Efecto de la preinmunización sobre la eficacia terapéutica y toxicidad de la terapia génica antitumoral

“Efecto de la preinmunización con adenovirus sobre la eficacia terapéutica y toxicidad de la terapia gé- nica antitumoral” Objetivo: Determinar si la inyección intratumoral de adenovirus portadores de genes reporteros indu- ce, o no, la producción de anticuerpos en contra del vector, y establecer si la presencia de éstos influye en la efectividad terapéutica y toxicidad de la terapia génica del cáncer mediada por vectores adenovira- les. Resultados y conclusiones: En los animales no inmunizados, la diseminación de los vectores ade- novirales desde el sitio de la inyección es homogé- nea y de carácter sistémico. La preinmunización ocasiona una significativa reducción en el nivel y dura- ción de la expresión de luciferasa. Esta disminución es más importante en el hígado, comparada con la expresión dentro del tumor. El uso de dosis elevadas de vectores virales en animales con inmunidad pre- existente, restituye los niveles de expresión intratumoral a niveles comparables con los observados en animales controles. Sin embargo, los fenómenos de toxicidad hepática observados en los animales pre- inmunizados necesitan ser estudiados con más deta- lle, debido a las enormes implicaciones terapéuticas que los vectores adenovirales tienen en el tratamien- to del cáncer

Clinical and Resource Utilization Patterns in Patients with Refractory Neuropathic Pain Prescribed Pregabalin for the First Time in Routine Medical Practice in Primary Care Settings in Spain

Abstract Context and Objective. To describe clinical and resource utilization patterns in patients with refractory neuropathic pain (NeP) who were prescribed pregabalin for the first time in routine medical practice in primary care settings. Methods. Post-hoc analysis of a 12-week prospective observational study including pregabalin naïve adult patients with refractory chronic NeP of at least 6-months duration. Self-reported pain intensity, disability, sleep disturbances, symptoms of anxiety and depression, disability, health-related quality of life (HRQoL), health care resource utilization, and corresponding costs were assessed in this post-hoc analysis. Results. One thousand three hundred fifty-four patients were enrolled in the study, and three treatment groups were identified: 1) 598 patients replaced prior pain treatments with pregabalin as monotherapy; 2) 589 added pregabalin to their existing pain treatments; and 3) 167 other pain treatments were prescribed according with physician routine medical practice. Statistically significant differences were reported at baseline for intensity of pain, patient disability, severity of depressive symptoms, and HRQoL (P < 0.01 in all cases). No statistically significant differences were reported among the three treatment groups for anxiety bs_bs_banner Pain Medicine 2013; 14: 1954-1963 1954 severity or sleep disturbances. Subjects who received add-on pregabalin had greater use of direct and indirect resources vs the other groups, resulting in significantly higher quarterly overall costs per patient: €2,397 (2,308), €2,470 (1,857), and €3,110 (2,496), respectively (P < 0.001). Conclusion. These findings suggest that primary care physicians chose pregabalin as an option for treating refractory patients who tended to have much more severe NeP profiles, costing society more than when they chose other therapeutic strategies not including pregabalin

Rheological Behaviour of an Insoluble Lemon Fibre as Affected by Stirring, Temperature, Time and Storage

