Real-life experience in two cases of secondary prophylaxis with letermovir for CMV infection in solid organ transplantation.

IMPORTANCE: This observation provides comprehensive data on the clinical correlates of both cytomegalovirus (CMV) genotypic follow-up and clinical monitoring and outcomes for two different solid organ transplantation recipients that received letermovir as secondary prophylaxis. Our study emphasizes that monitoring of CMV disease in the patient and early genotypic detection of resistance mutations are essential when using new antiviral drugs for off-label indication in patients experiencing CMV relapses or not responding to standard antiviral therapy. These cases and the bibliography reviewed can be helpful for other researchers and clinicians working in the field to optimize the use of new treatments for transplant recipients since drug-resistant CMV infection is an important emerging problem even with new developments in antiviral treatment.

"Effect of calcifediol treatment and best available therapy versus best available therapy on intensive care unit admission and mortality among patients hospitalized for COVID-19: A pilot randomized clinical study".

OBJECTIVE: The vitamin D endocrine system may have a variety of actions on cells and tissues involved in COVID-19 progression especially by decreasing the Acute Respiratory Distress Syndrome. Calcifediol can rapidly increase serum 25OHD concentration. We therefore evaluated the effect of calcifediol treatment, on Intensive Care Unit Admission and Mortality rate among Spanish patients hospitalized for COVID-19. DESIGN: Parallel pilot randomized open label, double-masked clinical trial. SETTING: University hospital setting (Reina Sofia University Hospital, Córdoba Spain.) PARTICIPANTS: 76 consecutive patients hospitalized with COVID-19 infection, clinical picture of acute respiratory infection, confirmed by a radiographic pattern of viral pneumonia and by a positive SARS-CoV-2 PCR with CURB65 severity scale (recommending hospital admission in case of total score > 1). PROCEDURES: All hospitalized patients received as best available therapy the same standard care, (per hospital protocol), of a combination of hydroxychloroquine (400 mg every 12 h on the first day, and 200 mg every 12 h for the following 5 days), azithromycin (500 mg orally for 5 days. Eligible patients were allocated at a 2 calcifediol:1 no calcifediol ratio through electronic randomization on the day of admission to take oral calcifediol (0.532 mg), or not. Patients in the calcifediol treatment group continued with oral calcifediol (0.266 mg) on day 3 and 7, and then weekly until discharge or ICU admission. Outcomes of effectiveness included rate of ICU admission and deaths. RESULTS: Of 50 patients treated with calcifediol, one required admission to the ICU (2%), while of 26 untreated patients, 13 required admission (50 %) p value X2 Fischer test p < 0.001. Univariate Risk Estimate Odds Ratio for ICU in patients with Calcifediol treatment versus without Calcifediol treatment: 0.02 (95 %CI 0.002-0.17). Multivariate Risk Estimate Odds Ratio for ICU in patients with Calcifediol treatment vs Without Calcifediol treatment ICU (adjusting by Hypertension and T2DM): 0.03 (95 %CI: 0.003-0.25). Of the patients treated with calcifediol, none died, and all were discharged, without complications. The 13 patients not treated with calcifediol, who were not admitted to the ICU, were discharged. Of the 13 patients admitted to the ICU, two died and the remaining 11 were discharged. CONCLUSION: Our pilot study demonstrated that administration of a high dose of Calcifediol or 25-hydroxyvitamin D, a main metabolite of vitamin D endocrine system, significantly reduced the need for ICU treatment of patients requiring hospitalization due to proven COVID-19. Calcifediol seems to be able to reduce severity of the disease, but larger trials with groups properly matched will be required to show a definitive answer.

COVID and CARE@. Mobile application for monitoring SARS-CoV-2 positive patients after hospitalization / COVID and CARE@. Aplicación móvil para el seguimiento tras hospitalización de pacientes SARS-CoV-2 positivo

No disponible

Retrasplante pulmonar. Visión contraria / Lung Re-Transplantation. The Opposite View Point

No disponible

Budget impact analysis-principles of good practice: report of the ISPOR 2012 Budget Impact Analysis Good Practice II Task Force.

