Systematic review and meta-analysis of interleulin-6 inhibitors in reducing mortality for hospitalized patients with COVID-19.

OBJECTIVE: One year after the declaration of the SARS-CoV-2 pandemic, only  dexamethasone has clearly shown a reduction in mortality for COVID-19  hospitalized patients. For interleukin-6 inhibitors, results are variable and  nclear. The objective was to review and analyze the effect of tocilizumab and  sarilumab on survival in this setting. METHOD: The PRISMA statements were fulfilled for the systematic review. A  systematic search in Medline, Embase and medRxiv was conducted to identify  randomized controlled trials with tocilizumab or sarilumab in hospitalized  patients with COVID-19. Mortality data from non-critical and critical patients  were extracted. A random-effects (DerSimonian-Laird) meta-analysis was  performed for both subgroups and the whole population using MAVIS software  v. 1.1.3. Similarity and homogeneity among trials were assessed. RESULTS: Twenty-five and 23 articles were identified in Medline and Embase,  respectively, five were trials with tocilizumab and/or sarilumab; two more were  identified at medRxiv. Seven randomized clinical trials fulfilled the  inclusion criteria. Another trial was pre-published and included post-hoc. The  meta-analysis, with eight randomized clinical trials and 6,340 patients, showed  a benefit on mortality for interleukin-6  heterogeneity (I2 = 7%), but  a low similarity among studies. The results showed no differences among  critical and non-critical patients. A sensitivity analysis excluding non-similar or  heterogeneous studies showed different results, without benefit and with low  precision of the result in non-critical patients. CONCLUSIONS: A benefit in mortality for interleukine-6 inhibitors was found, but  with important differences among the scenarios analyzed in the clinical  trials. Positive results are mainly caused by two randomized clinical trials which  are similar in concomitant use of steroids and veryhigh mortality in  critical patents. Sarilumab was poorly represented in the meta-analysis.  Nevertheless, an association between the benefit and the critical/non-critical  condition was not found. More randomized clinical trials, mainly focused in  atients at high mortality risk, are needed to confirm the benefit of interleukine- 6 inhibitors for COVID-19. Sarilumab was underrepresented in the meta- analysis.

OBJETIVO: Un año después de la declaración de la pandemia por SARS­CoV-2,  solo dexametasona había mostrado claramente una reducción de la mortalidad  en pacientes hospitalizados por COVID-19. Los resultados de los inhibidores de  interleucina 6 son diversos y poco claros. El objetivo de este trabajo es  revisar y analizar el efecto de tocilizumab y sarilumab sobre la supervivencia  de los pacientes en este escenario.Método: La revisión sistemática siguió las recomendaciones de PRISMA. Se  realizó una búsqueda sistemática en Medline, Embase y medRxiv para identificar ensayos controlados aleatorizados con tocilizumab o sarilumab  en pacientes hospitalizados con COVID-19. Se recopilaron los datos de mortalidad de pacientes críticos y no críticos y se llevó a cabo un metaanálisis de efectos aleatorios (Der Simonian-Laird) para ambos  subgrupos y para toda la población, usando el software MAVIS v. 1.1.3. La similitud y homogeneidad entre los ensayos fue evaluada. RESULTADOS: Se identificaron 25 y 23 artículos en Medline y Embase, respectivamente; cinco eran ensayos con tocilizumab y/o sarilumab;  se identificaron dos más en medRxiv. En total, siete ensayos clínicos  aleatorizados cumplieron los criterios de inclusión. Posteriormente, se  prepublicó otro ensayo que cumplía los criterios de inclusión y se incorporó al  análisis. El metaanálisis, con ocho ensayos clínicos aleatorizados y 6.340  pacientes, mostró un beneficio sobre la mortalidad para los inhibidores de  interleucina-6 (hazard ratio 0,85; intervalo de confianza al 95% 0,74-0,99),  con baja heterogeneidad (I2 = 7%), pero reducida similitud entre los estudios.  Los resultados no mostraron diferencias entre pacientes críticos y no  críticos. Un análisis de sensibilidad excluyendo estudios heterogéneos o no  similares mostró resultados diferentes, sin beneficio y con baja precisión del  resultado en pacientes no críticos. CONCLUSIONES: Se encontró un beneficio en la mortalidad de los inhibidores de  la interleucina 6, pero con importantes diferencias entre los escenarios analizados en los ensayos clínicos. Los resultados positivos se  eben principalmente a dos ensayos que son similares en el uso concomitante  de esteroides y una mortalidad muy alta en pacientes críticos. Sarilumab estuvo escasamente representado en el metaanálisis. Sin embargo, el metaanálisis por subescenarios no encontró una relación entre  el beneficio y la condición de pacientes críticos/no críticos. Se necesitan más ensayos clínicos aleatorizados, principalmente enfocados en  pacientes con alto riesgo de mortalidad, para confirmar el beneficio de los  inhibidores de interleucina-6 en COVID-19.

