de forma directa en éstos y de forma indirecta en lasociedad. Las agencias reguladoras encargadas de la aprobación y financiación de medicamentos en los sistemas sanitarios protagonizan un papelfundamental en el proceso de humanización de la toma de decisiones clínicas y empoderamiento de pacientes, ya que si aprueban el uso de nuevos medicamentos según datos que no miden la calidad de vida o supervivencia de los pacientes cuando ya existen otras alternativas terapéuticaspara estas patologías, indirectamente no estarán dando respuesta a lasexpectativas de los pacientes y conculcarán los principios bioéticos. (AU)

Patient empowerment is one of the main pillars of humanisation. Therefore,consideration of patients’ preferences and expectations should be takeninto account during the practice of any healthcare professional. Improvingoverall survival and quality of life are the main wishes of patients. Indeed,the recent emergence of Patient Reported Outcomes has become animportant focus for healthcare providers. The hospital pharmacist specialised in drug evaluation is a professional who evaluates the efficacy, safety,appropriateness and efficiency of treatments prescribed by physicians,and decision-making must be based on both technical factors and thefour principles of bioethics. The correct application of evidence-based clinical practice allows to provide patients with increases in survival and/orquality of life, adapting the convenience and costs to the current situation.With this in mind, it could be said that the evaluation of medicines involvesa strong commitment to humanisation. On the other hand, organisationsthat promote the rigorous evaluation and selection of medicines standas allies of patients, as they have a direct impact on them and an indirect impact on society. Regulatory agencies in charge of approving andfinancing medicines in healthcare systems play a key role in the processof humanising clinical decision-making and empowering patients. If theseagencies approve the use of new medicines based on data that do notmeasure quality of life or survival of patients when there are already othertherapeutic alternatives for these pathologies, they are indirectly failing tomeet patients’ expectations and are infringing bioethical principles. (AU)

Clinical characteristics of admission for mental illness in a Regional Psychiatric Hospitalization Unit. Descriptive study 2008-2018 / Características clínicas del ingreso por enfermedad mental en una Unidad de Hospitalización Psiquiátrica Comarcal. Estudio descriptivo 2008-2018.

Objective: To describe the admissions of patients diagnosed with severe mental illness (SMI) and anxiety disorder in a regional hospital; to explore factors related to the patient's referrer upon admission and prolonged stay. Materials and methods: Cross-sectional study of episodes of admission to the regional Psychiatric Hospitalization Unit over a period of 11 years with ICD-10 diagnostic codesF20-29, F30-39, F60-69 and F40-48. The data was extracted through the Admissions Unit and the information from the electronic medical record. For the statistical treatment, descriptive or inferential tests were used with a confidence level of 95%. Results: 961 patients were included (2,324 total discharges), aged 40.8±14.0 years. The most frequent reasons for admission were: positive symptoms (agitation, delusions and hallucinations), followed by suicidal ideation and attempt. The main remitting agent of the patients was the family itself. Approximately 1/5 of the cases were referred by the health system itself, and » of those admitted had self-excluded themselves from specialized supervision for more than a year. Conclusions: The problems that caused the admission and its origin, as well as its lack of follow-up, can be considered as a clear opportunity for improvement in the follow-up of patients with severe mental illness. An orientation towards proactivity, acting before the decompensation, would contribute to improving the care and quality of life of patients with severe mental illness and their environment.

Objetivo: Describir los ingresos de pacientes diagnosticados de enfermedad mental grave y trastorno de ansiedad en un hospital comarcal; explorar los factores relacionados con la derivación del paciente al ingreso y con estancia prolongada. Materiales y métodos: Estudio de corte transversal de los episodios de ingreso en la Unidad de Hospitalización Psiquiátrica comarcal en un periodo de 11 años con los códigos diagnósticos CIE-10 F20-29, F30-39, F60-69 y F40-48. Se extrajeron los datos a través de la Unidad de Admisión y la información de la historia clínica electrónica. Para el tratamiento estadístico se usaron pruebas descriptivas o inferenciales con nivel de confianza del 95%. Resultados: Se incluyeron 961 pacientes (2.324 altas totales), con edad de 40,8±14,0 años. Los motivos más frecuentes de ingreso fueron: síntomas positivos (agitación, delirios y alucinaciones), seguidos de ideación e intento de suicidio. El principal agente remisor de los pacientes fue la propia familia. Aproximadamente 1/5 de casos fue derivado por el propio sistema sanitario, y » de los ingresados se había autoexcluido de la supervisión especializada durante más de un año. Conclusiones: Los problemas causantes del ingreso y su procedencia, así como su falta de seguimiento, pueden considerarse como una oportunidad clara de mejora en el seguimiento del paciente con enfermedad mental grave. Una orientación hacia la proactividad, actuando antes de la descompensación, contribuiría a mejorar la asistencia y calidad de vida de los pacientes con enfermedad mental grave y su entorno.

