Determining the value contribution of emicizumab (Hemlibra®) for the prophylaxis of haemophilia A with inhibitors in Spain by multi-criteria decision analysis

Haemophilia A; Inhibitors; Drug valueHemofilia A; Inhibidores; Valores del medicamentoHemofília A; Inhibidors; Valors del medicamentPatients with moderate to severe haemophilia A are at a higher risk of developing FVIII inhibitors that require the use of more costly and less effective treatments. The objective of this study was to determine the value of emicizumab for the prophylaxis of haemophilia A with inhibitors compared to the current therapeutic alternatives, activated prothrombin complex concentrate and recombinant factor VIIa through reflective Multi-Criteria Decision Analysis. The EVIDEM framework adapted to orphan drugs and weighted by a sample of 98 national and regional Spanish evaluators was used. Two structured evidence matrices were developed: emicizumab against activated prothrombin complex concentrate and emicizumab against recombinant factor VIIa. A multidisciplinary team of haemophilia experts rated each of the criteria. Mean and standard deviation were calculated by each criterion and discussed among all participants. Haemophilia A with inhibitors was perceived as a severe disease with high unmet needs. Emicizumab was rated with higher efficacy, therapeutic benefit and quality of life than comparators. When administered alone for the prevention of bleeding events, emicizumab had slightly better safety and tolerability profile than activated prothrombin complex concentrate and similar with recombinant factor VIIa. The inclusion of emicizumab in clinical practice guidelines was valued positively by the members of the panel. Overall, value of emicizumab was higher than activated prothrombin complex concentrate and recombinant factor VIIa, mostly because of efficacy and therapeutic benefit in reducing treated haemorrhages. Reflective Multi-Criteria Decision Analysis has proven to be a feasible method to determine the value contribution of comparative therapies in haemophilia.This work was supported by Hoffmann-La Roche

Hospital pharmacy initiatives for improving the management of patients with congenital coagulopathies

Congenital coagulopathies; Hospital pharmacyCoagulopatías congénitas; Farmacia hospitalariaCoagulopaties congènites; Farmàcia hospitalàriaObjetivo: Identificar e impulsar iniciativas orientadas a la mejora del manejo de los pacientes con coagulopatías congénitas por parte de farmacia hospitalaria en el contexto sanitario español. Método: Se identificaron, evaluaron y priorizaron, por parte de un panel de farmacéuticos especialistas en farmacia hospitalaria, iniciativas para la mejora de la atención a los pacientes con coagulopatías congénitas. La priorización se realizó en base a la valoración de su impacto y factibilidad en una escala del 1 al 5. Una vez obtenida la priorización de las iniciativas, las de mayor puntuación se agruparon en tres grandes líneas de actuación. Resultados: Se identificaron siete áreas de actividad en las que el papel de los farmacéuticos especialistas en farmacia hospitalaria resulta clave para el manejo del paciente con coagulopatías congénitas: coordinación con el equipo asistencial de pacientes con coagulopatías congénitas; evaluación y selección de medicamentos; dispensación; información y formación al paciente; seguimiento farmacoterapéutico; investigación e innovación en estas patologías; formación y capacitación continuada del farmacéutico especialista en farmacia hospitalaria. Se consideraron prioritarias 15 iniciativas por tener una puntuación media de impacto ≥ 3,8 y factibilidad ≥ 3,2. Así, el 29,4% de las iniciativas priorizadas pertenecen al ámbito asistencial, el 23,5% a información y formación al paciente, el 11,8% a evaluación y selección de medicamentos, el 11,8% al seguimiento farmacoterapéutico, el 11,8% a iniciativas transversales, el 5,9% a dispensación y el 5,9% a investigación e innovación en el campo de las coagulopatías congénitas, mientras que las iniciativas referentes a la formación y capacitación a profesionales no resultaron priorizadas. Conclusiones: Se han propuesto tres grandes líneas de actuación basadas en las iniciativas identificadas como altamente prioritarias por un panel de 16 expertos farmacéuticos especialistas en farmacia hospitalaria para el manejo de pacientes con coagulopatías congénitas. Estas iniciativas se basan en acciones concretas y pueden llevarse a cabo desde los servicios de farmacia hospitalaria, por lo que se cree que podrán llegar a tener un impacto real en el contexto sanitario español.Objective: To identify and promote initiatives aimed at improving the management by hospital pharmacists of patients with congenital coagulopathies in the Spanish healthcare context. Method: A series of initiatives to improve the care of patients with congenital coagulopathies were identified, evaluated, and prioritized by a panel of hospital pharmacists. Prioritization was based on an assessment of each initiative’s impact and feasibility on a scale of 1 to 5. Once initiatives were prioritized, those assigned the highest priority were grouped into three action areas. Results: Seven areas of activity were identified in which the role of hospital pharmacists is key for the management of patients with congenital coagulopathies: coordination with the healthcare team; drug evaluation and selection; dispensing; patient information and education; pharmacotherapeutic follow-up; research and innovation in the field of congenital coagulopathies; and capacity-building and training of hospital pharmacists. Fifteen initiatives were considered a priority, with an average impact score ≥ 3.8 and a feasibility score ≥ 3.2. A total of, 29.4% of the prioritized initiatives corresponded to healthcare, 23.5% to patient information and education, 11.8% to drug evaluation and selection, 11.8% to phar macotherapeutic monitoring, 11.8% to cross-sectional initiatives, 5.9% to dispensing and 5.9% to research and innovation in the field of congenital coagulopathies: In contrast, initiatives related to capacity-building and training were not prioritized. Conclusions: Three main action areas were proposed based on the initiatives identified as high priority for the management of patients with congenital coagulopathies by a panel of 16 hospital pharmacists. Action areas revolved around specific activities that hospital pharmacy departments can undertake to contribute to improving the healthcare situation in Spain.Para la realización de este trabajo se ha contado con el patrocinio de CSL-Behring en el marco del proyecto con código 108858

