Clinical and Economic Impact of a Multisciplinary Intervention to Reduce Bleeding Risk in Patients With Acute Coronary Syndrome.

INTRODUCTION AND OBJECTIVES: To evaluate the clinical and economic impact of a multidisciplinary program to reduce bleeding events in patients with acute coronary syndrome through optimization of antithrombotic therapy. METHODS: We designed a preintervention (PRE) and postintervention (POST) quasi-experimental study using a retrospective analysis of 2 cohorts. The first cohort was analyzed to detect correctable measures contributing to bleeding (PRE). Afterward, a quality improvement intervention with a bundle of recommendations was implemented. Finally, a second cohort of patients was evaluated to investigate the impact of the measures on bleeding reduction (POST). The impact on health outcomes was evaluated through comparison of the percentage of in-hospital bleeding events and 30-day readmissions between the 2 cohorts. The economic analysis took into account the costs associated with the implementation of the program and the cost-savings associated with the prevention of bleeding events and 30-day readmissions. RESULTS: A total of 677 patients were included (377 in PRE and 300 in POST). The total bleeding rate was reduced after the implementation of the bundled intervention by 29.2% (31.6% in POST vs 22.3% in PRE; OR, 0.62; 95%CI, 0.44-0.88) while 30-day readmission rates were 7.7% in PRE and 5% in POST (P=.20). The estimated avoided cost was €95 113.6 per year, meaning that €10.1 would be obtained in return for each euro invested during the first year and €36.3 during the following years. CONCLUSIONS: This multidisciplinary program has proven to be effective in reducing bleeding events and is economically attractive.

National Institutes of Health-Sponsored Clinical Islet Transplantation Consortium Phase 3 Trial: Manufacture of a Complex Cellular Product at Eight Processing Facilities.

Eight manufacturing facilities participating in the National Institutes of Health-sponsored Clinical Islet Transplantation (CIT) Consortium jointly developed and implemented a harmonized process for the manufacture of allogeneic purified human pancreatic islet (PHPI) product evaluated in a phase 3 trial in subjects with type 1 diabetes. Manufacturing was controlled by a common master production batch record, standard operating procedures that included acceptance criteria for deceased donor organ pancreata and critical raw materials, PHPI product specifications, certificate of analysis, and test methods. The process was compliant with Current Good Manufacturing Practices and Current Good Tissue Practices. This report describes the manufacturing process for 75 PHPI clinical lots and summarizes the results, including lot release. The results demonstrate the feasibility of implementing a harmonized process at multiple facilities for the manufacture of a complex cellular product. The quality systems and regulatory and operational strategies developed by the CIT Consortium yielded product lots that met the prespecified characteristics of safety, purity, potency, and identity and were successfully transplanted into 48 subjects. No adverse events attributable to the product and no cases of primary nonfunction were observed.

Salud percibida por las personas mayores en España en función del tipo de demanda de actividad física / Saúde percebida pelas pessoas mais velhas na Espanha de acordo com o tipo de demanda para a atividade física / Health perceived by older people in Spain regarding the type of physical activity demand

Actualmente asistimos a un lento e inevitable proceso de envejecimiento de la población. Este hecho convierte a las personas mayores en un grupo poblacional de excepcional interés para las investigaciones científicas. Uno de los objetivos mas presentes en la literatura es el de mejorar su salud y su calidad de vida, logrando un envejecimiento activo. Por ello, el objetivo principal de la presente investigación es conocer cómo perciben las personas mayores su salud en función del grupo de demanda de actividad física en el que se encuentran, estableciéndose, además, relaciones con las variables sociodemográficas. La metodología ha consistido en una encuesta seccional aplicada a una muestra estadísticamente representativa de personas mayores de 64 años en España. Los resultados muestran que las personas físicamente activas perciben mejor su estado de salud y que las diferencias sociodemográficas se reducen o invierten en este grupo.

We witness a slow and inevitable process of demographic aging of the population, which makes the elderly a population group of particular interest in our field of research. Literature focuses on improving their health and quality of life through active aging. For that reason, the main goal of this research was to learn how the elderly perceive their health regarding the different types of demand for physical activity, relating them to socio-demographic variables. The methodology consisted in a sectional survey applied to a statistically representative sample of over-64 seniors in Spain. The results suggest that physically active people have better perception of their health. Furthermore, socio-demographic differences were reduced or reverted in that group.