Manipulación de fármacos para su administración por gastrostomía endoscópica percutánea en pacientes con esclerosis lateral amiotrófica y nutrición enteral / Handling of drugs for administration by percutaneous endoscopic gastrostomy in patients with amyotrophic lateral sclerosis and enteral nutrition

Introducción: la esclerosis lateral amiotrófica (ELA) es una enfermedad neurodegenerativa. Entre sus síntomas destaca la disfagia, que hace necesaria la colocación de una gastrostomía endoscópica percutánea (PEG) para alimentarse. La administración de fármacos por la PEG puede obstruirla, disminuir la eficacia del tratamiento y aumentar el riesgo de toxicidad, al alterar la forma farmacéutica original. Objetivo: describir y analizar el grado de adecuación de la prescripción de fármacos administrados por PEG en pacientes con ELA y con nutrición enteral (NE). Material y métodos: se revisó la prescripción del tratamiento farmacológico de los pacientes con ELA que ingresaban para la colocación de una PEG. Se analizó el grado de adecuación de los fármacos prescritos según los criterios de pérdida de eficacia, toxicidad, riesgo para el manipulador y compatibilidad con la NE, consultando la evidencia científica disponible. Resultados: se revisaron las prescripciones médicas de los tratamientos de 34 pacientes, con un total de 307 medicamentos (mediana de 9 fármacos por paciente; rango, 2-17). Se pautaron por la PEG 267 medicamentos de administración oral (mediana de 8 por paciente; rango, 2-15). El 81,65 % fueron formas sólidas y se modificó la forma farmacéutica en el 43 % por riesgo de oclusión de la sonda, toxicidad o pérdida de eficacia, afectando al 97 % de los pacientes. Conclusiones: los pacientes con ELA y con PEG tienen riesgo de presentar problemas de seguridad y de pérdida de eficacia del tratamiento relacionados con la alteración de la forma farmacéutica original y de la interacción con la NE. Palabras clave: Esclerosis lateral amiotrófica; Gastrostomía endoscópica percutánea; Interacción fármaco-nutriente; Medicamentos peligrosos; Nutrición enteral; Sondas digestivas (AU)

Introduction: amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease. Its symptoms include dysphagia that may make it necessary to place a percutaneous endoscopic gastrostomy (PEG) for feeding. The administration of drugs by PEG can obstruct it, decrease the effectiveness of treatment, and increase the risk of toxicity by altering the original pharmaceutical form. Objective: to describe and analyze the degree of adequacy of the prescription of drugs administered by PEG in patients with ALS and with enteral nutrition (EN). Material and methods: the prescription of pharmacological treatment for patients with ALS who were admitted for placement of a PEG was reviewed. The degree of adequacy of the prescribed drugs was analyzed according to criteria of loss of efficacy, toxicity, risk for handler, and compatibility with EN by consulting the available scientific evidence. Results: the medical prescriptions of the treatments of 34 patients were reviewed, with a total of 307 medications (median of 9 drugs per patient, range 2-17). Via PEG 267 oral medications (median 8 per patient, range 2-15) were prescribed; 81.65 % were solid forms, and the pharmaceutical form was modified in 43 %, due to the risk of catheter occlusion, toxicity or loss of efficacy, affecting 97 % of the patients. Conclusions: patients with ALS and PEG are at risk of presenting safety problems and loss of treatment efficacy related to alteration of the original pharmaceutical form and the interaction with EN (AU)

Heparin versus 0.9% sodium chloride locking for prevention of occlusion in central venous catheters in adults.