Machine-learning-derived predictive score for early estimation of COVID-19 mortality risk in hospitalized patients.

The clinical course of COVID-19 is highly variable. It is therefore essential to predict as early and accurately as possible the severity level of the disease in a COVID-19 patient who is admitted to the hospital. This means identifying the contributing factors of mortality and developing an easy-to-use score that could enable a fast assessment of the mortality risk using only information recorded at the hospitalization. A large database of adult patients with a confirmed diagnosis of COVID-19 (n = 15,628; with 2,846 deceased) admitted to Spanish hospitals between December 2019 and July 2020 was analyzed. By means of multiple machine learning algorithms, we developed models that could accurately predict their mortality. We used the information about classifiers' performance metrics and about importance and coherence among the predictors to define a mortality score that can be easily calculated using a minimal number of mortality predictors and yielded accurate estimates of the patient severity status. The optimal predictive model encompassed five predictors (age, oxygen saturation, platelets, lactate dehydrogenase, and creatinine) and yielded a satisfactory classification of survived and deceased patients (area under the curve: 0.8454 with validation set). These five predictors were additionally used to define a mortality score for COVID-19 patients at their hospitalization. This score is not only easy to calculate but also to interpret since it ranges from zero to eight, along with a linear increase in the mortality risk from 0% to 80%. A simple risk score based on five commonly available clinical variables of adult COVID-19 patients admitted to hospital is able to accurately discriminate their mortality probability, and its interpretation is straightforward and useful.

Revisión sistemática y metaanálisis de inhibidores de interleucina-6 para reducir la mortalidad en pacientes hospitalizados con COVID-19 / Systematic review and meta-analysis of interleulin-6 inhibitors in reducing mortality for hospitalized patients with COVID-19

Objetivo: Un año después de la declaración de la pandemia porSARS‑CoV-2, solo dexametasona había mostrado claramente una reducciónde la mortalidad en pacientes hospitalizados por COVID-19. Losresultados de los inhibidores de interleucina 6 son diversos y poco claros.El objetivo de este trabajo es revisar y analizar el efecto de tocilizumaby sarilumab sobre la supervivencia de los pacientes en este escenario.Método: La revisión sistemática siguió las recomendaciones de PRISMA.Se realizó una búsqueda sistemática en Medline, Embase y medRxiv paraidentificar ensayos controlados aleatorizados con tocilizumab o sarilumaben pacientes hospitalizados con COVID-19. Se recopilaron los datosde mortalidad de pacientes críticos y no críticos y se llevó a cabo unmetaanálisis de efectos aleatorios (Der Simonian-Laird) para ambos subgruposy para toda la población, usando el software MAVIS v. 1.1.3. Lasimilitud y homogeneidad entre los ensayos fue evaluada.Resultados: Se identificaron 25 y 23 artículos en Medline y Embase,respectivamente; cinco eran ensayos con tocilizumab y/o sarilumab; seidentificaron dos más en medRxiv. En total, siete ensayos clínicos aleatorizadoscumplieron los criterios de inclusión. Posteriormente, se prepublicóotro ensayo que cumplía los criterios de inclusión y se incorporó absoalanálisis. El metaanálisis, con ocho ensayos clínicos aleatorizados y6.340 pacientes, mostró un beneficio sobre la mortalidad para los inhibidoresde interleucina-6 (hazard ratio 0,85; intervalo de confianza al 95%0,74-0,99), con baja heterogeneidad (I2 = 7%), pero reducida similitudentre los estudios. Los resultados no mostraron diferencias entre pacientescríticos y no críticos. Un análisis de sensibilidad excluyendo estudios heterogéneoso no similares mostró resultados diferentes, sin beneficio y conbaja precisión del resultado en pacientes no críticos.