BACKGROUND: Budget impact analyses (BIAs) are an essential part of a comprehensive economic assessment of a health care intervention and are increasingly required by reimbursement authorities as part of a listing or reimbursement submission. OBJECTIVES: The objective of this report was to present updated guidance on methods for those undertaking such analyses or for those reviewing the results of such analyses. This update was needed, in part, because of developments in BIA methods as well as a growing interest, particularly in emerging markets, in matters related to affordability and population health impacts of health care interventions. METHODS: The Task Force was approved by the International Society for Pharmacoeconomics and Outcomes Research Health Sciences Policy Council and appointed by its Board of Directors. Members were experienced developers or users of BIAs; worked in academia and industry and as advisors to governments; and came from several countries in North America and South America, Oceania, Asia, and Europe. The Task Force solicited comments on the drafts from a core group of external reviewers and, more broadly, from the membership of the International Society for Pharmacoeconomics and Outcomes Research. RESULTS: The Task Force recommends that the design of a BIA for a new health care intervention should take into account relevant features of the health care system, possible access restrictions, the anticipated uptake of the new intervention, and the use and effects of the current and new interventions. The key elements of a BIA include estimating the size of the eligible population, the current mix of treatments and the expected mix after the introduction of the new intervention, the cost of the treatment mixes, and any changes expected in condition-related costs. Where possible, the BIA calculations should be performed by using a simple cost calculator approach because of its ease of use for budget holders. In instances, however, in which the changes in eligible population size, disease severity mix, or treatment patterns cannot be credibly captured by using the cost calculator approach, a cohort or patient-level condition-specific model may be used to estimate the budget impact of the new intervention, accounting appropriately for those entering and leaving the eligible population over time. In either case, the BIA should use data that reflect values specific to a particular decision maker's population. Sensitivity analysis should be of alternative scenarios chosen from the perspective of the decision maker. The validation of the model should include at least face validity with decision makers and verification of the calculations. Data sources for the BIA should include published clinical trial estimates and comparator studies for the efficacy and safety of the current and new interventions as well as the decision maker's own population for the other parameter estimates, where possible. Other data sources include the use of published data, well-recognized local or national statistical information, and, in special circumstances, expert opinion. Reporting of the BIA should provide detailed information about the input parameter values and calculations at a level of detail that would allow another modeler to replicate the analysis. The outcomes of the BIA should be presented in the format of interest to health care decision makers. In a computer program, options should be provided for different categories of costs to be included or excluded from the analysis. CONCLUSIONS: We recommend a framework for the BIA, provide guidance on the acquisition and use of data, and offer a common reporting format that will promote standardization and transparency. Adherence to these good research practice principles would not necessarily supersede jurisdiction-specific BIA guidelines but may support and enhance local recommendations or serve as a starting point for payers wishing to promulgate methodology guidelines.

Comorbilidades con impacto pronóstico tras el trasplante pulmonar / Comorbidities Impacting on Prognosis After Lung Transplant

Esta revisión pretende exponer de forma sucinta aquellas circunstancias clínicas previas al trasplante pulmonar que pueden repercutir negativamente en el pronóstico del trasplante a corto y largo plazo. Se plantean los métodos de rastreo y diagnóstico de comorbilidades comunes de impacto pronóstico negativo sobre el trasplante, tanto de patologías pulmonares como extrapulmonares, y se proponen medidas dirigidas a su corrección. La coordinación y el intercambio de información entre los centros que remiten a los candidatos y los centros trasplantadores permitirán detectar y corregir estas comorbilidades con el fin de minimizar los riesgos y de mejorar las expectativas de supervivencia de los pacientes trasplantados

The aim of this review is to give an overview of the clinical circumstances presenting before lung transplant that may have negative repercussions on the long and short-term prognosis of the transplant. Methods for screening and diagnosis of common comorbidities with negative impact on the prognosis of the transplant are proposed, both for pulmonary and extrapulmonary diseases, and measures aimed at correcting these factors are discussed. Coordination and information exchange between referral centers and transplant centers would allow these comorbidities to be detected and corrected, with the aim of minimizing the risks and improving the life expectancy of transplant receivers

Comorbidities impacting on prognosis after lung transplant.