Consensus recommendations for the improvement of inter- and intra-centre care coordination in the management of hemophilia

Hemofilia A; Equipo multidisciplinar; TelefarmaciaHaemophilia A; Multidisciplinary care team; TelepharmacyHemofilia A; Equip multidisciplinar; TelefarmàciaObjetivo definir las recomendaciones consensuadas para mejorar la coordinación asistencial entre Farmacia Hospitalaria, Hematología y Enfermería, inter e intra-centros, en la atención a los pacientes con hemofilia. Método se identificaron y valoraron las recomendaciones para la mejora de la coordinación asistencial en el abordaje de los pacientes con hemofilia, por parte de un panel multidisciplinar de profesionales con experiencia en este campo (Farmacia Hospitalaria, Hematología y Enfermería) y apoyado en la evidencia científica. La valoración de las recomendaciones identificadas se realizó por metodología de consenso Rand/UCLA (Delphi-adaptado) con base en su adecuación y, posteriormente, a su necesidad. En ambos casos, se empleó la escala ordinal de Likert. Los datos se analizaron estadísticamente a través de diferentes métricas. Resultados se identificaron 53 recomendaciones para la mejora de la coordinación asistencial entre Farmacia Hospitalaria, Hematología y Enfermería en el manejo del paciente con hemofilia, agrupadas en 8 ámbitos de actuación: i) Unidades de Hemofilia, centros de referencia y abordaje multidisciplinar; ii) papel de Hematología, Farmacia Hospitalaria y Enfermería en el recorrido asistencial de los pacientes con hemofilia; iii) telefarmacia y telemedicina; iv) monitorización farmacocinética; v) transición al régimen de paciente adulto; vi) educación sanitaria al paciente; vii) cirugía, urgencias e ingreso hospitalario; y viii) evaluación de los resultados. Todas las recomendaciones fueron valoradas por el panel de expertos externos como adecuadas y necesarias. Conclusiones el recorrido asistencial del paciente con hemofilia es complejo y depende de diversas variables. Además, requiere la implicación de distintos profesionales sanitarios que deben actuar de manera coordinada e integrada en todas las etapas de la vida del paciente, de manera adaptada a sus necesidades individuales. Las recomendaciones identificadas y consensuadas pueden suponer una mejora para la continuidad y calidad asistencial, pues facilitan la integración y coordinación de los profesionales implicados en el abordaje de esta enfermedad, especialmente de Farmacia Hospitalaria, Hematología y Enfermería.Objective Define consensus recommendations to improve care coordination between Hospital Pharmacy, Haematology and Nursing, inter- and intra-center, in the care of haemophilia patients. Method Recommendations for the improvement of care coordination in the management of haemophilia patients were identified and assessed by a multidisciplinary panel of professionals with experience in this field (Hospital Pharmacy, Haematology and Nursing) and supported by scientific evidence. The identified recommendations were assessed by Rand/UCLA consensus methodology (Delphi-adapted) based on their appropriateness and, subsequently, on their necessity. In both cases, it was used ordinal Likert scale. Data were statistically analysed through different metrics. Results Fifty-three recommendations for the improvement of care coordination between Hospital Pharmacy, Haematology and Nursing in the management of haemophilia patients were identified, grouped into eight areas of action: i) Haemophilia units, reference centers and multidisciplinary care; ii) Role of Haematology, Hospital Pharmacy and Nursing in the patient journey of haemophilia patients; iii) Telepharmacy and telemedicine; iv) Pharmacokinetic monitoring; v) Transition to adult patient regimen; vi) Patient health education; vii) Surgery, emergency room and hospital admission; and viii) Outcome evaluation. All recommendations were assessed as appropriate and necessary by the external expert panel. Conclusions Haemophilia patient journey is complex and depends on different variables. It also requires the involvement of different healthcare professionals who must act in a coordinated and integrated manner at all stages of the patient's life, adapted to their individual needs. On this matter, the identified and agreed recommendations may improve continuity and quality of care, as they facilitate the integration and coordination of the professionals involved in the management of this pathology, especially Hospital Pharmacy, Haematology and Nursing.Para la realización de este trabajo se ha contado con el patrocinio de CSL-Behring

