Contribución al estudio de los concentrados de factor VIII de la coagulación

[spa] Los concentrados de factor VIII constituyen el instrumento terapéutico fundamental en el tratamiento de la hemofilia A. En esta memoria se han valorado los parámetros farmacotécnicos, contenido en proteínas, estabilidad del factor tras la reconstitución y farmacocinética tras la administración a pacientes afectos de hemofilia A. Los parámetros farmacotécnicos varían según el preparado comercial, aunque todos pueden ser considerados aptos para su empleo terapéutico. El contenido en proteínas plasmáticas contaminantes varía según el preparado entre 1.47 VI/mg. proteína y un valor superior a 1070 VI/mg. Únicamente una especialidad es útil para el tratamiento de la enfermedad de Von Willebrand, dado que además del factor VIII contiene una actividad funcional apreciable de factor Von Willebrand. La estabilidad del factor VIII varía según el preparado y sigue una cinética de orden 0. En cualquier caso, todas las especialidades son estables, al menos, durante 24 horas. El factor VIII no se adapta a un modelo farmacocinético compartimental único, por lo que requiere, sobre todo en estudios comparativos, un análisis amodelístico. Los parámetros farmacocinéticos varían según el preparado y según la forma de administración. La administración de factor VIII en perfusión continua presenta las mejores aptitudes desde el punto de vista farmacocinético

El consumo de cannabis y derivados en la provincia de Barcelona : analítica de las muestras aprehendidas

Tesi de Llicenciatura per a la obtenció del Grau de Farmàcia. Facultat de Farmàcia. Universitat de Barcelona. Director: Carmen de la Torre Boronat, Rafael Codony Salcedo. 1983

Positive Outcomes Influence the Rate and Time to Publication, but Not the Impact Factor of Publications of Clinical Trial Results

Objectives: Publication bias may affect the validity of evidence based medical decisions. The aim of this study is to assess whether research outcomes affect the dissemination of clinical trial findings, in terms of rate, time to publication, and impact factor of journal publications. Methods and Findings: All drug-evaluating clinical trials submitted to and approved by a general hospital ethics committee between 1997 and 2004 were prospectively followed to analyze their fate and publication. Published articles were identified by searching Pubmed and other electronic databases. Clinical study final reports submitted to the ethics committee, final reports synopses available online and meeting abstracts were also considered as sources of study results. Study outcomes were classified as positive (when statistical significance favoring experimental drug was achieved), negative (when no statistical significance was achieved or it favored control drug) and descriptive (for non-controlled studies). Time to publication was defined as time from study closure to publication. A survival analysis was performed using a Cox regression model to analyze time to publication. Journal impact factors of identified publications were recorded. Publication rate was 48·4% (380/785). Study results were identified for 68·9% of all completed clinical trials (541/785). Publication rate was 84·9% (180/212) for studies with results classified as positive and 68·9% (128/186) for studies with results classified as negative (p<0·001). Median time to publication was 2·09 years (IC95 1·61-2·56) for studies with results classified as positive and 3·21 years (IC95 2·69-3·70) for studies with results classified as negative (hazard ratio 1·99 (IC95 1·55-2·55). No differences were found in publication impact factor between positive (median 6·308, interquartile range: 3·141-28·409) and negative result studies (median 8·266, interquartile range: 4·135-17·157). Conclusions: Clinical trials with positive outcomes have significantly higher rates and shorter times to publication than those with negative results. However, no differences have been found in terms of impact factor

Long-term effectiveness of cinacalcet in non-dialysis patients with chronic kidney disease and seconday hyperparathyroidism

Background: secondary hyperparathyroidism (SHPT) is a common complication of chronic kidney disease (CKD). Cinacalcet use is controversial in non-dialysis patients. Methods: this retrospective observational study recruited patients receiving cinacalcet (off-label use) in 2010 and 2011. Patients were followed for three years from the beginning of treatment using an intention-to-treat approach. Results: forty-one patients were studied: 14 CKD stage 3 (34.1%), 21 CKD stage 4 (51.2%), and 6 CKD stage 5 (14.6%). Median baseline parathyroid hormone (PTH) was 396 (101-1,300) pg/mL. Upon cinacalcet treatment (22 ± 12 months), PTH levels decreased by ≥ 30% in 73.2% of patients (P < 0.001; 95% confidence interval [CI], 59-87%), with a mean time for response of 18.7 months (95% CI, 15.4-22.1). Sixteen patients were followed for 36 months and treated for 32 ± 9 months. Mean reduction in their PTH levels was 50.1% (P < 0.001; 95% CI, 33.8-66.4%) at 36 months, with 62.5% of patients (P < 0.001; 95% CI, 35.9-89.1%) presenting reductions of ≥ 30%. Serum calcium levels decreased from 9.95 ± 0.62 mg/dL to 9.21 ± 0.83 and 9.12 ± 0.78 mg/dL at 12 and 36 months, respectively (P < 0.001). Serum phosphorus levels increased from 3.59 ± 0.43 to 3.82 ± 0.84 at 12 months (P = 0.180), remaining so at 36 months (P = 0.324). At 12 and 36 months, 2 (12.5%) patients experienced hypocalcemia. Meanwhile, 1 (6.3%) and 4 (25.0%) patients reported hyperphosphatemia at 12 and 36 months, respectively. Conclusion: Cinacalcet remained effective for at least 36 months in non-dialysis patients with SHPT. Electrolytic disturbances were managed with concurrent use of vitamin D and its analogs or phosphate binders

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

Effectiveness of Cinacalcet in Patients with Chronic Kidney Disease and Secondary Hyperparathyroidism Not Receiving Dialysis.