Assistimos atualmente a um processo lento e inevitável do envelhecimento da população no mundo. Esse fato converte as pessoas mais velhas em um grupo populacional de excepcional interesse para as investigações científicas. Um dos objetivos mais discutidos na literatura científica é procurar melhorar a saúde e a qualidade de vida, para assim obter um envelhecimento ativo. Então, o objetivo principal desta pesquisa é conhecer como as pessoas mais velhas percebem sua saúde de acordo com a demanda do grupo da atividade física que elas participam, além de estabelecer relações com as variáveis sócio-demográficas. A metodologia constituiu-se em um estudo seccional aplicado a uma amostra estatisticamente representativa de pessoas com mais de 64 anos na Espanha. Os resultados mostraram que as pessoas fisicamente ativas percebem melhor seu estado de saúde e as diferenças sócio-demográficas são reduzidas ou revertidas neste grupo.

Erythropoiesis-stimulating agents in anaemia due to chronic kidney disease: a cost-minimization analysis.

BACKGROUND: Some publications have shown that equivalent doses of erythropoiesis-stimulating agents (ESA) defined on label differ from those effective in clinical practice. Therefore, real costs could vary from theoretical costs in the treatment of anaemia in chronic kidney disease (CKD). OBJECTIVES: To perform a cost-minimization analysis to establish the economic impact of the principal ESAs used in treating anaemia secondary to CKD in daily practice. SECONDARY OBJECTIVES: to determine patient-month cost based on the erythropoietin resistance index (ERI); to analyze the difference in cost between pre-dialysis and peritoneal dialysis (PD) patients; and to analyze the association between iron deposits and ESA cost. SETTING: This study was carried out at 2 tertiary hospitals in Spain. METHOD: A multicentre cost-minimization analysis was performed in adult outpatients treated with ESAs for anaemia due to CKD. MAIN OUTCOME MEASURE: The primary outcome was the patient-month cost for each ESA. RESULTS: 409 patients were included. Median patient-month cost was: epoetin (103.2 [63.7, 187.8] euros), darbepoetin α (134.4 [67.2, 216.0] euros) and CERA (147.5 [98.3, 196.7] euros). Median patient-month cost according to ERI was: epoetin (1.60 [0.90, 2.60] euros/kg), darbepoetin α (2.01 [0.95, 3.48] euros/kg) and CERA (1.87 [1.33, 3.00] euros/kg). Median patient-month cost in pre-dialysis was 126.0 (73.7, 201.6) euros and in PD 153.0 (100.2, 275.4) euros. Median patient-month cost for patients with TSI < 20% was 147.5 (98.3, 224.9) euros compared to 100.9 (67.2, 196.7) euros which was the cost for patients with IST ≥ 20%. The median patient-month cost for patients with ferritin < 100 mcg/l was 134.4 (85.0, 201.6) euros compared to 100.8 (68.8, 196.7) euros, which was the cost for patients with ferritin ≥ 100 mcg/l (p = 0.242). CONCLUSION: Doses of CERA used in clinical practice are lower than those recommended on label, which directly influences cost and treatment efficiency. Cost stratification based on iron deposits has shown that patients with low TSI or ferritin require higher doses and consequently an associated higher cost. Thus, to guarantee adequate iron levels is essential in the rational use of ESAs.

High-quality gene assembly directly from unpurified mixtures of microarray-synthesized oligonucleotides.

To meet the growing demand for synthetic genes more robust, scalable and inexpensive gene assembly technologies must be developed. Here, we present a protocol for high-quality gene assembly directly from low-cost marginal-quality microarray-synthesized oligonucleotides. Significantly, we eliminated the time- and money-consuming oligonucleotide purification steps through the use of hybridization-based selection embedded in the assembly process. The protocol was tested on mixtures of up to 2000 oligonucleotides eluted directly from microarrays obtained from three different chip manufacturers. These mixtures containing <5% perfect oligos, and were used directly for assembly of 27 test genes of different sizes. Gene quality was assessed by sequencing, and their activity was tested in coupled in vitro transcription/translation reactions. Genes assembled from the microarray-eluted material using the new protocol matched the quality of the genes assembled from >95% pure column-synthesized oligonucleotides by the standard protocol. Both averaged only 2.7 errors/kb, and genes assembled from microarray-eluted material without clonal selection produced only 30% less protein than sequence-confirmed clones. This report represents the first demonstration of cost-efficient gene assembly from microarray-synthesized oligonucleotides. The overall cost of assembly by this method approaches 5¢ per base, making gene synthesis more affordable than traditional cloning.

Incidence, management and clinical outcomes of patients with airway complications following lung transplantation.