BACKGROUND: Intermittent locking of central venous catheters (CVCs) is undertaken to help maintain their patency and performance. There are systematic variations in care: some practitioners use heparin (at different concentrations), whilst others use 0.9% sodium chloride (normal saline). This review looks at the effectiveness and safety of intermittent locking with heparin compared to normal saline, to see if the evidence establishes whether one is better than the other. This is an update of an earlier Cochrane Review. OBJECTIVES: To evaluate the benefits and harms of intermittent locking of CVCs with heparin versus normal saline in adults to prevent occlusion. SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest search date was 20 October 2021. SELECTION CRITERIA: We included randomised controlled trials in adults ≥ 18 years of age with a CVC that compared intermittent locking with heparin at any concentration versus normal saline. We excluded studies on infants and children from this review. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were occlusion of CVCs and duration of catheter patency. Our secondary outcomes were CVC-related bloodstream infections and CVC-related colonisation, mortality, haemorrhage, heparin-induced thrombocytopaenia, CVC-related thrombosis, number of additional CVC insertions, abnormality of coagulation profile and allergic reactions to heparin. We used GRADE to assess the certainty of evidence for each outcome. MAIN RESULTS: We identified one new RCT with 30 participants for this update. We included a total of 12 RCTs with 2422 participants. Data for meta-analysis were available from all RCTs. We noted differences in methods used by the included studies and variation in heparin concentrations (10 to 5000 IU/mL), time to follow-up (1 to 251.8 days), and the unit of analysis used (participant, catheter, line access). Five studies included ICU (intensive care unit) patients, two studies included oncology patients, and the remaining studies included miscellaneous patients (chronic kidney disease, haemodialysis, home care patients, etc.). Primary outcomes Overall, combined results may show fewer occlusions with heparin compared to normal saline but this is uncertain (risk ratio (RR) 0.70, 95% confidence interval (CI) 0.51 to 0.95; 10 studies; 1672 participants; low-certainty evidence). We pooled studies that used participant or catheter as the unit of analysis. We carried out subgroup analysis by unit of analysis. No clear differences were detected after testing for subgroup differences (P = 0.23). We found no clear evidence of a difference in the duration of catheter patency with heparin compared to normal saline (mean difference (MD) 0.44 days, 95% CI -0.10 to 0.99; 6 studies; 1788 participants; low-certainty evidence). Secondary outcomes We found no clear evidence of a difference in the following outcomes: CVC-related bloodstream infections (RR 0.66, 95% CI 0.08 to 5.80; 3 studies; 1127 participants; very low-certainty evidence); mortality (RR 0.76, 95% CI 0.44 to 1.31; 3 studies; 1100 participants; very low-certainty evidence); haemorrhage (RR 1.54, 95% CI 0.41 to 5.74; 3 studies; 1197 participants; very low-certainty evidence); or heparin-induced thrombocytopaenia (RR 0.21, 95% CI 0.01 to 4.27; 3 studies; 443 participants; very low-certainty evidence). The main reasons for downgrading the certainty of evidence for the primary and secondary outcomes were unclear allocation concealment, suspicion of publication bias, imprecision and inconsistency. AUTHORS' CONCLUSIONS: Given the low-certainty evidence, we are uncertain whether intermittent locking with heparin results in fewer central venous catheter occlusions than intermittent locking with normal saline in adults. Low-certainty evidence suggests that heparin may have little or no effect on catheter patency duration. Although we found no evidence of differences in safety (CVC-related bloodstream infections, mortality, or haemorrhage), the combined studies were not powered to detect rare adverse events such as heparin-induced thrombocytopaenia. Further research conducted over longer periods would reduce the current uncertainties.

[Handling of drugs for administration by percutaneous endoscopic gastrostomy in patients with amyotrophic lateral sclerosis and enteral nutrition]. / Manipulación de fármacos para su administración por gastrostomía endoscópica percutánea en pacientes con esclerosis lateral amiotrófica y nutrición enteral.

Introduction: Introduction: amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease. Its symptoms include dysphagia that may make it necessary to place a percutaneous endoscopic gastrostomy (PEG) for feeding. The administration of drugs by PEG can obstruct it, decrease the effectiveness of treatment, and increase the risk of toxicity by altering the original pharmaceutical form. Objective: to describe and analyze the degree of adequacy of the prescription of drugs administered by PEG in patients with ALS and with enteral nutrition (EN). Material and methods: the prescription of pharmacological treatment for patients with ALS who were admitted for placement of a PEG was reviewed. The degree of adequacy of the prescribed drugs was analyzed according to criteria of loss of efficacy, toxicity, risk for handler, and compatibility with EN by consulting the available scientific evidence. Results: the medical prescriptions of the treatments of 34 patients were reviewed, with a total of 307 medications (median of 9 drugs per patient, range 2-17). Via PEG 267 oral medications (median 8 per patient, range 2-15) were prescribed; 81.65 % were solid forms, and the pharmaceutical form was modified in 43 %, due to the risk of catheter occlusion, toxicity or loss of efficacy, affecting 97 % of the patients. Conclusions: patients with ALS and PEG are at risk of presenting safety problems and loss of treatment efficacy related to alteration of the original pharmaceutical form and the interaction with EN.