Objective: One year after the declaration of the SARS-CoV-2 pandemic,only dexamethasone has clearly shown a reduction in mortality forCOVID-19 hospitalized patients. For interleukin-6 inhibitors, results arevariable and unclear. The objective was to review and analyze the effectof tocilizumab and sarilumab on survival in this setting.Method: The PRISMA statements were fulfilled for the systematic review.A systematic search in Medline, Embase and medRxiv was conductedto identify randomized controlled trials with tocilizumab or sarilumab inhospitalized patients with COVID-19. Mortality data from non-critical andcritical patients were extracted. A random-effects (DerSimonian-Laird)meta-analysis was performed for both subgroups and the whole populationusing MAVIS software v. 1.1.3. Similarity and homogeneity amongtrials were assessed.Results: Twenty-five and 23 articles were identified in Medline andEmbase, respectively, five were trials with tocilizumab and/or sarilumab;two more were identified at medRxiv. Seven randomized clinical trialsfulfilled the inclusion criteria. Another trial was pre-published and includedpost-hoc. The meta-analysis, with eight randomized clinical trialsand 6,340 patients, showed a benefit on mortality for interleukin-6 inhibitor (hazard ratio 0.85; confidence interval 95% 0.74-0.99), lowheterogeneity (I2 = 7%), but a low similarity among studies. The resultsshowed no differences among critical and non-critical patients. A sensitivityanalysis excluding non-similar or heterogeneous studies showeddifferent results, without benefit and with low precision of the result innon-critical patients.

Coste-efectividad e impacto presupuestario del tratamiento con evolocumab frente a estatinas y ezetimiba para la hipercolesterolemia en España / Cost-effectiveness and budget impact of treatment with evolocumab versus statins and ezetimibe for hypercholesterolemia in Spain

Introducción y objetivos: Analizar la razón de coste-efectividad y el impacto presupuestario del tratamiento con evolocumab (inhibidor de la PCSK9) para pacientes en prevención secundaria en el Sistema Nacional de Salud español. Métodos: Se realizaron, desde la perspectiva del sistema sanitario público, análisis de impacto presupuestario, modelos de árbol de decisión y Markov, basándose en el único ensayo clínico con datos de morbimortalidad (FOURIER). Las alternativas comparadas fueron evolocumab frente a estatinas y un 5% ezetimiba conjuntamente. La medida de eficacia utilizada fue el número de eventos cardiovasculares evitados. Se realizaron análisis de sensibilidad univariable y probabilístico. Resultados: El coste sanitario promedio de los pacientes tratados a 26 meses con evolocumab fue de 11.134,78 euros y de 393,83 euros con el estándar (estatinas + ezetimiba). El coste-efectividad incremental superó los 600.000 euros por evento cardiovascular evitado en las 2 variables (primera: muerte cardiovascular, infarto de miocardio, accidente cerebrovascular, hospitalización por angina inestable o revascularización coronaria; segunda: incluye los 3 primeros eventos). A 10 años, el modelo de Markov mostró un coste promedio de 471.417,37 frente a 13.948,45 euros con evolocumab y estándar respectivamente. El tratamiento con evolocumab en hipercolesterolemia familiar supondría anualmente entre 3 y 6,1 millones de euros, lo que supone una diferencia de 2,5-5,1 millones de euros con el tratamiento estándar (2017). Para el año 2021, en hipercolesterolemia no familiar (prevención secundaria), la diferencia osciló entre 204,3 y 1.364,7 millones de euros. Conclusiones: El evolocumab se asocia con menor frecuencia de eventos cardiovasculares, pero resulta ineficiente para los pacientes susceptibles de recibirlo en el Sistema Nacional de Salud

Introduction and objectives: To analyze the cost-effectiveness ratio and budget impact of treatment with evolocumab (PCSK9 inhibitor) for patients in secondary prevention in the Spanish National Health System. Methods: A budget impact analysis, decision tree and Markov models were designed under the public health system perspective, based on the only study with morbidity and mortality data (FOURIER). The alternatives compared were evolocumab vs statins, and dual therapy with ezetimibe in 5% of the population. The measure of effectiveness used was the number of cardiovascular events avoided. Univariate and probabilistic sensitivity analyses were performed. Results: The average annual cost of patients receiving evolocumab was 11 134.78€ and 393.83€ for standard treatment (statins plus ezetimibe). The incremental cost-effectiveness ratio was > 600 000 € per avoided cardiovascular event for both assessed outcomes (first: cardiovascular death, myocardial infarction, stroke, and hospitalization due to unstable angina or coronary revascularization; second: includes the first 3 events). To perform the 10-year Markov model, the average cost of standard treatment was 13 948.45€ vs 471 417.37€ with evolocumab. Treatment with evolocumab for patients with familial hypercholesterolemia would cost between 3 and 6.1 million euros, assuming a difference of 2.5 and 5.1 million euros with the standard treatment (2017). This difference would be between 204.3 and 1364.7 million euros (2021) for those with nonfamiliar hypercholesterolemia (secondary prevention). Conclusions: Treatment with evolocumab is associated with a lower frequency of cardiovascular events, but is inefficient for patients suitable to receive this drug in the Spanish National Health System

Cost-effectiveness and Budget Impact of Treatment with Evolocumab Versus Statins and Ezetimibe for Hypercholesterolemia in Spain.