The final publication is available at link.springer.comIn this work, the effect the preparation method (two different stirring systems at two temperatures and times), fibre concentration (between 2% and 3%), temperature (between 10 °C and 50 °C) and storage time (between 24 h and 50 days at 5 °C) had on the flow properties of a suspension of dietary lemon fibre prepared with a 45° Brix sucrose solution were evaluated. This information will be helpful in order to discover the best possibilities of using fibre to increase the viscosity of certain kinds of products, depending on the processing, storage and consumption conditions. The obtained results indicate that all the aspects which contribute to increase component solubilisation and the interaction of the insoluble fraction with the aqueous phase when preparing the suspension, such as a decrease in particle size, a rise in temperature or a longer homogenization time, entail a higher apparent viscosity. Moreover, favoring the solubilisation in the preparation process leads to a more stable rheological behaviour of the suspension during storage. As expected, the apparent viscosity of suspensions was dependent on the shear rate, concentration and temperature. A thixotropic behaviour of fibre suspension was only observed at a very low shear rate (5 s -1). © 2010 Springer Science + Business Media, LLC.Córdoba Sequeira, A.; Camacho Vidal, MM.; Martínez Navarrete, N. (2012). Rheological Behaviour of an Insoluble Lemon Fibre as Affected by Stirring, Temperature, Time and Storage. Food and Bioprocess Technology. 5(3):1083-1092. doi:10.1007/s11947-010-0478-2S1083109253Akdogan, H., & McHugh, T.-H. (2000). Flow characterization of peach products during extrusion. Food Engineering and Physical Properties, 65(3), 471–475.Alonso, M.-L., Larrodé, O., & Zapico, J. (1995). Rheological behaviour of infant foods. Journal of Texture Studies, 26, 193–202.Duran, L., & Costell, E. (1982). Rheology of apricot puree: Characterization of flow. Journal of Texture Studies, 13, 43–58.Flint O (1996) Microscopía de los alimentos. Manual de métodos prácticos utilizando la miscroscopía óptica. Ed. Acribia S-A, Zaragoza, 28, 108–111Grigelmo-Miguel, N., Gorinstein, S., & Martín-Belloso, O. (1999a). Characterisation of peach dietary fiber concentrate as food ingredient. Food Chemistry, 65, 175–181.Grigelmo-Miguel, N., Ibarz-Ribas, A., & Martín-Belloso, O. (1999b). Rheology of peach dietary fibre suspensions. Journal of Food Engineering, 39, 91–99.Guerrero S-N & Alzamora S-M. (1998). Effect of pH, temperature and glucose addition on flow behaviour of fruit purées: II. Peach, papaya and mango purées. Journal of Food Engineering, 37, 77–101.Guillon, F., & Champ, M. (2000). Structural and physical properties of dietary fibres, and consequences of processing on human physiology. Food Research International, 33, 233–245.Hahn, S.-J., Ree, T., & Eyring, G.-H. (1959). Flow mechanism of thixotropic substances. Industrial and Engineering Chemistry Research, 51, 856–857.Jongaroontaprangsee, S., Tritrong, W., & Chokanaporn, W. (2007). Effects of drying temperature and particle size on hydration properties of dietary fiber powder from lime and cabbage by-products. International Journal of Food Properties, 10, 887–897.Lario, Y., Sendra, E., Garcıa-Perez, J., Fuentes, C., Sayas-Barbera, E., Fernández-López, J., et al. (2004). Preparation of high dietary fiber powder from lemon juice by-products. Innovation of Food Science Emerging Technologies, 5, 113–117.Mahmoud M-I & Fugitt M (1996) Rheological properties of a calorically dense nutritional supplement as a function of nitrogen source and dietary fiber. In: IFT Annual Meeting. Book of Abstracts. 80A-26, 183Mizrahi, S. (1979). A review of the physicochemical approach to the analysis of the structural viscosity of fluid fruit products. Journal of Texture Studies, 10, 67–82.Paredes, M.-D.-C., Rao, M.-A., & Bourne, M.-C. (1998). Rheological characterization of salad dressings: 1. Steady shear, thixotropy and effect of temperature. Journal of Texture Studies, 19, 247–258.Raghavendra, S.-N., Ramachandra Swamy, S.-R., Rastogi, N.-K., Raghavarao, K.-S.-M.-S., Kumar, S., & Tharanathan, R.-N. (2006). Grinding characteristics and hydration properties of coconut residue: A source of dietary fiber. Journal of Food Engineering, 72, 281–286.Sakata, T., & Saito, M. (2007). Insoluble dietary fiber of wheat bran increased viscosity of pig whole cecal contents in vitro. Journal of Nutrition Science and Vitaminology, 53(4), 380–381.Saldaña, S., Martínez-Navarrete, N., & Chiralt, A. (2000). Caracterización Reológica de Alimentos de alta viscosidad. In P. Fito, A. Chiralt, A. Andrés, & N. Martínez-Navarrete (Eds.), Series de Ciencia e Ingeniería de Alimentos. Investigación del postgrado del IAD-DTA. Vol I (p. 383). Valencia: Editorial de la Universidad Politécnica de Valencia.Sangnark, A., & Noomhorm, A. (2003). Effect of particle sizes on functional properties of dietary fibre prepared from sugarcane bagasse. Food Chemistry, 80(2), 221–229

Patient-reported-outcomes in subjects with painful lumbar or cervical radiculopathy treated with pregabalin: evidence from medical practice in primary care settings

The objective of this study was to evaluate the effect of pregabalin in painful cervical or lumbosacral radiculopathy treated in Primary Care settings under routine clinical practice. An observational, prospective 12-week secondary analysis was carried-out. Male and female above 18 years, naïve to PGB, with refractory chronic pain secondary to cervical/lumbosacral radiculopathy were enrolled. SF-MPQ, Sheehan Disability Inventory, MOS Sleep Scale, Hospital Anxiety and Depression Scale and the EQ-5D were administered. A total of 490 (34%) patients were prescribed PGB-monotherapy, 702 (48%) received PGB add-on, and 159 (11%) were administered non-PGB drugs. After 12 weeks, significant improvements in pain, associated symptoms of anxiety, depression and sleep disturbances, general health; and level of disability were observed in the three groups, being significantly greater in PGB groups. In routine medical practice, monotherapy or add-on pregabalin is associated with substantial pain alleviation and associated symptoms improvements in painful cervical or lumbosacral radiculopathy