Introducción: Introducción: la esclerosis lateral amiotrófica (ELA) es una enfermedad neurodegenerativa. Entre sus síntomas destaca la disfagia, que hace necesaria la colocación de una gastrostomía endoscópica percutánea (PEG) para alimentarse. La administración de fármacos por la PEG puede obstruirla, disminuir la eficacia del tratamiento y aumentar el riesgo de toxicidad, al alterar la forma farmacéutica original. Objetivo: describir y analizar el grado de adecuación de la prescripción de fármacos administrados por PEG en pacientes con ELA y con nutrición enteral (NE). Material y métodos: se revisó la prescripción del tratamiento farmacológico de los pacientes con ELA que ingresaban para la colocación de una PEG. Se analizó el grado de adecuación de los fármacos prescritos según los criterios de pérdida de eficacia, toxicidad, riesgo para el manipulador y compatibilidad con la NE, consultando la evidencia científica disponible. Resultados: se revisaron las prescripciones médicas de los tratamientos de 34 pacientes, con un total de 307 medicamentos (mediana de 9 fármacos por paciente; rango, 2-17). Se pautaron por la PEG 267 medicamentos de administración oral (mediana de 8 por paciente; rango, 2-15). El 81,65 % fueron formas sólidas y se modificó la forma farmacéutica en el 43 % por riesgo de oclusión de la sonda, toxicidad o pérdida de eficacia, afectando al 97 % de los pacientes. Conclusiones: los pacientes con ELA y con PEG tienen riesgo de presentar problemas de seguridad y de pérdida de eficacia del tratamiento relacionados con la alteración de la forma farmacéutica original y de la interacción con la NE.

NUTRARET: Effect of 2-Year Nutraceutical Supplementation on Redox Status and Visual Function of Patients With Retinitis Pigmentosa: A Randomized, Double-Blind, Placebo-Controlled Trial.

Oxidative stress plays a major role in the pathogenesis of retinitis pigmentosa (RP). The main goal of this study was to evaluate the effect of 2-year nutritional intervention with antioxidant nutraceuticals on the visual function of RP patients. Secondly, we assessed how nutritional intervention affected ocular and systemic redox status. We carried out a randomized, double-blind, placebo-controlled study. Thirty-one patients with RP participated in the study. RP patients randomly received either a mixture of nutraceuticals (NUT) containing folic acid, vitamin B6, vitamin A, zinc, copper, selenium, lutein, and zeaxanthin or placebo daily for 2 years. At baseline and after 2-year of the nutritional supplementation, visual function, dietetic-nutritional evaluations, serum concentration of nutraceuticals, plasma and aqueous humor concentration of several markers of redox status and inflammation were assessed. Retinal function and structure were assessed by multifocal electroretinogram (mfERG), spectral domain-optical coherence tomography (SD-OCT) and automated visual field (VF) tests. Nutritional status was estimated with validated questionnaires. Total antioxidant capacity, extracellular superoxide dismutase (SOD3), catalase (CAT), and glutathione peroxidase (GPx) activities, protein carbonyl adducts (CAR) content, thiobarbituric acid reactive substances (TBARS) formation (as indicator of lipid peroxidation), metabolites of the nitric oxide (NOX) and cytokine (interleukin 6 and tumor necrosis factor alpha) concentrations were assessed by biochemical and immunological techniques in aqueous humor or/and blood. Bayesian approach was performed to determine the probability of an effect. Region of practical equivalence (ROPE) was used. At baseline, Bayesian analysis revealed a high probability of an altered ocular redox status and to a lesser extent systemic redox status in RP patients compared to controls. Twenty-five patients (10 in the treated arm and 15 in the placebo arm) completed the nutritional intervention. After 2 years of supplementation, patients who received NUT presented better retinal responses (mfERG responses) compared to patients who received placebo. Besides, patients who received NUT showed better ocular antioxidant response (SOD3 activity) and lower oxidative damage (CAR) than those who received placebo. This study suggested that long-term NUT supplementation could slow down visual impairment and ameliorate ocular oxidative stress.

Pharmacotherapeutic management of advanced therapy drugs.