INTRODUCTION AND OBJECTIVES: To analyze the cost-effectiveness ratio and budget impact of treatment with evolocumab (PCSK9 inhibitor) for patients in secondary prevention in the Spanish National Health System. METHODS: A budget impact analysis, decision tree and Markov models were designed under the public health system perspective, based on the only study with morbidity and mortality data (FOURIER). The alternatives compared were evolocumab vs statins, and dual therapy with ezetimibe in 5% of the population. The measure of effectiveness used was the number of cardiovascular events avoided. Univariate and probabilistic sensitivity analyses were performed. RESULTS: The average annual cost of patients receiving evolocumab was 11 134.78€ and 393.83€ for standard treatment (statins plus ezetimibe). The incremental cost-effectiveness ratio was > 600 000 € per avoided cardiovascular event for both assessed outcomes (first: cardiovascular death, myocardial infarction, stroke, and hospitalization due to unstable angina or coronary revascularization; second: includes the first 3 events). To perform the 10-year Markov model, the average cost of standard treatment was 13 948.45€ vs 471 417.37€ with evolocumab. Treatment with evolocumab for patients with familial hypercholesterolemia would cost between 3 and 6.1 million euros, assuming a difference of 2.5 and 5.1 million euros with the standard treatment (2017). This difference would be between 204.3 and 1364.7 million euros (2021) for those with nonfamiliar hypercholesterolemia (secondary prevention). CONCLUSIONS: Treatment with evolocumab is associated with a lower frequency of cardiovascular events, but is inefficient for patients suitable to receive this drug in the Spanish National Health System.

Revisión crítica de la oritavancina en infecciones de la piel y tejidos blandos / Review of oritavancin for the treatment of acute bacterial skin and skin structure infections

Objetivo: Evaluar críticamente la oritavancina, lipoglicopéptido de segunda generación, para el tratamiento de la infección bacteriana aguda de la piel y tejidos blandos causada por bacterias Gram-positivas susceptibles, incluyendo Staphylococcus aureus resistente a meticilina. Método: Se realizó un informe de evaluación según la metodología del Grupo de Evaluación de Novedades, Estandarización e Investigación en Selección de Medicamentos de la Sociedad Española de Farmacia Hospitalaria, con el programa MADRE 4.0. Se llevó a cabo una búsqueda en PubMed, en www.clinicaltrials.gov, Embase y UptoDate. También se utilizaron informes publicados de agencias de evaluación. Resultados: La oritavancina en dosis única demostró no ser inferior a la vancomicina en Infección bacteriana aguda de la piel y tejidos blandos, con un perfil de seguridad similar. Sus ventajas potenciales frente a otras alternativas terapéuticas radicarían en su administración en dosis única y en la no necesidad de monitorización de los niveles plasmáticos (lo que posibilitaría su administración ambulatoria), y en la mejora de la adherencia. Aunque podría ser eficiente en determinados escenarios (tratamiento ambulatorio frente al hospitalario con las alternativas), no hay estudios convincentes en este sentido. Por otra parte, los fármacos alternativos por vía oral (linezolid, tedizolid) o IM (teicoplanina) pueden permitir también el tratamiento ambulatorio, reduciendo las ventajas de la oritavancina y agrandando las diferencias de coste. Dado que su eficacia es similar a las alternativas, cabría considerar un análisis de minimización de costes. Conclusiones: La oritavancina es de una eficacia y seguridad comparables a las alternativas existentes en Infección bacteriana aguda de la piel y tejidos blandos y no mejora la relación coste-efectividad, por lo que el posicionamiento propuesto sería el tratamiento de la infección por enterococo resistente a vancomicina en pacientes adultos cuando esté contraindicado el uso de linezolid o tedizolid (AU)