HTLV-1 infection in solid organ transplant donors and recipients in Spain

HTLV-1 infection is a neglected disease, despite infecting 10-15 million people worldwide and severe illnesses develop in 10% of carriers lifelong. Acknowledging a greater risk for developing HTLV-1 associated illnesses due to immunosuppression, screening is being widely considered in the transplantation setting. Herein, we report the experience with universal HTLV testing of donors and recipients of solid organ transplants in a survey conducted in Spain. All hospitals belonging to the Spanish HTLV network were invited to participate in the study. Briefly, HTLV antibody screening was performed retrospectively in all specimens collected from solid organ donors and recipients attended since the year 2008. A total of 5751 individuals were tested for HTLV antibodies at 8 sites. Donors represented 2312 (42.2%), of whom 17 (0.3%) were living kidney donors. The remaining 3439 (59.8%) were recipients. Spaniards represented nearly 80%. Overall, 9 individuals (0.16%) were initially reactive for HTLV antibodies. Six were donors and 3 were recipients. Using confirmatory tests, HTLV-1 could be confirmed in only two donors, one Spaniard and another from Colombia. Both kidneys of the Spaniard were inadvertently transplanted. Subacute myelopathy developed within 1 year in one recipient. The second recipient seroconverted for HTLV-1 but the kidney had to be removed soon due to rejection. Immunosuppression was stopped and 3 years later the patient remains in dialysis but otherwise asymptomatic. The rate of HTLV-1 is low but not negligible in donors/recipients of solid organ transplants in Spain. Universal HTLV screening should be recommended in all donor and recipients of solid organ transplantation in Spain. Evidence is overwhelming for very high virus transmission and increased risk along with the rapid development of subacute myelopathy

Inward and Outward FDI Country Profiles, Second Edition

This second edition contains a series of 77 standardized country profiles dealing with the inward and outward foreign direct investment (FDI) performance of 40 economies. The profiles have been peer-reviewed by a global network of experts. The publication is intended to contribute to the analysis of trends in foreign direct investment and policy issues related to them. More specifically, the individual profiles discuss FDI trends and developments (country-level developments, the corporate players); effects of the recent global crises; and the policy scene. Each profile contains a standard set of tables, including on FDI stocks and flows, sectoral and geographical FDI distributions, the largest M&As and greenfield investments, the principal foreign affiliates (for inward FDI), and the principal multinational enterprises (for outward FDI). The standardized template used to produce the profiles allows cross-country comparisons. The volume is meant to be a reference tool for anyone interested in foreign direct investment

Determining the value contribution of emicizumab (Hemlibra®) for the prophylaxis of haemophilia A with inhibitors in Spain by multi-criteria decision analysis

Haemophilia A; Inhibitors; Drug valueHemofilia A; Inhibidores; Valores del medicamentoHemofília A; Inhibidors; Valors del medicamentPatients with moderate to severe haemophilia A are at a higher risk of developing FVIII inhibitors that require the use of more costly and less effective treatments. The objective of this study was to determine the value of emicizumab for the prophylaxis of haemophilia A with inhibitors compared to the current therapeutic alternatives, activated prothrombin complex concentrate and recombinant factor VIIa through reflective Multi-Criteria Decision Analysis. The EVIDEM framework adapted to orphan drugs and weighted by a sample of 98 national and regional Spanish evaluators was used. Two structured evidence matrices were developed: emicizumab against activated prothrombin complex concentrate and emicizumab against recombinant factor VIIa. A multidisciplinary team of haemophilia experts rated each of the criteria. Mean and standard deviation were calculated by each criterion and discussed among all participants. Haemophilia A with inhibitors was perceived as a severe disease with high unmet needs. Emicizumab was rated with higher efficacy, therapeutic benefit and quality of life than comparators. When administered alone for the prevention of bleeding events, emicizumab had slightly better safety and tolerability profile than activated prothrombin complex concentrate and similar with recombinant factor VIIa. The inclusion of emicizumab in clinical practice guidelines was valued positively by the members of the panel. Overall, value of emicizumab was higher than activated prothrombin complex concentrate and recombinant factor VIIa, mostly because of efficacy and therapeutic benefit in reducing treated haemorrhages. Reflective Multi-Criteria Decision Analysis has proven to be a feasible method to determine the value contribution of comparative therapies in haemophilia.This work was supported by Hoffmann-La Roche

