Health-related quality of life impact of a triple combination of olmesartan medoxomil, amlodipine besylate and hydrochlorotiazide in subjects with hypertension

Background A post-hoc analysis was performed on the data from a 54 weeks phase III study (ClinicalTrials.gov identifier: NCT00923091) to measure changes in the health-related quality of life (HRQoL) of 2,690 patients aged ≥18 with moderate-to-severe hypertension who received one of six doses of olmesartan/amlodipine/hydrochlorothiazide (OLM/AML/HCTZ), using the MINICHAL and EQ-5D instruments. Methods Descriptive statistics were used to assess blood pressure and HRQoL scores over the study period. Analysis of covariance (ANCOVA) was used to identify those factors that could possibly have influenced HRQoL. Linear regression was used to assess the relationship between changes in blood pressure and HRQoL scores. Results Patients’ baseline MINICHAL mood and somatic domains scores were 5.5 and 2.6. Over the study period HRQoL improved as both MINICHAL scores decreased by 31-33%. Patients’ baseline EQ-5D index and VAS scores were 0.9 and 73.4 respectively, increasing by 6% and 12% over the study period. Patients’ QALY gain over the 54 weeks study period was estimated to be 0.029 QALYs. The ANCOVA showed that changes in patients’ HRQoL was likely to have been influenced by patients’ achievement of blood pressure control, the amount of concomitant medication and patients’ last used dosage strength of antihypertensive. Linear regression showed that blood pressure improvement may have been associated with improved HRQoL. Conclusions This study showed that OLM/AML/HCTZ reduced blood pressure and significantly increased blood pressure control whilst improving patients’ HRQoL. Achieving blood pressure control, amount of concomitant medication and dosage strength of antihypertensive impacted on patients’ HRQoL

Controlled Drug Delivery and Ophthalmic Applications

The goal of this paper is to present an overview of drug delivery from polymeric therapeutic lens to the anterior segment of the eye. Mathematical models that describe in vitro and in vivo drug delivery, from different types of lens, are presented. Healthy and pathological situations are addressed. Numerical simulations are included and compared with experimental results

Identifying and prioritising services in European terrestrial and freshwater ecosystems

Ecosystems are multifunctional and provide humanity with a broad array of vital services. Effective management of services requires an improved evidence base, identifying the role of ecosystems in delivering multiple services, which can assist policy-makers in maintaining them. Here, information from the literature and scientific experts was used to systematically document the importance of services and identify trends in their use and status over time for the main terrestrial and freshwater ecosystems in Europe. The results from this review show that intensively managed ecosystems contribute mostly to vital provisioning services (e.g. agro-ecosystems provide food via crops and livestock, and forests provide wood), while semi-natural ecosystems (e.g. grasslands and mountains) are key contributors of genetic resources and cultural services (e.g. aesthetic values and sense of place). The most recent European trends in human use of services show increases in demand for crops from agro-ecosystems, timber from forests, water flow regulation from rivers, wetlands and mountains, and recreation and ecotourism in most ecosystems, but decreases in livestock production, freshwater capture fisheries, wild foods and virtually all services associated with ecosystems which have considerably decreased in area (e.g. semi-natural grasslands). The condition of the majority of services show either a degraded or mixed status across Europe with the exception of recent enhancements in timber production in forests and mountains, freshwater provision, water/erosion/natural hazard regulation and recreation/ecotourism in mountains, and climate regulation in forests. Key gaps in knowledge were evident for certain services across all ecosystems, including the provision of biochemicals and natural medicines, genetic resources and the regulating services of seed dispersal, pest/disease regulation and invasion resistance

The International development of PROQOL-HCV: An instrument to assess the health-related quality of life of patients treated for Hepatitis C virus