The aim of this review is to give an overview of the clinical circumstances presenting before lung transplant that may have negative repercussions on the long and short-term prognosis of the transplant. Methods for screening and diagnosis of common comorbidities with negative impact on the prognosis of the transplant are proposed, both for pulmonary and extrapulmonary diseases, and measures aimed at correcting these factors are discussed. Coordination and information exchange between referral centers and transplant centers would allow these comorbidities to be detected and corrected, with the aim of minimizing the risks and improving the life expectancy of transplant receivers.

Reducción de tamaño del angiomiolipoma renal tras el tratamiento con everolimus en trasplante pulmonar por linfangioleiomiomatosis / Reduction in Size of Renal Angiomyolipoma after Treatment with Everolimus in Lung Transplantation due to Lymphangioleiomyomatosis

La linfangioleiomiomatosis (LAM) es una enfermedad rara caracterizada por la proliferación anormal de células musculares lisas inmaduras y una destrucción quística del pulmón, que condiciona el pronóstico de la enfermedad. Los angiomiolipomas renales suelen ser muy frecuentes en esta enfermedad, generalmente de curso asintomático, salvo complicaciones. Ante la ausencia de un tratamiento curativo, las últimas publicaciones reflejan resultados esperanzadores en la terapia molecular para evitar el deterioro funcional y el control del tamaño de los angiomiolipomas. Entre estas terapias destacan los inhibidores del complejo mTOR, sobre todo sirolimus. Presentamos un caso clínico de una paciente diagnosticada de LAM sometida a trasplante pulmonar con reducción del tamaño del angiomiolipoma renal tras el tratamiento con el inhibidor mTOR everolimus(AU)

Lymphangioleiomyomatosis (LAM) is a rare disease characterized by abnormal proliferation of immature smooth muscle cells and cystic lung destruction, which determines the prognosis of the disease. The kidney angiomyolipomas are usually very common in this disease and are usually asymptomatic unless complications arise. In the absence of a curative treatment, recent publications show promising results in molecular therapy to prevent functional decline and to control the size of the angiomyolipomas. These therapies include mTOR complex inhibitors, especially sirolimus. We report a case of a patient diagnosed with LAM who underwent lung transplantation with reduction of renal angiomyolipoma size after treatment with the mTOR inhibitor everolimus(AU)

Reduction in size of renal angiomyolipoma after treatment with everolimus in lung transplantation due to lymphangioleiomyomatosis.

Lymphangioleiomyomatosis (LAM) is a rare disease characterized by abnormal proliferation of immature smooth muscle cells and cystic lung destruction, which determines the prognosis of the disease. The kidney angiomyolipomas are usually very common in this disease and are usually asymptomatic unless complications arise. In the absence of a curative treatment, recent publications show promising results in molecular therapy to prevent functional decline and to control the size of the angiomyolipomas. These therapies include mTOR complex inhibitors, especially sirolimus. We report a case of a patient diagnosed with LAM who underwent lung transplantation with reduction of renal angiomyolipoma size after treatment with the mTOR inhibitor everolimus.

The use of cost per life year gained as a measurement of cost-effectiveness in Spain: a systematic review of recent publications.