Objective: To assess critically oritavancin, a second-generation lipoglycopeptide, for the treatment of Acute Bacterial Skin and Skin Structure Infections caused by susceptible Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus. Method: An evaluation report of oritavancin in Acute Bacterial Skin and Skin Structure Infections was carried out according to the methodology of the Group for drug evaluation, standardization and research in drug selection of the Spanish Society of Hospital Pharmacy (SEFH)1 , with the MADRE 4.0 program. A search was made in PubMed, in the web www.clinicaltrials. gov, Embase, PubMed and UptoDate. The European Medication Agency and Food and Drug Administration evaluation reports were also used. Results: Single-dose oritavancin demonstrated its non-inferiority efficacy versus vancomycin in Acute Bacterial Skin and Skin Structure Infections, with a similar safety profile. Its potential advantage over other therapeutic alternatives lies in its administration in single dose and in its no need for plasma levels monitoring, which would allow its administration on an outpatient basis. Regarding to the other alternative possibilities of oral (linezolid, tedizolid) or IM (teicoplanin) treatment, oritavancin would improve the adherence to the treatment. Although oritavancin could be more efficient in certain scenarios (outpatient treatment versus inpatient treatment with alternatives), there are no convincing studies in this regard so far. On the other hand, alternative drugs above-mentioned, can also allow outpatient treatment, reducing advantages of oritavancin and further increasing cost differences. Therefore, given that the efficacy is similar to the alternatives, a cost minimization analysis could be considered. Conclusions: Oritavancin is comparable in terms of efficacy and safety to the existing alternatives in Acute Bacterial Skin and Skin Structure Infections, without improvements in the cost-effectiveness ratio, because of the proposed positioning is to consider it for the treatment of vancomycin resistant enterococcal infection in adult patients when the use of linezolid or tedizolid is contraindicated (AU)

Review of oritavancin for the treatment of acute bacterial skin and skin structure infections.

OBJECTIVE: To assess critically oritavancin, a second-generation  lipoglycopeptide, for the treatment of Acute Bacterial Skin and Skin Structure Infections caused by susceptible Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus. METHOD: An evaluation report of oritavancin in Acute Bacterial Skin and Skin  Structure Infections was carried out according to the methodology of the Group  for drug evaluation, standardization and research in drug selection of the  Spanish Society of Hospital Pharmacy (SEFH)1, with the MADRE 4.0 program. A  search was made in PubMed, in the web www.clinicaltrials. gov, Embase,  PubMed and UptoDate. The European Medication Agency and Food and Drug  Administration evaluation reports were also used. RESULTS: Single-dose oritavancin demonstrated its non-inferiority efficacy versus  vancomycin in Acute Bacterial Skin and Skin Structure  nfections, with a similar safety profile. Its potential advantage over other  therapeutic alternatives lies in its administration in single dose and in its no need for plasma levels monitoring, which would allow its administration on an outpatient basis. Regarding to the other alternative possibilities of oral  (linezolid, tedizolid) or IM (teicoplanin) treatment, oritavancin would improve the  adherence to the treatment. Although oritavancin could be more  efficient in certain scenarios (outpatient treatment versus inpatient treatment  with alternatives), there are no convincing studies in this regard so far. On the  other hand, alternative drugs above-mentioned, can also allow outpatient  treatment, reducing advantages of oritavancin and further increasing cost  differences. Therefore, given that the efficacy is similar to the alternatives, a  cost minimization analysis could be considered. CONCLUSIONS: Oritavancin is comparable in terms of efficacy and safety to the  existing alternatives in Acute Bacterial Skin and Skin Structure Infections,  without improvements in the cost-effectiveness ratio, because of the proposed  positioning is to consider it for the treatment of  vancomycinresistant enterococcal infection in adult patients when the use of  linezolid or tedizolid is contraindicated.

Objetivo: Evaluar críticamente la oritavancina, lipoglicopéptido de segunda generación, para el tratamiento de la infección bacteriana aguda de la  piel y tejidos blandos causada por bacterias Gram-positivas susceptibles,  incluyendo Staphylococcus aureus resistente a meticilina.Método: Se realizó un informe de evaluación según la metodología del Grupo de Evaluación de Novedades, Estandarización e Investigación en Selección de  Medicamentos de la Sociedad Española de Farmacia Hospitalaria, con el  programa MADRE 4.0. Se llevó a cabo una búsqueda en PubMed, en  www.clinicaltrials.gov, Embase y UptoDate. También se utilizaron informes  publicados de agencias de evaluación.Resultados: La oritavancina en dosis única demostró no ser inferior a la vancomicina en Infección bacteriana aguda de la piel y tejidos blandos, con un perfil de seguridad similar. Sus ventajas potenciales frente a otras alternativas  terapéuticas radicarían en su administración en dosis única y en la no necesidad  de monitorización de los niveles plasmáticos (lo que posibilitaría su  administración ambulatoria), y en la mejora de la adherencia. Aunque podría ser  eficiente en determinados escenarios (tratamiento ambulatorio frente al  hospitalario con las alternativas), no hay estudios convincentes en este sentido.  Por otra parte, los fármacos alternativos por vía oral (linezolid, tedizolid) o IM  (teicoplanina) pueden permitir también el tratamiento ambulatorio, reduciendo  las ventajas de la oritavancina y agrandando las diferencias de coste. Dado que  su eficacia es similar a las alternativas, cabría considerar un análisis de  minimización de costes.Conclusiones: La oritavancina es de una eficacia y seguridad comparables a las alternativas existentes en Infección bacteriana aguda de la piel y tejidos blandos y no mejora la relación coste-efectividad, por lo que el posicionamiento  propuesto sería el tratamiento de la infección por enterococo resistente a  vancomicina en pacientes adultos cuando esté contraindicado el uso de linezolid  o tedizolid.