Background Hepatitis C virus (HCV) compromises Health-related Quality of Life (HRQL) with detriments to Physical, Mental and Social health domains. Treatment with interferon and ribavirin is associated with side effects which further impair HRQL. New treatments appear potent, effective and tolerable. However, Patient Reported Outcomes instruments that capture the impact on HRQL for people with hepatitis C are largely non-specific and will be needed in the new treatment era. Therefore, we developed a conceptually valid multidimensional model of HCV-specific quality of life and pilot survey instrument, the Patient Reported Outcome Quality of Life survey for HCV (PROQOL-HCV). Methods HCV patients from France (n = 30), Brazil (n = 20) and Australia (n  = 20) were interviewed to investigate HCV-HRQL issues raised in the scientific literature and by treatment specialists. Interviews were recorded, transcribed and translated into English and French. Results Fifteen content dimensions were derived from the qualitative analysis, refined and fitted to four domains: (1) Physical Health included: fatigue, pain, sleep, sexual impairment and physical activity; (2) Mental Health: psychological distress, psychosocial impact, and cognition; (3) Social Health: support, stigma, social activity, substance use; (4) Treatment: management, side effects, and fear of treatment failure. The impact of some dimensions extended beyond their primary domain including: physical activity, cognition, sleep, sexual impairment, and the three treatment dimensions. A bank of 300 items was constructed to reflect patient reports and, following expert review, reduced to a 72-item pilot questionnaire. Conclusion We present a conceptually valid multidimensional model of HCV-specific quality of life and the pilot survey instrument, PROQOL-HCV. The model is widely inclusive of the experience of hepatitis C and the first to include the treatment dimension

Selective disruption of Tcf7l2 in the pancreatic β cell impairs secretory function and lowers β cell mass.

Type 2 diabetes (T2D) is characterized by β cell dysfunction and loss. Single nucleotide polymorphisms in the T-cell factor 7-like 2 (TCF7L2) gene, associated with T2D by genome-wide association studies, lead to impaired β cell function. While deletion of the homologous murine Tcf7l2 gene throughout the developing pancreas leads to impaired glucose tolerance, deletion in the β cell in adult mice reportedly has more modest effects. To inactivate Tcf7l2 highly selectively in β cells from the earliest expression of the Ins1 gene (∼E11.5) we have therefore used a Cre recombinase introduced at the Ins1 locus. Tcfl2(fl/fl)::Ins1Cre mice display impaired oral and intraperitoneal glucose tolerance by 8 and 16 weeks, respectively, and defective responses to the GLP-1 analogue liraglutide at 8 weeks. Tcfl2(fl/fl)::Ins1Cre islets displayed defective glucose- and GLP-1-stimulated insulin secretion and the expression of both the Ins2 (∼20%) and Glp1r (∼40%) genes were significantly reduced. Glucose- and GLP-1-induced intracellular free Ca(2+) increases, and connectivity between individual β cells, were both lowered by Tcf7l2 deletion in islets from mice maintained on a high (60%) fat diet. Finally, analysis by optical projection tomography revealed ∼30% decrease in β cell mass in pancreata from Tcfl2(fl/fl)::Ins1Cre mice. These data demonstrate that Tcf7l2 plays a cell autonomous role in the control of β cell function and mass, serving as an important regulator of gene expression and islet cell coordination. The possible relevance of these findings for the action of TCF7L2 polymorphisms associated with Type 2 diabetes in man is discussed

COMPILATION OF ACTIVE FAULT DATA IN PORTUGAL FOR USE IN SEISMIC HAZARD ANALYSIS

To estimate where future earthquakes are likely to occur, it is essential to combine information about past earthquakes with knowledge about the location and seismogenic properties of active faults. For this reason, robust probabilistic seismic hazard analysis (PSHA) integrates seismicity and active fault data. Existing seismic hazard assessments for Portugal rely exclusively on seismicity data and do not incorporate data on active faults. Project SHARE (Seismic Hazard Harmonization in Europe) is an EC-funded initiative (FP7) that aims to evaluate European seismic hazards using an integrated, standardized approach. In the context of SHARE, we are developing a fully-parameterized active fault database for Portugal that incorporates existing compilations, updated according to the most recent publications. The seismogenic source model derived for SHARE will be the first model for Portugal to include fault data and follow an internationally standardized approach. This model can be used to improve both seismic hazard and risk analyses and will be combined with the Spanish database for use in Iberian- and European-scale assessments

Estimação de magnitude da gravidade de quadros clínicos: um enfoque da psicofísica clínica