OBJECTIVES: The objective of this study was to evaluate the methodological characteristics of cost-effectiveness evaluations carried out in Spain, since 1990, which include LYG as an outcome to measure the incremental cost-effectiveness ratio. METHODS: A systematic review of published studies was conducted describing their characteristics and methodological quality. We analyse the cost per LYG results in relation with a commonly accepted Spanish cost-effectiveness threshold and the possible relation with the cost per quality adjusted life year (QALY) gained when they both were calculated for the same economic evaluation. RESULTS: A total of 62 economic evaluations fulfilled the selection criteria, 24 of them including the cost per QALY gained result as well. The methodological quality of the studies was good (55%) or very good (26%). A total of 124 cost per LYG results were obtained with a mean ratio of 49,529 and a median of 11,490 (standard deviation of 183,080). Since 2003, a commonly accepted Spanish threshold has been referenced by 66% of studies. A significant correlation was found between the cost per LYG and cost per QALY gained results (0.89 Spearman-Rho, 0.91 Pearson). CONCLUSIONS: There is an increasing interest for economic health care evaluations in Spain, and the quality of the studies is also improving. Although a commonly accepted threshold exists, further information is needed for decision-making as well as to identify the relationship between the costs per LYG and per QALY gained.

Driving position field study, differences with the whiplash protocol and biomechanics experimental responses.

Rear-impact collisions at low speed are a leading cause of economic costs among motor vehicle accidents. Recently, EuroNCAP has incorporated in its protocol the whiplash test, to reproduce a low-speed rear impact. This paper presents a field driving study to assess the potential differences between the EuroNCAP dummy tests and actual drivers in the field, focusing on occupant position and biomechanics experimental results. A total of 182 drivers were randomly selected in two geographical areas in Spain. The driving position of each driver was recorded with a focus on the most relevant measurements for rear impact. Statistical analysis was performed to obtain means, standard deviations and density functions to compare observational seating position with that of the EuroNCAP testing protocol. The observational data showed a similar seatback angle to that used in the EuroNCAP protocol (24° in front of 25° for the protocol), a greater distance between the head vertex and the top of the head restraint (53mm compared to 39.5mm), and less distance between the occipital bone of the head and the headrest (67.9 compared to 89.3mm). Based on these data, 4 dummy tests were conducted using the dummy BioRID IIg. The baseline test was designed to reproduce the dummy position according to EuroNCAP 3.0 whiplash protocol. Three different additional tests were defined to reproduce the actual observed driving position as well as to assess a "worst case" scenario in terms of reduced seatback angle. These variations in initial driver position, comparing the EuroNCAP protocol to the observational study results, were not observed to cause significant differences in the biomechanical values measured in the BioRID IIg, The T1 acceleration was reduced less than 8%, the NIC was increased about 8%, and the NKm presented a reduction of 20%. Reducing the seat angle was observed to be more harmful in terms of NIC.

Esquemas innovadores de mejora del acceso al mercado de nuevas tecnologías: los acuerdos de riesgo compartido / Innovative patient access schemes for the adoption of new technology: risk-sharing agreements

La incorporación de nuevos tratamientos, procedimientos y tecnologías a la cartera de prestaciones de los sistemas de salud ha de cumplir un triple objetivo de modo equilibrado: mejora del acceso de los pacientes a soluciones innovadoras, sostenibilidad del sistema y compensación a la innovación. Sin embargo, los esquemas tradicionales basados en políticas de establecimiento de precios fijos, independientes de la adecuación de la utilización o del resultado final en condiciones de efectividad, pueden dar lugar a decisiones ineficientes. Recientemente, los acuerdos de riesgo compartido han aparecido como nuevos esquemas de acceso basados en resultados cuyo objetivo es reducir la incertidumbre de los diferentes agentes implicados, buscando un acuerdo en materia de financiación y de condiciones de uso de una tecnología sanitaria. Como elementos centrales del debate sobre su utilización se encuentran la variedad de instrumentos (de especial interés aquellos basados en resultados), las implicaciones para los distintos agentes involucrados en su diseño, y la supervisión y su posible aplicación en nuestro país. Como conclusión principal, los acuerdos de riesgo compartido deberían de ser unos esquemas de acceso al mercado a utilizar en casos muy concretos, cuando las condiciones estándar de acceso no puedan ser aplicables debido a la incertidumbre de resultados a largo plazo en condiciones de efectividad. Asimismo, estas medidas no están orientadas sólo a regular el precio sino también a actuar sobre la adecuación en la utilización, si bien, dada la experiencia internacional, es pronto para llegar a una conclusión sólida sobre los resultados de su aplicación (AU)