Degree of prescriber's knowledge about variability in biological drugs "innovators" in manufacturing process.

PURPOSE: The purpose of the study is to analyse the degree of prescribers' knowledge about the regulation and variability in manufacturing processes (MP) in bio-drugs "innovators" (BI). METHODS: For each selected drugs, the date of authorization by the European Medicines Agency, time elapsed until the first change, total number of changes and annual rate of change (ARC) were recorded. A survey was designed with 4 parts: (a) identifying the BI prescribed; (b) knowledge of the number and ARC of each BI during its MP; (c) knowledge of comparability requirement of BI before or after the MP; (d) evaluating the utility of the information in the survey. RESULTS: Drugs selected and total number of changes: infliximab (41), adalimumab (20), abatacept (13), golimumab (7), etanercept (18), tocilizumab (6) and certolizumab. All BI had been changed in the MP after their authorisation. The survey was answered by 35 professionals from rheumatology, digestive and dermatology area. They had prescribed one or more drugs included in the survey at least once. Sixty-three percent of prescribers did not know the existence of changes relative to the MP. Thirty-seven percent of prescribers knew of their existence, but not about number or frequency. Fifty-seven percent of prescribers did not know the regulation about the comparability among BI. The rest of them knew it, but 29% related it only to biosimilar drugs. Ninety-four percent of prescribers identified information as useful. CONCLUSION: BI present a high ARC during their MP after their commercialization, without any efficacy or safety difficulties. Knowledge of this might increase confidence for biosimilars.

A randomised controlled trial on the efficacy of a multidisciplinary health care team on morbidity and mortality of elderly patients attending the Emergency Department. Study design and preliminary results / Ensayo clínico aleatorizado sobre la eficacia de un equipo multidisciplinar en la morbimortalidad de pacientes ancianos atendidos en un servicio de urgencias. Diseño y resultados preliminares

Objective: To estimate the prevalence of potentially inadequate drug prescriptions in elderly patients who attend the Emergency Department. Design: A multicentre randomized clinical trial. Patients over 65 years of age attending the Emergency Department are randomized to the control arm or the intervention arm. In the intervention arm, the pharmacist will review the chronic medication of patients and identify any potentially inadequate prescriptions, according to the STOPP-START criteria. The cases are discussed with the Emergency Specialist and, if considered adequate, a recommendation to modify the treatment is sent to the Primary Care Physician. The control arm will receive the standard of care, not including a systematic review of the adequacy to the STOPP-START criteria. This article presents preliminary outcomes regarding the prevalence of potentially inadequate prescriptions. Outcomes: Four hospitals participated in the study, and 665 patients were included (342 in the control arm and 305 in the intervention arm). The mean age in the control arm was 78.2 years vs. 78.99 in the intervention arm. The total number of medications received by patients at the time of inclusion was 3 275. Of these, 9.3% (CI 95%: 8.3-10.4) were considered potentially inadequate prescriptions according to the STOPP criteria. On the other hand, 81.1% (CI 95%: 76.8-85.4) of the patients evaluated presented potentially inadequate prescriptions. Conclusion: This study has detected a high prevalence of potentially inadequate prescriptions in elderly patients attending the Emergency Department (AU)