The severity of clinical illness was evaluated through the psychophysics method of magnitude estimation. The purpose of this experiment was: 1) to compare the scales derived from right judgement (magnitude estimation) used in three different Brazilian samples; 2) to verify the stability and agreement of severity estimations of clinical situations judged in Brazil, USA and England. In order to develop this study, professionals who work in the areas of psychology, nursing and medicine were invited. The lower coefficient of Pearson's correlation among the groups were of 0,88 the and the greater of 0,94. The exponents found between the Brazilian and American samples were of 1,22 and between the Brazilian and English samples of 1,15.En este experimento la gravedad de los cuadros clínicos fue evaluada a través del método psicofísico de estimación de magnitudes. Los objetivos de este experimento fueron: 1) comparar escalas derivadas de juzgamientos de razón (estimativas de magnitudes), hechos por tres diferentes muestras brasileñas; 2) verificar la estabilidad y la concordancia de las estimativas de la gravedad de cuadros clínicos juzgados en Brasil, EUA e Inglaterra. Así, fueron invitados profesionales actúan en las áreas de psicología, enfermería y medicina. El coeficiente de correlación de Pearson entre los grupos fue de 0,88 a menor y 0,94 a mayor. Los exponentes encontrados entre las muestras brasileñas y americanas fue de 1,22 y entre las muestras brasileñas e inglesas fue de 1,15.Neste experimento a gravidade de quadros clínicos foi avaliada através do método psicofísico de estimação de magnitudes. Os objetivos deste experimento foram: 1) Comparar as escalas derivadas de julgamentos de razão (estimativas de magnitudes) feitos por três diferentes amostras brasileiras; 2) Verificar a estabilidade e a concordância das estimativas da gravidade de quadros clínicos julgada no Brasil, E.U.A. e Inglaterra. Para tal foram convidados profissionais atuantes nas áreas de Psicologia, Enfermagem e Medicina. O coeficiente de correlação de Pearson entre os grupos foram de 0,92 a menor e 0,94 a maior. Os expoentes encontrados entre as amostras brasileira e americana foi de 1,22 e entre as amostras brasileira e inglesa foi de 1,15

Nutritional Evaluation Of Children With Chronic Cholestatic Disease

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)To evaluate the nutritional status of children with persistent cholestasis and to compare the anthropometric indices between children with and without liver cirrhosis and children with and without jaundice. Methods Children with persistent cholestasis, i.e. increased direct bilirrubin or changes in the canalicular enzyme gamma-glutamyl transferase (GGT), were included. The anthropometric measures were weight (W), height or length (H), arm circumference (AC), triceps skinfold thickness (TST), arm muscle circumference (AMC), and body mass index (BMI). Results Ninety-one children with cholestasis, with current median age of 12 months, were evaluated. W/age (A) and H/A indices below -2 Z-scores were observed in 33% and 30.8% of patients, respectively. Concerning the W/H index and BMI, only 12% and 16% of patients, respectively, were below -2 Z-scores. Regarding AC, 43.8% of 89 evaluated patients had some depletion. Observing the TST, 64% of patients had depletion, and 71.1% of the 45 evaluated patients had some degree of depletion regarding the ACM index. Conclusion Evaluation using weight in patients with chronic liver diseases may overestimate the nutritional status due to visceromegaly, subclinical edema, or ascites. Indices that correlate weight and height, such as W/H and BMI, may also not show depletion because of the chronic condition in which there are depletion of both weight and height. TST, AC, and ACM are parameters that better estimate nutritional status and should be part of the management of patients with liver diseases and cholestasis. © 2015 Sociedade Brasileira de Pediatria.922197205CNPq, Conselho Nacional de Desenvolvimento Científico e TecnológicoConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

Sward structure of marandu palisadegrass subjected to continuous stocking and nitrogen-induced rhythms of growth