Background Secondary hyperparathyroidism (SHPT) is a common complication in chronic kidney disease (CKD) patients. Cinacalcet could be a therapeutic option although its use is controversial in patients not receiving dialysis. Thus, the aim of this study is to assess the effectiveness and safety of cinacalcet in patients with CKD and SHPT without renal replacement treatment (RRT) and without renal transplantation (RT). Methods A retrospective observational study was conducted. Patients were included if they had collected cinacalcet, under off-label use, during 2010 and 2011. Patients selected were followed from the beginning of cinacalcet therapy for one year of treatment. Results A total of 37 patients were included with CKD stage 3 (38%), 4 (51%) and 5 (11%). Baseline mean PTH value was 400.86 ± 168.60 mg/dl. At 12 months, a 67% of patients achieved at least a 30% reduction in their PTH value (p<0.001; CI 49.7-83.6), and the overall mean reduction of PTH values was 38% (p< 0.001; IC -49.1, -27.5). A 28% of the patients achieved KDOQI PTH goals (p = 0.003, CI 12%-50%). At 12 months, mean serum calcium values decreased by 6% and mean serum phosphorus values increased by 13%. A 19% of patients experienced hypocalcemia episodes while an increase of 24% in hyperphosphatemia episodes was observed. A 25% of patients finished cinacalcet before a year of treatment. Main withdrawal reasons were: gastrointestinal and other discomfort (8%), hypocalcaemia (8%), non-compliance (3%), interactions (3%) and excess of efficacy (3%). Conclusions Cinacalcet was effective in patients with CKD and SHPT not receiving dialysis. Electrolytic imbalances could be managed with administration of vitamin D and analogues or phosphate binders

COVID-19’s impact on care practice for alpha-1-antitrypsin deficiency patients

Alpha-1-antitrypsin deficiency; COVID-19; Patient managementDeficiencia de alfa-1-antitripsina; COVID-19; Gestión del pacienteDeficiència d'alfa-1-antitripsina; COVID-19; Gestió del pacientBackground Patients with alpha-1 antitrypsin deficiency (AATD), commonly categorized as a rare disease, have been affected by the changes in healthcare management brought about by COVID-19. This study’s aim was to identify the changes that have taken place in AATD patient care as a result of the COVID-19 pandemic in Spain and to propose experts’ recommendations aimed at ensuring humanized and quality care for people with AATD in the post-pandemic situation. Methods A qualitative descriptive case study with a holistic single-case design was conducted, using focus groups with experts in AATD clinical management, including 15 health professionals with ties to the Spanish health system (12 pneumologists and 2 hospital pharmacists from 11 different hospitals in Spain) and 1 patient representative. Results COVID-19 has had a major impact on numerous aspects of AATD clinical patient management in Spain, including diagnostic, treatment, and follow-up phases. The experts concluded that there is a need to strengthen coordination between Primary Care and Hospital Care and improve the coordination processes across all the organizations and actors involved in the healthcare system. Regarding telemedicine and telecare, experts have concluded that it is necessary to promote this methodology and to develop protocols and training programs. Experts have recommended developing personalized and precision medicine, and patient participation in decision-making, promoting self-care and patient autonomy to optimize their healthcare and improve their quality of life. The possibility of monitoring and treating AATD patients from home has also been proposed by experts. Another result of the study was the recommendation of the need to ensure that plasma donations are made on a regular basis by a sufficient number of healthy individuals. Conclusion The study advances knowledge by highlighting the challenges faced by health professionals and changes in AATD patient management in the context of the COVID-19 pandemic. It also proposes experts’ recommendations aimed at ensuring humanized and quality care for people with AATD in the post-pandemic situation. This work could serve as a reference study for physicians on their daily clinical practice with AATD patients and may also provide guidance on the changes to be put in place for the post-pandemic situation.This study was funded by CSL Behring

Topical administration of bosentan prevents retinal neurodegeneration in experimental diabetes

Experimental evidence suggests that endothelin 1 (ET-1) is involved in the development of retinal microvascular abnormalities induced by diabetes. The effects of ET-1 are mediated by endothelin A- and B-receptors (ETA and ETB). Endothelin B-receptors activation mediates retinal neurodegeneration but there are no data regarding the effectiveness of ETB receptor blockage in arresting retinal neurodegeneration induced by diabetes. The main aim of the present study was to assess the usefulness of topical administration of bosentan (a dual endothelin receptor antagonist) in preventing retinal neurodegeneration in diabetic (db/db) mice. For this purpose, db/db mice aged 10 weeks were treated with one drop of bosentan (5 mg/mL, n = 6) or vehicle (n = 6) administered twice daily for 14 days. Six non-diabetic (db/+) mice matched by age were included as the control group. Glial activation was evaluated by immunofluorescence using specific antibodies against glial fibrillary acidic protein (GFAP). Apoptosis was assessed by TUNEL method. A pharmacokinetic study was performed in rabbits. We found that topical administration of bosentan resulted in a significant decrease of reactive gliosis and apoptosis. The results of the pharmacokinetic study suggested that bosentan reached the retina through the trans-scleral route. We conclude that topical administration of bosentan was effective in preventing neurodegeneration in the diabetic retina and, therefore, could be a good candidate to be tested in clinical trials

Spanish Consensus Statement on alternatives to allogeneic blood transfusion: the 2013 update of the 'Seville Document'

Summary of recommendations on alternatives to reduce allogeneic blood transfusion (in descending order of strength)..