Objetivo: Estimar la prevalencia de prescripciones potencialmente inapropiadas en pacientes mayores que acuden a urgencias Diseño: Ensayo clínico multicéntrico aleatorizado. Los pacientes mayores de 65 años que acuden a urgencias son asignados al grupo control o al de intervención. En el grupo de intervención, el farmacéutico revisa la medicación crónica de los pacientes e identifica aquellas prescripciones potencialmente inapropiadas de acuerdo a los criterios STOPP START. Los casos se discuten con el médico de urgencias y, cuando se considera indicado, se envía una recomendación al médico de atención primaria para que modifique el tratamiento. El grupo control recibe los cuidados habituales, que no incluyen una evaluación sistemática de la adecuación a los criterios STOPP START. En este artículo se presentan resultados preliminares respecto a la prevalencia de prescripciones potencialmente inapropiadas. Resultados: En el estudio han participado cuatro centros y se han incluido 665 pacientes (342 en el grupo control y 305 en el de intervención). La edad media en el grupo control ha sido de 78,2 años frente a 78,99 en el grupo de intervención. El número total de medicamentos que recibían los pacientes en el momento de la inclusión fue de 3.243. De estos, el 9,3% (IC 95%: 8,3-10,4) fueron considerados prescripciones potencialmente inapropiadas de tipo STOPP. Por otro lado, el 81,1%. (IC 95%: 76,8-85,4) de los pacientes evaluados presentaron prescripciones potencialmente inapropiadas. Conclusiones: En el estudio se ha detectado una alta prevalencia de prescripciones potencialmente inapropiadas en pacientes mayores que acuden a urgencias (AU)

A randomised controlled trial on the efficacy of a multidisciplinary health care team on morbidity and mortality of elderly patients attending the Emergency Department. Study design and preliminary results.

OBJECTIVE: To estimate the prevalence of potentially inadequate drug prescriptions in elderly patients who attend the Emergency Department. DESIGN: A multicentre randomized clinical trial. Patients over 65 years of age attending the Emergency Department are randomized to the control arm or the intervention arm. In the intervention arm, the pharmacist will review the chronic medication of patients and identify any potentially inadequate prescriptions, according to the STOPP-START criteria. The cases are discussed with the Emergency Specialist and, if considered adequate, a recommendation to modify the treatment is sent to the Primary Care Physician. The control arm will receive the standard of care, not including a systematic review of the adequacy to the STOPP-START criteria. This article presents preliminary outcomes regarding the prevalence of potentially inadequate prescriptions. OUTCOMES: Four hospitals participated in the study, and 665 patients were included (342 in the control arm and 305 in the intervention arm). The mean age in the control arm was 78.2 years vs. 78.99 in the intervention arm. The total number of medications received by patients at the time of inclusion was 3 275. Of these, 9.3% (CI 95%: 8.3-10.4) were considered potentially inadequate prescriptions according to the STOPP criteria. On the other hand, 81.1% (CI 95%: 76.8-85.4) of the patients evaluated presented potentially inadequate prescriptions. CONCLUSION: This study has detected a high prevalence of potentially inadequate prescriptions in elderly patients attending the Emergency Department.

Objetivo: Estimar la prevalencia de prescripciones potencialmente inapropiadas en pacientes mayores que acuden a urgencias Diseño: Ensayo clínico multicéntrico aleatorizado. Los pacientes mayores de 65 años que acuden a urgencias son asignados al grupo control o al de intervención. En el grupo de intervención, el farmacéutico revisa la medicación crónica de los pacientes e identifica aquellas prescripciones potencialmente inapropiadas de acuerdo a los criterios STOPP START. Los casos se discuten con el médico de urgencias y, cuando se considera indicado, se envía una recomendación al médico de atención primaria para que modifique el tratamiento. El grupo control recibe los cuidados habituales, que no incluyen una evaluación sistemática de la adecuación a los criterios STOPP START. En este artículo se presentan resultados preliminares respecto a la prevalencia de prescripciones potencialmente inapropiadas. Resultados: En el estudio han participado cuatro centros y se han incluido 665 pacientes (342 en el grupo control y 305 en el de intervención). La edad media en el grupo control ha sido de 78,2 años frente a 78,99 en el grupo de intervención. El número total de medicamentos que recibían los pacientes en el momento de la inclusión fue de 3.243. De estos, el 9,3% (IC 95%: 8,3-10,4) fueron considerados prescripciones potencialmente inapropiadas de tipo STOPP. Por otro lado, el 81,1%. (IC 95%: 76,8-85,4) de los pacientes evaluados presentaron prescripciones potencialmente inapropiadas. Conclusiones: En el estudio se ha detectado una alta prevalencia de prescripciones potencialmente inapropiadas en pacientes mayores que acuden a urgencias.

Medication Reconciliation in Oncological Patients: A Randomized Clinical Trial.