Advanced therapy drugs have emerged in recent years as new pharmacotherapeutic strategies. In this context, hospital pharmacy services have had to adapt to the new challenges posed by the  inclusion of advanced therapies in their roster of services against the  background of the complex pharmacotherapeutic process patients typically go through.All the activities carried out in the hospital pharmacy services must abide by  the rules established in the Spanish legislation and ensure both the quality of  the different drugs they manage and the safety of every single patient.Advanced therapy drugs are associated certain peculiarities, including the need  to select and evaluate potential candidates to receive them; recourse to  financing mechanisms based on risk sharing; and their extreme fragility, which  means that the personnel in charge of handling them must be properly trained  to maintain their viability and that special storage conditions, involving  temperatures below 180 ºC in the case of chimeric antigen receptor T cell  therapies, must be maintained. In addition, use of advanced therapy  medications in the clinical setting has made it necessary for scientific societies  to produce consensus documents recognizing the pivotal role of hospital  pharmacists as indispensable members of the multidisciplinary healthcare team  and ensuring the same traceability, conservation, custody and  pharmacotherapeutical monitoring standards imposed on other drugs to  provide for adequate pharmaceutical care. Scientific societies have also  highlighted the importance of intensifying clinical research, an essential  requirement for the safe incorporation of new therapeutic targets. The present  document is intended to describe the challenges pharmacists may face when  using advanced therapy drugs at the different stages or processes in the  patient's clinical journey.

Los medicamentos de terapia avanzada han emergido en los últimos años  como nuevas estrategias farmacoterapéuticas. En este contexto, los servicios de farmacia hospitalaria nos hemos tenido que adaptar al nuevo reto que ha supuesto su inclusión en nuestra cartera de servicios dentro del  complejo proceso farmacoterapéutico en el que están inmersos los pacientes. Todas las actividades que se desarrollan en los servicios de farmacia hospitalaria cumplen con una base legal establecida en nuestra  legislación y garantizan la calidad y seguridad tanto de los pacientes atendidos  como de todos y cada uno de los medicamentos que se gestionan. Los  medicamentos de terapia avanzada tienen unas características especiales a  considerar que van desde las fases iniciales de selección y evaluación de los  pacientes candidatos y su modelo de financiación, basado en riesgo  compartido, hasta una fragilidad en su manipulación que requiere de una  adecuada y adaptada formación del personal implicado en la logística para  mantener su viabilidad, al necesitar unas condiciones de conservación, en  ocasiones, a temperaturas de menos 180 ºC, en el caso de las células T con  receptores quiméricos de antígenos. Además, la utilización clínica de los  medicamentos de terapia avanzada ha necesitado de documentos de consenso  de las sociedades científicas que pongan en valor el posicionamiento del  farmacéutico hospitalario, como miembro indispensable dentro del equipo  multidisciplinar asistencial, y que garanticen, como en cualquier otro  medicamento, la trazabilidad, la correcta conservación y custodia y el  seguimiento farmacoterapéutico asociado a una adecuada atención  farmacéutica de nuestros pacientes, sin olvidar la importancia de la creciente  investigación clínica, necesaria e imprescindible para una incorporación segura  de nuevas dianas terapéuticas. Por todo ello, consideramos necesario el  presente documento, en donde se ponen de manifiesto los retos o necesidades, desde el punto de vista farmacéutico, en cada una de las etapas o procesos a  considerar en la utilización de los medicamentos de terapia avanzada dentro de nuestro amplio arsenal terapéutico.

Healthcare Resource Utilization among Patients between 60-75 Years with Secondary Acute Myeloid Leukemia Receiving Intensive Chemotherapy Induction: A Spanish Retrospective Observational Study.

BACKGROUND: Information regarding the impact on healthcare systems of secondary acute myeloid leukemia (sAML) is scarce. METHODS: A retrospective review of medical charts identified patients aged 60-75 years with sAML between 2010 and 2019. Patient information was collected from diagnosis to death or last follow-up. Outpatient resource use, reimbursement, frequency and duration of hospitalization, and transfusion burden were assessed. Forty-six patients with a median age of 64 years were included. Anthracycline plus cytarabine regimens were the most common induction treatment (39 patients, 85%). The ratio of the total days hospitalized between the total follow-up was 29%, with a sum of 204 hospitalizations (average four/patient; average duration 21 days). The total average reimbursement was EUR 90,008 per patient, with the majority (EUR 77,827) related to hospital admissions (EUR 17,403/hospitalization). Most hospitalizations (163, mean 22 days) occurred in the period before the first allogeneic hematopoietic stem cell transplant (alloHSCT), costing EUR 59,698 per patient and EUR 15,857 per hospitalization. The period after alloHSCT (in only 10 patients) had 41 hospitalizations (mean 21 days), and a mean reimbursement cost of EUR 99,542 per patient and EUR 24,278 per hospitalization. In conclusion, there is a high consumption of economic and healthcare resources in elderly patients with sAML receiving active treatments in Spain.