Acceleration of the growth rhythm of plants using nitrogen fertiliser alters the rates of physiological processes like growth and senescence and may cause significant changes in sward structure, interfering with plant and animal responses. The objective of this experiment was to evaluate sward structure of marandu palisadegrass (Brachiaria brizantha) maintained at 30 cm under continuous stocking and subjected to contrasting rhythms of growth from January 2007 to April 2008. These were generated using or not nitrogen fertiliser, and comprised four experimental treatments as follows: control (non-fertilised), 150, 300 and 450 kg ha-1 of N. Acceleration of the growth rhythm of plants was associated with increases in leaf and stem bulk density, and resulted in larger LAI and total bulk density on swards subjected to faster (fertilised with 300 and 450 kg ha-1 of N) than those subjected to slower rhythms of growth (non-fertilised or fertilised with 150 kg ha-1 of N). Variations in dead material bulk density were associated with seasonal variations in climatic conditions, and were not influenced by growth rhythms. During autumn/winter and early spring (dry period of the year) swards subjected to faster, relative to those subjected to slower rhythms of growth, had larger proportion of leaves on the top horizons. On the other hand, sward structure did not vary among rhythms of growth at times of the year when there was no limitation in the availability of climatic growth factors (late spring and summer), indicating that when control of the grazing process is efficient, changes in sward structure are basically a function of seasonal variations in climatic growth conditions and phenological state of plants.A aceleração do ritmo de crescimento das plantas por meio da adubação nitrogenada altera a velocidade dos processos fisiológicos, atuando sobre o crescimento e a senescência, podendo refletir-se em alterações importantes sobre a estrutura do dossel. Avaliou-se a estrutura do dossel forrageiro de pastos de capim-marandu (Brachiaria brizantha) mantidos a 30 cm de altura por meio de lotação contínua e submetidos a ritmos de crescimento contrastantes de janeiro de 2007 a abril de 2008. Os distintos ritmos de crescimento foram criados por meio da utilização de adubação nitrogenada, segundo os tratamentos: sem adubação (controle), 150, 300 e 450 kg ha-1 de N. A aceleração do ritmo de crescimento dos pastos resultou em aumentos de densidade volumétrica de folhas e de colmos, refletindo em maior IAF e densidade volumétrica total em pastos submetidos aos ritmos de crescimento mais acelerados (adubados com 300 e 450 kg ha-1 de N) relativamente àqueles submetidos a ritmos de crescimento mais lentos (pastos não adubados e/ou adubados com 150 kg ha-1 de N). Variações em densidade volumétrica do material morto estiveram associadas a flutuações estacionais das condições climáticas, e não foram influenciadas pelos ritmos de crescimento avaliados. Na época da seca (outono/inverno e início de primavera), os pastos submetidos aos ritmos de crescimento mais acelerados apresentaram maior proporção de folhas no horizonte superior do dossel. Por outro lado, a estrutura do dossel não variou entre os ritmos de crescimento nas épocas de maior disponibilidade de fatores de crescimento (final de primavera e verão), indicando que quando o controle do processo de pastejo é feito de maneira eficiente, mudanças em estrutura são função basicamente de variações estacionais em condições climáticas e estádio fenológico das plantas

Efeitos da radiação gama na conservação de variedades de cebola ( Allium cepa) da região do São Francisco, Pernambuco

Three varieties of onion (Allium cepa), "Amarela das Canárias", "Pera de Pernambuco" and Asgrow, cultivated in the São Francisco River region (Pernambuco), were irradiated at doses of 4, 8 and 12 krad, and were stored in Recife, at ambient temperature. In this preliminary experiment, rotting, loss of weight and sprouting of onions were observed during 120 days. After this period, the mean conservation index, expressed as the percent of the initial number of bulbs, reached, for the former two varieties, values of 92, 94 and 83% corresponding to doses of 12, 8 and 4 krad, respectively; whereas the Asgrow variety exhibited a mean conservation index of 3%. The non irradiated Asgrow samples were at that time wholly spoiled. No sprouting was observed in the irradiated samples and the total loss of weight was more marked in the non-irradiated bulbs. The statistical analysis of experimental data indicated that irradiation conservation effects were significant at the 0,1% level for the "Amarela das Canárias" and "Pera de Pernambuco" varieties, as verified through the F-test. Moreover, the analysis of variance displayed no significance for the interaction effects between doses and varieties, and the loss of weight through dehydration, followed up to 55 days did not show differences at the usual significance levels.Três variedades de cebola, Amarela das Canárias, Pera de Pernambuco e Asgrow, bastante cultivadas na região do São Francisco, foram irradiadas com doses de 4, 8 e 12 krad e estocadas à temperatura ambiente, em Recife, PE, sendo observadas durante um período de 120 dias quanto à ocorrência de podridão, perda de peso e germinação. As percentagens médias de conservação após este período nas duas primeiras variedades foram de 92%, 94% e 83% para as doses de 12, 8 e 4 krad, e de apenas 3% para a variedade Asgrow. As testemunhas apresentaram conservação ao nível máximo de apenas 18%. Nenhuma germinação foi observada nas amostras irradiadas e a perda de peso foi mais acentuada nas não irradiadas. A análise estatística dos dados obtidos evidenciou que a conservação nas variedades Amarela das Canárias e Pera de Pernambuco foi significativa ao nível de 0,1% pelo teste F. A análise da variância não mostrou diferenças significativas entre os efeitos da interação dose versus variedade