Pharmaceutical pollution of the world's rivers

Environmental exposure to active pharmaceutical ingredients (APIs) can have negative effects on the health of ecosystems and humans. While numerous studies have monitored APIs in rivers, these employ different analytical methods, measure different APIs, and have ignored many of the countries of the world. This makes it difficult to quantify the scale of the problem from a global perspective. Furthermore, comparison of the existing data, generated for different studies/regions/continents, is challenging due to the vast differences between the analytical methodologies employed. Here, we present a global-scale study of API pollution in 258 of the world's rivers, representing the environmental influence of 471.4 million people across 137 geographic regions. Samples were obtained from 1,052 locations in 104 countries (representing all continents and 36 countries not previously studied for API contamination) and analyzed for 61 APIs. Highest cumulative API concentrations were observed in sub-Saharan Africa, south Asia, and South America. The most contaminated sites were in low- to middle-income countries and were associated with areas with poor wastewater and waste management infrastructure and pharmaceutical manufacturing. The most frequently detected APIs were carbamazepine, metformin, and caffeine (a compound also arising from lifestyle use), which were detected at over half of the sites monitored. Concentrations of at least one API at 25.7% of the sampling sites were greater than concentrations considered safe for aquatic organisms, or which are of concern in terms of selection for antimicrobial resistance. Therefore, pharmaceutical pollution poses a global threat to environmental and human health, as well as to delivery of the United Nations Sustainable Development Goals

The PREDICTS database: a global database of how local terrestrial biodiversity responds to human impacts

Biodiversity continues to decline in the face of increasing anthropogenic pressures such as habitat destruction, exploitation, pollution and introduction of alien species. Existing global databases of species’ threat status or population time series are dominated by charismatic species. The collation of datasets with broad taxonomic and biogeographic extents, and that support computation of a range of biodiversity indicators, is necessary to enable better understanding of historical declines and to project – and avert – future declines. We describe and assess a new database of more than 1.6 million samples from 78 countries representing over 28,000 species, collated from existing spatial comparisons of local-scale biodiversity exposed to different intensities and types of anthropogenic pressures, from terrestrial sites around the world. The database contains measurements taken in 208 (of 814) ecoregions, 13 (of 14) biomes, 25 (of 35) biodiversity hotspots and 16 (of 17) megadiverse countries. The database contains more than 1% of the total number of all species described, and more than 1% of the described species within many taxonomic groups – including flowering plants, gymnosperms, birds, mammals, reptiles, amphibians, beetles, lepidopterans and hymenopterans. The dataset, which is still being added to, is therefore already considerably larger and more representative than those used by previous quantitative models of biodiversity trends and responses. The database is being assembled as part of the PREDICTS project (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems – www.predicts.org.uk). We make site-level summary data available alongside this article. The full database will be publicly available in 2015

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

A Cost-Consequences analysis of the effect of Pregabalin in the treatment of peripheral Neuropathic Pain in routine medical practice in Primary Care settings

<p>Abstract</p> <p>Background</p> <p>Neuropathic pain (NeP) is a common symptom of a group of a variety of conditions, including diabetic neuropathy, trigeminal neuralgia, or postherpetic neuralgia. Prevalence of NeP has been estimated to range between 5-7.5%, and produces up to 25% of pain clinics consultations. Due to its severity, chronic evolution, and associated co-morbidities, NeP has an important individual and social impact. The objective was to analyze the effect of pregabalin (PGB) on pain alleviation and longitudinal health and non-health resources utilization and derived costs in peripheral refractory NeP in routine medical practice in primary care settings (PCS) in Spain.</p> <p>Methods</p> <p>Subjects from PCS were older than 18 years, with peripheral NeP (diabetic neuropathy, post-herpetic neuralgia or trigeminal neuralgia), refractory to at least one previous analgesic, and included in a prospective, real world, and 12-week two-visit cost-of-illness study. Measurement of resources utilization included both direct healthcare and indirect expenditures. Pain severity was measured by the Short Form-McGill Pain Questionnaire (SF-MPQ).</p> <p>Results</p> <p>One-thousand-three-hundred-fifty-four PGB-naive patients [58.8% women, 59.5 (12.7) years old] were found eligible for this secondary analysis: 598 (44%) switched from previous therapy to PGB given in monotherapy (PGBm), 589 (44%) received PGB as add-on therapy (PGB add-on), and 167 (12%) patients changed previous treatments to others different than PGB (non-PGB). Reductions of pain severity were higher in both PGBm and PGB add-on groups (54% and 51%, respectively) than in non-PGB group (34%), p < 0.001. Incremental drug costs, particularly in PGB subgroups [€34.6 (80.3), €160.7 (123.9) and €154.5 (133.0), for non-PGB, PGBm and PGBadd-on, respectively (p < 0.001)], were off-set by higher significant reductions in all other components of health costs yielding to a greater total cost reductions: -€1,045.3 (1,989.6),-€1,312.9 (1,543.0), and -€1,565.5 (2,004.1), for the three groups respectively (p = 0.03).</p> <p>Conclusion</p> <p>In Spanish primary care settings, PGB given either add-on or in monotherapy in routine medical practice was associated with pain alleviation leading to significant longitudinal reductions in resource use and total costs during the 12-week period of the study compared with non-PGB-therapy of patients with chronic NeP of peripheral origin. The use of non-appropriate analgesic therapies for neuropathic pain in a portion of subjects in non-PGB group could explain partially such findings.</p