OBJECTIVE: Airway complications (AC) remain a significant contributing factor of morbidity after lung transplantation (LT). The aim of this study was to identify risk factors for AC, and to review the outcomes after endoscopic and surgical treatment. METHODS: From 1993 to 2006, 255 patients underwent LT. Seven retransplants and 34 patients not surviving beyond 7 days were excluded. The remaining patients were: 124 double LT (DLT), 85 single LT (SLT), 3 lobar LT and 2 liver-DLT, comprising 343 bronchial anastomoses at risk. Donor lungs were flushed with either modified Eurocollins or Perfadex. Bronchial anastomoses were telescoped when needed. Donor and recipient variables were recorded and analyzed by univariate and multivariate tests to identify risk factors for AC, and to assess differences between both complicated and non-complicated groups. RESULTS: Among 343 bronchial anastomoses, 31 presented AC (9%) in 27 patients (12.6%): 22 stenoses, 5 dehiscences, and 4 malacias, at 2.6+/-1.7 months post-transplant. Indications were 7 emphysema, 3 Alpha-1-antitrypsin deficiency, 12 cystic fibrosis (p=0.007), 4 pulmonary fibrosis, and 1 bronchiectasis. AC were observed in 4 SLT and 23 DLT (p=0.005). Incidence of AC did not differ between telescoped and non-telescoped anastomoses. By univariate analysis, AC were more frequent in grafts preserved with modified Eurocollins (p=0.033), CMV infection/disease (p=0.027) and airway colonizations post-transplant (p=0.021). Other donor and recipient variables did not differ between groups. By multivariate analysis, intubation longer than 72 h, DLT, and airway colonizations post-transplant remained independently associated with AC. Survival did not differ between groups. Most patients were successfully treated with endoscopic procedures; three required reoperation (lobectomy, pneumonectomy, retransplantation). AC related mortality was 1%. CONCLUSIONS: The incidence of AC after LT is 12.6% with a related mortality of 1%, irrespective of the technique of bronchial anastomosis performed. DLT, airway colonizations, and prolonged intubation post-transplant are associated with AC. Either endoscopic procedures or surgical therapy resolve these complications in most cases.

A Bayesian framework for comparative quantitative genetics.

Bayesian approaches have been extensively used in animal breeding sciences, but similar approaches in the context of evolutionary quantitative genetics have been rare. We compared the performance of Bayesian and frequentist approaches in estimation of quantitative genetic parameters (viz. matrices of additive and dominance variances) in datasets typical of evolutionary studies and traits differing in their genetic architecture. Our results illustrate that it is difficult to disentangle the relative roles of different genetic components from small datasets, and that ignoring, e.g. dominance is likely to lead to biased estimates of additive variance. We suggest that a natural summary statistic for G-matrix comparisons can be obtained by examining how different the underlying multinormal probability distributions are, and illustrate our approach with data on the common frog (Rana temporaria). Furthermore, we derive a simple Monte Carlo method for computation of fraternity coefficients needed for the estimation of dominance variance, and use the pedigree of a natural Siberian jay (Perisoreus infaustus) population to illustrate that the commonly used approximate values can be substantially biased.

Determinants and predictors of the cost of COPD in primary care: a Spanish perspective.

OBJECTIVES: 1) To estimate the annual cost of patients with stable chronic obstructive pulmonary disease (COPD) followed in primary care in Spain; 2) To analyze the possible cost predictor variables. PATIENTS AND METHODS: A multicenter, epidemiological, observational, descriptive study. Sociodemographic data, severity of disease, associated comorbidity, treatment followed by patients, quality of life (SF-12 questionnaire), health care resource utilization in the previous 12 months and duration of working disability due to COPD were collected. RESULTS: A total of 10,711 patients (75.6% men; 24.4% women) with a mean age of 67.1 +/- 9.66 years were evaluated. The mean forced expiratory volume in one second (FEV1) value was 57.4 +/- 13.4%. The total cost per patient per year was Euro1,922.60 +/- 2,306.44. The largest component of this cost was hospitalization (Euro788.72 +/- 1,766.65), followed by cost of drugs (Euro492.87 +/- 412.15) and visits to emergency rooms (Euro134.32 +/- 195.44). Linear regression analysis found associated heart disease, FEV1, physical component of quality of life, number of medical visits (primary care physician, pneumologist and emergency room), hospital admissions (frequency and duration of stay) and duration of working disability to be significant predictors of the total annual cost. CONCLUSIONS: The total annual cost of a COPD patient followed in primary care in Spain was considered high in this study. The presence of associated heart disease, severity of airflow obstruction, physical component of quality of life, health care resource utilization and duration of work disability were found to be predictor of cost.