BACKGROUND: Medication reconciliation is considered to be an important strategy for increasing the safety of medication use. However, few studies have been carried out showing the effect of a medication reconciliation program on the incidence of reconciliation errors (REs) in oncological patients treated in the outpatient setting. OBJECTIVE: To measure the effect of a medication reconciliation program on the incidence of reconciliation error that reached the patient (RERP) in cancer patients receiving chemotherapy as outpatients. METHODS: A randomized, prospective, controlled study was carried out to identify the proportion of patients with at least 1 RERP. Medication reconciliation (intervention group) was compared with standard practice (control group) in patients starting new chemotherapy and who were receiving at least 1 home medication before the start of chemotherapy. A prespecified analysis of factors capable of influencing the occurrence of RE in oncological patients was also carried out. RESULTS: A total of 147 patients were included (76 in the intervention group and 71 controls) in this study. There were 3 (4%) patients with RERP (primary endpoint) in the intervention group and 21 (30%) patients in the control group (relative risk [RR] = 0.13, 95% CI = 0.04-0.43; P = 0.0009). The prespecified analysis of the effects of the Eastern Cooperative Oncology Group performance status (ECOG), Charlson Comorbidity Index score, and degree of poly-medication upon the number of patients with RE showed the Charlson Comorbidity Index to be unrelated to RE occurrence. However, the risk of RE was greater in patients with ECOG ≥ 2 (RR = 2.18, 95% CI = 1.4-3.4; P = 0.018) and among patients with major poly-medication (RR = 2.49, 95% CI = 1.52-4.09; P <0.001). CONCLUSIONS: Medication reconciliation results in a marked decrease in RERP in cancer patients. The factors that may influence RE occurrence in oncological patients have not been fully established, although parameters such as the degree of poly-medication and performance status may play a role. DISCLOSURES: No outside funding supported this study. The authors declare that they have no affiliations with or financial interests in any company, product, or service described in the manuscript. Study concept and design were contributed by Sierra-Sánchez, Martínez-Bautista, Baena-Cañada, and González-Carrascosa Vega. Martínez-Bautista, García-Martín, Suárez-Carrascosa, and González-Carrascosa Vega collected the data, which was interpreted by Sierra-Sánchez, Martínez-Bautista, Baena-Cañada, and González-Carrascosa Vega. The manuscript was written by Sierra-Sánchez and González-Carrascosa Vega and revised by Sierra-Sánchez, Martínez-Bautista, Baena-Cañada, and González-Carrascosa Vega.

Individualización de dosis en el paciente oncológico con insuficiencia hepática / Customization of doses in oncological patients with impaired hepatic function

Objetivo: determinar qué citostáticos requieren ajuste de dosis en pacientes con insuficiencia hepática. Métodos: se realizó una búsqueda en PubMed de toda la bibliografía publicada hasta julio de 2011 sobre dosificación de citostáticos en pacientes con función hepática alterada. Se procedió a su valoración según la clasificación de la Scottish Intercollegiate Guidelines Network. Se sintetizó un índice de fuerza de la recomendación farmacoterapéutica, para lo que se asoció el grado de recomendación de la evidencia encontrada y el número de pacientes incluidos en los estudios encontrados. Se clasificó la recomendación para cada fármaco como de fuerza alta, media o baja. Resultados: se encontraron un total de 46 publicaciones con información sobre dosificación en pacientes con insuficiencia hepática para un total de 17 citostáticos. El 67 por ciento (n= 31) de las publicaciones fueron estudios de cohortes con un nivel de evidencia 2+. No pudieron establecerse recomendaciones de fuerza alta, pero sí de fuerza moderada (76 por ciento; 13 fármacos) y baja (24 por ciento; 4 fármacos). Conclusiones: aunque el nivel de la evidencia disponible fue bajo, podrían establecerse recomendaciones sobre la dosificación de citostáticos en pacientes con insuficiencia hepática para mejorar la seguridad en el uso de estos fármacos en el referido grupo de enfermos(AU)

Objective: to determine the cytostatic drugs requiring dose adjustment in patients with impaired hepatic function. Methods: aliterature review of all the papers about dosage of cytostatic drug in patients with impaired hepatic function published till July 2011 in Pubmed search was made. They were assessed as rated by the Scottish Intercollegiate Guidelines Network. An index of pharmacotherapy recommendation strength was developed, for which the grade of recommendation of the evidence found and the number of patients included in the studies were then correlated, ranking the strength of recommendation for each drug as high, medium or low. Results: atotal of 46 publications with information about dosing in liver failure were found for 17 cytostatic drugs. Sixty seven percent (n= 31) of the publications were cohort studies with a level of evidence 2+. High strength recommendations could not been established, but moderate strength (76 percent; 13 drugs) and low strength (24 percent; 4 drugs) recommendations were finally established. Conclusions: although level of evidence was low, dosage recommendations of cytostatic drugs to be used in liver failure patients were established to improve safety in the use of these drugs in the stated group of patients(AU)