Gestión farmacoterapéutica de los medicamentosde terapias avanzadas / Pharmacotherapeutic management of advanced therapy medicinal products

Los medicamentos de terapia avanzada han emergido en los últimosaños como nuevas estrategias farmacoterapéuticas. En este contexto, los serviciosde farmacia hospitalaria nos hemos tenido que adaptar al nuevo retoque ha supuesto su inclusión en nuestra cartera de servicios dentro del complejoproceso farmacoterapéutico en el que están inmersos los pacientes.Todas las actividades que se desarrollan en los servicios de farmaciahospitalaria cumplen con una base legal establecida en nuestra legislacióny garantizan la calidad y seguridad tanto de los pacientes atendidos comode todos y cada uno de los medicamentos que se gestionan.Los medicamentos de terapia avanzada tienen unas característicasespeciales a considerar que van desde las fases iniciales de seleccióny evaluación de los pacientes candidatos y su modelo de financiación,basado en riesgo compartido, hasta una fragilidad en su manipulación querequiere de una adecuada y adaptada formación del personal implicadoen la logística para mantener su viabilidad, al necesitar unas condicionesde conservación, en ocasiones, a temperaturas de menos 180 ºC, en elcaso de las células T con receptores quiméricos de antígenos.Además, la utilización clínica de los medicamentos de terapia avanzadaha necesitado de documentos de consenso de las sociedades científicas utiliquepongan en valor el posicionamiento del farmacéutico hospitalario, comomiembro indispensable dentro del equipo multidisciplinar asistencial, y quegaranticen, como en cualquier otro medicamento, la trazabilidad, la correctaconservación y custodia y el seguimiento farmacoterapéutico asociado auna adecuada atención farmacéutica de nuestros pacientes, sin olvidar laimportancia de la creciente investigación clínica, necesaria e imprescindiblepara una incorporación segura de nuevas dianas terapéuticas.

Advanced therapy medicinal products have emerged in recentyears as new pharmacotherapeutic strategies. In this context, hospitalpharmacy services have had to adapt to the new challenges posed bythe inclusion of advanced therapies in their roster of services againstthe background of the complex pharmacotherapeutic process patientstypically go through.All the activities carried out in the hospital pharmacy services mustabide by the rules established in the Spanish legislation and ensure boththe quality of the different drugs they manage and the safety of every singlepatient.Advanced therapy medicinal products are associated certain peculiarities,including the need to select and evaluate potential candidates toreceive them; recourse to financing mechanisms based on risk sharing; andtheir extreme fragility, which means that the personnel in charge of handlingthem must be properly trained to maintain their viability and that specialstorage conditions, involving temperatures below 180 ºC in the case ofchimeric antigen receptor T cell therapies, must be maintained.In addition, use of advanced therapy medicinal products in the clinicalsetting has made it necessary for scientific societies to produce consensus documents recognizing the pivotal role of hospital pharmacists as indispensablemembers of the multidisciplinary healthcare team and ensuringthe same traceability, conservation, custody and pharmacotherapeuticalmonitoring standards imposed on other drugs to provide for adequate pharmaceuticalcare. Scientific societies have also highlighted the importance ofintensifying clinical research, an essential requirement for the safe incorporationof new therapeutic targets.The present document is intended to describe the challenges pharmacistsmay face when using advanced therapy medicinal products at thedifferent stages or processes in the patient’s clinical journey.

A systematic review and meta-analysis of the effectiveness and adverse events of gabapentin and pregabalin for sciatica pain / Revisión sistemática y metaanálisis sobre la efectividad y eventos adversos de gabapentina y pregabalina para el dolor de ciática

Aim: This SR aims to assess the effectiveness of pregabalin and gabapentin on pain and disability caused by acute sciatica and the adverse events associated with their clinical use.DesignSystematic review.DatabasesElectronic databases of Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, and Clinical Trials.gov were searched from their inception until March 1st of 2021.Selection criteriaRandomized trials (RCT) with adults>18 years old with acute sciatica for a minimum of 1 week and a maximum of 1 year (at least moderate pain).Data treatmentThe outcomes were pain, disability and adverse events. Data was summarized using odds ratio and mean difference. GRADE was used to calculate the level of evidence.ResultsEight RCT involving 747 participants were included. The effect of pregabalin was assessed in 3 RCT and in one three-arm trial (pregabalin vs limaprost vs a combination of limaprost and pregabalin). Two trials assessed the effect of gabapentin compared with placebo and one compared with tramadol. One study assessed the effect of gabapentin vs pregabalin in a crossover head-to-head trial.A statistically significant improvement on leg pain at 2 weeks and leg pain with movement at 3 and 4 months was found in a RCT comparing gabapentin with placebo. There were no statistically differences on the remaining time periods assessed for leg pain, low back pain and functional disability.ConclusionsThis SR provides clear evidence for lack of effectiveness of pregabalin and gabapentin for sciatica pain management. In view of this, its routine clinical use cannot be supported.