The incorporation of new treatments, procedures and technologies into the services’ portfolio of healthcare providers should aim to improve three areas equally: patient access to innovative solutions, the sustainability of the health system and compensation for innovation. However, traditional schemes based on fixed prices that fail to consider the product’s appropriacy of use or its results in terms of effectiveness may lead to inefficient decision-making processes. Recently, risk-sharing agreements have appeared as new access schemes based on results that aim to reduce the uncertainty of the distinct health care players involved in reaching an agreement on new health technology financing and conditions of use. Key elements in the debate on these instruments are the huge variety of instruments available (especially those based on results), the implications for different players involved in their design and supervision, and their possible implementation in Spain. Our main conclusion is that risk-sharing agreements should be used in highly limited cases when standard conditions of access cannot be applied due to uncertainty about long-term effectiveness. These measures are aimed not only at regulating price but also at acting on the appropriate use of new technology. However, because international experience is limited, drawing a solid conclusion on the final results of the application of risk-sharing agreements would be premature (AU)

[Innovative patient access schemes for the adoption of new technology: risk-sharing agreements]. / Esquemas innovadores de mejora del acceso al mercado de nuevas tecnologías: los acuerdos de riesgo compartido.

The incorporation of new treatments, procedures and technologies into the services' portfolio of healthcare providers should aim to improve three areas equally: patient access to innovative solutions, the sustainability of the health system and compensation for innovation. However, traditional schemes based on fixed prices that fail to consider the product's appropriate use or its results in terms of effectiveness may lead to inefficient decision-making processes. Recently, risk-sharing agreements have appeared as new access schemes based on results that aim to reduce the uncertainty of the distinct health care players involved in reaching an agreement on new health technology financing and conditions of use. Key elements in the debate on these instruments are the huge variety of instruments available (especially those based on results), the implications for different players involved in their design and supervision, and their possible implementation in Spain. Our main conclusion is that risk-sharing agreements should be used in highly limited cases when standard conditions of access cannot be applied due to uncertainty about long-term effectiveness. These measures are aimed not only at regulating price but also at acting on the appropriate use of new technology. However, because international experience is limited, drawing a solid conclusion on the final results of the application of risk-sharing agreements would be premature.

Análisis de coste-utilidad del manejo de la fibrilación auricular concomitante en España / Cost-utility analysis of concomitant atrial fibrillation management in Spain

ObjetivosLa fibrilación auricular (FA) es la arritmia más común en la práctica clínica; es un factor de riesgo de accidente cerebrovascular (ACV), y está asociada a una importante morbilidad y mortalidad. Nuestro objetivo fue realizar un análisis de coste-utilidad de las diferentes opciones de tratamiento en pacientes >40 años con FA concomitante con valvulopatía mitral en España, desde la perspectiva del Sistema Nacional de Salud.MétodosSe realizó una evaluación económica mediante un modelo de Markov con cuatro estados de salud (ritmo sinusal, FA, ACV dependiente, muerte) simulando una cohorte de 1.000 pacientes en cada opción de tratamiento más cirugía de válvula mitral (tratamiento farmacológico, ablación quirúrgica y ablación por catéter). El horizonte temporal fue de 5 años, con ciclos de 3 meses. Los datos de costes y efectos se obtuvieron de la revisión de la literatura y de la opinión de expertos clínicos, descontados al 3,5% anual. Se realizó un análisis de sensibilidad probabilístico para determinar la robustez de nuestros resultados.ResultadosLos años de vida ajustados por calidad (AVAC) ganados fueron 3,29, 3,89 y 3,83, respectivamente, para las alternativas de no ablación, ablación quirúrgica y ablación por catéter. Los costes por paciente fueron de 5.770€, 10.034€ y 11.289€, respectivamente. La razón coste/AVAC de ablación quirúrgica frente a no ablación fue de 7.145€. La ablación quirúrgica resultó dominante frente a la ablación por catéter. El análisis probabilístico de sensibilidad mostró que los resultados del modelo fueron robustos.ConclusionesLa ablación quirúrgica es una opción de tratamiento coste-efectiva en los pacientes con FA concomitante, con una razón coste-efectividad por debajo del umbral de eficiencia comúnmente aceptado en España(AU)