2023 GEIS Guidelines for gastrointestinal stromal tumors

Gastrointestinal stromal tumor (GIST) is the most common malignant neoplasm of mesenchymal origin. GIST spans a wide clinical spectrum that ranges from tumors with essentially no metastatic potential to malignant and life-threatening spread diseases. Gain-of-function mutations in KIT or PDGFRA receptor tyrosine kinases are the crucial drivers of most GISTs, responsible for tumor initiation and evolution throughout the entire course of the disease. The introduction of tyrosine kinase inhibitors targeting these receptors has substantially improved the outcomes in this formerly chemoresistant cancer. As of today, five agents hold regulatory approval for the treatment of GIST: imatinib, sunitinib, regorafenib, ripretinib, and avapritinib. This, in turn, represents a success for a rare neoplasm. During the past two decades, GIST has become a paradigmatic model in cancer for multidisciplinary work, given the disease-specific particularities regarding tumor biology and tumor evolution. Herein, we review currently available evidence for the management of GIST. This clinical practice guideline has been developed by a multidisciplinary expert panel (oncologist, pathologist, surgeon, molecular biologist, radiologist, and representative of patients' advocacy groups) from the Spanish Group for Sarcoma Research, and it is conceived to provide, from a critical perspective, the standard approach for diagnosis, treatment, and follow-up

Bioavailability of once-daily tacrolimus formulations used in clinical practice in the management of De Novo kidney transplant recipients: the better study

Multicenter, prospective, observational study to compare the relative bioavailability of once-daily tacrolimus formulations in de novo kidney transplant recipients. De novo kidney transplant recipients who started a tacrolimus-based regimen were included 14 days post-transplant and followed up for 6 months. Data from 218 participants were evaluated: 129 in the LCPT group (Envarsus) and 89 in the PR-Tac (Advagraf) group. Patients in the LCPT group exhibited higher relative bioavailability (Cmin /total daily dose [TDD]) vs. PR-Tac (61% increase; P < .001) with similar Cmin and 30% lower TDD levels (P < .0001). The incidence of treatment failure was 3.9% in the LCPT group and 9.0% in the PR-Tac group (P = .117). Study discontinuation rates were 6.2% in the LCPT group and 12.4% in the PR-Tac group (P = .113). Adverse events, renal function and other complications were comparable between groups. The median accumulated dose of tacrolimus in the LCPT group from day 14 to month 6 was 889 mg. Compared to PR-Tac, LCPT showed higher relative bioavailability, similar effectiveness at preventing allograft rejection, comparable effect on renal function, safety, adherence, treatment failure and premature discontinuation rates

Engineering Interpenetrating Polymer Networks of Poly(2-Hydroxyethyl Acrylate) as Ex Vivo Platforms for Articular Cartilage Regeneration

A hydrogel based on interpenetrating polymer networks (IPNs) has been designed to act as a platform in an articular cartilage bioreactor for the ex vivo test of scaffolds, simulating the host tissue. Poly(2-hydroxyethyl acrylate) (PHEA) has been mechanically reinforced by its interpenetration with poly(ethyl acrylate). The resulting IPNs are phase separated systems with a porosity that increases with the amount of PHEA. Compression Young s modulus decreases and permeability increases when increasing the PHEA content in the samples, being the IPN with a 79% of PHEA the best candidate to mimic articular cartilage.The authors gratefully acknowledge the financial support from the Spanish Ministry of Economy and Competitiveness through the MAT2013-46467-C4-1-R and MAT2013-46467-C4-3-R projects (including the FEDER financial support), the FPU AP2010/2557 and the FPI BES-2011-046144 PhD grants, and the CIBER-BBN. CIBER-BBN is an initiative funded by the VI National R&D&I Plan 2008-2011, Iniciativa Ingenio 2010, Consolider Program. CIBER Actions are financed by the Instituto de Salud Carlos III with assistance from the European Regional Development Fund. The translation of this paper was funded by the Universitat Politecnica de Valencia, Spain.Poveda Reyes, S.; Gamboa Martínez, TC.; Manzano, S.; Doweidar, MH.; Gómez Ribelles, JL.; Ochoa Garrido, I.; Gallego Ferrer, G. (2015). Engineering Interpenetrating Polymer Networks of Poly(2-Hydroxyethyl Acrylate) as Ex Vivo Platforms for Articular Cartilage Regeneration. International Journal of Polymeric Materials and Polymeric Biomaterials. 64(14):745-754. https://doi.org/10.1080/00914037.2014.1002132S745754641