Objetivo: Esta revisión sistemática evalúa la efectividad de pregabalina y gabapentina sobre el dolor y la discapacidad producidas por el dolor agudo causado por ciática, y los eventos adversos asociados al uso clínico.DiseñoRevisión sistemática.Bases de datosSe buscó en Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, y en Clinical Trials.gov desde su inicio hasta el 1 de marzo del 2021.Criterios de selecciónEnsayos clínicos aleatorizados (ECA) sobre adultos > 18 años con ciática aguda establecida entre una semana como mínimo y un año como máximo (al menos con dolor moderado).Tratamiento de datosLos resultados fueron dolor, discapacidad y eventos adversos. Los datos fueron resumidos usando odds ratio y diferencia de medias. Para calcular el nivel de evidencia se empleó GRADE.ResultadosSe incluyeron 8 ECA con un total de 747 participantes. El efecto de la pregabalina fue evaluado en 3 ECA y en un ensayo de 3 brazos (pregabalina vs. limaprost vs. una combinación de limaprost y pregabalina). Dos ensayos evaluaron el efecto de gabapentina comparado con placebo y uno lo comparó con tramadol. Un estudio evaluó el efecto de gabapentina vs. pregabalina en un ensayo cruzado.En un ECA se encontró una diferencia estadísticamente significativa en la mejora del dolor de piernas a las 2 semanas y en el dolor de piernas con el movimiento a los 3 y 4 meses, con gabapentina comparado frente a placebo. No hubo diferencias en el resto de los periodos estudiados para el dolor de piernas, dolor en la zona lumbar o en la discapacidad funcional.ConclusionesEsta revisión sistemática ofrece evidencia clara de la falta de pruebas sobre la efectividad de pregabalina o gabapentina para el manejo del dolor derivado de la ciática. Por tanto, su uso clínico rutinario no está avalado.

Baricitinib against severe COVID-19: effectiveness and safety in hospitalised pretreated patients.

OBJECTIVES: To analyse the effectiveness and safety of baricitinib for severe COVID-19 in cytokine storm syndrome based on its potential role as an anti-inflammatory immunomodulator and inhibitor of viral endocytosis. METHODS: This was an observational retrospective study of hospitalised patients treated with baricitinib for severe COVID-19. Outcomes were clinical improvement on an ordinal scale of 1-8 on day 1 of baricitinib compared with day 14 (where 8=death and 1=not hospitalised with no limitations of activities), overall survival, time to recovery since baricitinib treatment started (days until hospital discharge) and laboratory parameters related to COVID-19 poor prognosis. Adverse events related to baricitinib during the admission period were also reported. RESULTS: Forty-three patients (70% men, mean age 70 years (IQR 54-79)) treated with baricitinib daily for 6 days (IQR 5-7) were included. Thirty-six patients were treated with corticosteroids (84%). Clinical improvement was 3 points (IQR 1-4) in patients on an ordinal scale of 4-6, overall survival was 100% at day 30 and day 60 with a mean time to recovery of 12 days (IQR 9-25) from start of baricitinib treatment. No adverse events of interest were found and all poor prognosis risk factors improved at day 14: interleukin-6, C-reactive protein, ferritin, lymphocytes, platelets and D-dimers. CONCLUSIONS: Patients treated with baricitinib for severe COVID-19 showed improvements in clinical and analytical values without relevant adverse events and 100% overall survival. Clinical randomised trials are needed to confirm the clinical benefit of baricitinib.

A systematic review and meta-analysis of the effectiveness and adverse events of gabapentin and pregabalin for sciatica pain.

AIM: This SR aims to assess the effectiveness of pregabalin and gabapentin on pain and disability caused by acute sciatica and the adverse events associated with their clinical use. DESIGN: Systematic review. DATABASES: Electronic databases of Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, and Clinical Trials.gov were searched from their inception until March 1st of 2021. SELECTION CRITERIA: Randomized trials (RCT) with adults>18 years old with acute sciatica for a minimum of 1 week and a maximum of 1 year (at least moderate pain). DATA TREATMENT: The outcomes were pain, disability and adverse events. Data was summarized using odds ratio and mean difference. GRADE was used to calculate the level of evidence. RESULTS: Eight RCT involving 747 participants were included. The effect of pregabalin was assessed in 3 RCT and in one three-arm trial (pregabalin vs limaprost vs a combination of limaprost and pregabalin). Two trials assessed the effect of gabapentin compared with placebo and one compared with tramadol. One study assessed the effect of gabapentin vs pregabalin in a crossover head-to-head trial. A statistically significant improvement on leg pain at 2 weeks and leg pain with movement at 3 and 4 months was found in a RCT comparing gabapentin with placebo. There were no statistically differences on the remaining time periods assessed for leg pain, low back pain and functional disability. CONCLUSIONS: This SR provides clear evidence for lack of effectiveness of pregabalin and gabapentin for sciatica pain management. In view of this, its routine clinical use cannot be supported.