ObjectivesAtrial fibrillation (AF) is the most common arrhythmia in clinical practice; this disorder is a risk factor for stroke and is associated with substantial morbidity and mortality. Our objective was to develop a cost-utility analysis of the different treatment alternatives in patients aged 40 years old or more with concomitant AF with valve disease in Spain, from the National Health System perspective.MethodsAn economic evaluation through a Markov model with four health states (sinus rhythm, AF, dependent stroke, death) was developed to simulate the evolution of a cohort of 1,000 patients receiving each treatment alternative in addition to mitral valve surgery (drug therapy, surgical ablation and catheter ablation). The time horizon was 5 years, with a cycle length of 3 months. Data on costs and effects were obtained from the published literature and expert opinion and were discounted at 3.5%. A sensitivity analysis was developed to determine the robustness of the results.ResultsThe quality-adjusted life years (QALY) gained were 3.29, 3.89, and 3.83, respectively, for the alternatives of no ablation, surgical ablation and catheter ablation. The costs per patient were 5,770€, 10,034€ and 11,289€, respectively. The surgical ablation cost/QALY rate compared with no ablation was 7,145€. Surgical ablation was dominant versus catheter ablation. The probabilistic sensitivity analysis showed that the results were robust.ConclusionsSurgical ablation is a cost-effective treatment option in patients with concomitant AF, with a cost-effectiveness ratio under the efficiency threshold commonly accepted in Spain(AU)

[Cost-benefit analysis of concomitant atrial fibrillation management in Spain]. / Análisis de coste-utilidad del manejo de la fibrilación auricular concomitante en España.

OBJECTIVES: Atrial fibrillation (AF) is the most common arrhythmia in clinical practice; this disorder is a risk factor for stroke and is associated with substantial morbidity and mortality. Our objective was to develop a cost-utility analysis of the different treatment alternatives in patients aged 40 years old or more with concomitant AF with valve disease in Spain, from the National Health System perspective. METHODS: An economic evaluation through a Markov model with four health states (sinus rhythm, AF, dependent stroke, death) was developed to simulate the evolution of a cohort of 1,000 patients receiving each treatment alternative in addition to mitral valve surgery (drug therapy, surgical ablation and catheter ablation). The time horizon was 5 years, with a cycle length of 3 months. Data on costs and effects were obtained from the published literature and expert opinion and were discounted at 3.5%. A sensitivity analysis was developed to determine the robustness of the results. RESULTS: The quality-adjusted life years (QALY) gained were 3.29, 3.89, and 3.83, respectively, for the alternatives of no ablation, surgical ablation and catheter ablation. The costs per patient were 5,770euro, 10,034euro and 11,289euro, respectively. The surgical ablation cost/QALY rate compared with no ablation was 7,145euro. Surgical ablation was dominant versus catheter ablation. The probabilistic sensitivity analysis showed that the results were robust. CONCLUSIONS: Surgical ablation is a cost-effective treatment option in patients with concomitant AF, with a cost-effectiveness ratio under the efficiency threshold commonly accepted in Spain.