Analysis of chemical contamination by hazardous drugs with BD HD Check® system in a tertiary hospital.

The presence of contamination in the healthcare work environment by one of the types of hazardous drugs, cytostatics, has been found in multiple international studies. Recent studies and guidelines recommend surface monitoring for risk assessment of healthcare professionals' exposure. The availability of detection techniques is critical to successfully carry out this type of monitoring. The use of new semi-quantitative techniques allows quicker results. The main objective of this study was to determine the existence of hazardous drugs on the working surfaces in different locations of a tertiary hospital using the BD HD Check® semi-quantitative device. The presence of methotrexate, doxorubicin and cyclophosphamide was analysed at 80, 89 and 82 locations in 10, 13 and 11 clinical units, respectively. A total of 251 samples were analysed. The monitoring results were positive for 13.1% of the analysed samples, with 36.3% of the methotrexate samples, 0% of the doxorubicin samples and 4.9% of the cyclophosphamide samples. Mapping the presence of HD in our hospital has allowed us to evaluate the effectiveness of controls established in the hospital to minimise the exposure of healthcare professionals to hazardous drugs. The speed in obtaining results has enabled immediate corrective actions in cases where contaminated surfaces were detected.

Evaluar medicamentos también es una actividad clínica / Drug evaluation is also a clinical activity

La especialidad de Farmacia Hospitalaria incorporó con el cuarto año de su programa formativo una parte importante de rotación por unidades clínicas de hospitalización en las que el farmacéutico en formación, acompañado de farmacéuticos especialistas, tiene la oportunidad de trabajar conjuntamente con otros profesionales en la atención directa al paciente. Además de contribuir a esta atención con sus conocimientos de farmacoterapia y farmacocinética, el farmacéutico de hospital puede y debe aportar al equipo su liderazgo en evaluación, selección y posicionamiento de medicamentos. Ningún profesional conoce como él los aspectos relativos a la eficacia o efectividad, seguridad y eficiencia de los tratamientos, y estos conocimientos constituyen una actividad clínica más de las que debe desempeñar en los equipos multidisciplinares, ayudando a la toma de decisiones sobre medicamentos en cada paciente. Es necesario que tanto desde los organismos públicos como desde nuestra propia profesión se ponga en valor este papel y que se potencie de forma adecuada

The addition of a fourth year to the hospital pharmacy residency program has allowed trainees to rotate through various inpatient clinical units where they can, under the supervision of a specialist pharmacist, work shoulder to shoulder with other healthcare providers to ensure that patients receive the care they need. In addition to sharing their pharmacotherapeutic and pharmacokinetic knowledge (among others) with their colleagues, hospital pharmacists can and should contribute with their expertise in the areas of drug evaluation, selection and positioning. As no other healthcare professional masters like a pharmacist the intricacies of treatment efficacy or effectiveness, or of therapeutic safety, conveying this knowledge is yet another of the many clinical activities a hospital pharmacist must perform as a member of a multidisciplinary team, while assisting fellow-team members in deciding what medications are best suited to each patient. Both the public authorities and the pharmaceutical profession as a whole should make sure the pharmacist's role is rightfully valued and given the recognition it deserves

Involvement of interleukin 6 in SARS-CoV-2 infection: siltuximab as a therapeutic option against COVID-19.

The aim of the study was to explore the involvement of interleukin 6 in SARS-CoV-2 infection, and to position the drug siltuximab in the management of severe forms of COVID-19. A bibliographic search was performed in Pubmed on the immune response to the disease, and in ClinicalTrials.gov on clinical trials with interleukin 6 blockers. Interleukin 6 is involved in the cytokine cascade, which originates as a consequence of an excessive immune response secondary to viral infection, aggravating lung affectation. Blockers of this cytokine (tocilizumab, sarilumab and siltuximab) are being studied as a strategy for treating the disease. Siltuximab is a monoclonal antibody indicated in Castleman's disease that could be administered in a single dose of 11 mg/kg in severe forms of COVID-19 that have increased interleukin 6.