Network meta-analysis of biologic treatments for psoriasis using absolute Psoriasis Area and Severity Index values ≤1, 2, 3 or 5 derived from a statistical conversion method.

BACKGROUND: In practice, the goal of treatment for patients with psoriasis is to achieve almost clear or clear skin and maintain disease control, regardless of baseline disease severity. However, identifying absolute Psoriasis Area and Severity Index (PASI) values for new treatment goals is challenging, as most clinical trials report relative PASI 50, 75, 90 or 100 improvements but rarely absolute PASI values achieved. OBJECTIVE: Our objective was to illustrate a statistical conversion method that was developed to derive absolute PASI values from available clinical trial data on relative PASI improvements. The results of network meta-analyses (NMAs) based on these derived data were then compared with those of NMAs based on the corresponding relative PASI improvement data for selected biologics for moderate-to-severe psoriasis. METHODS: The PASI statistical conversion method was applied to relative PASI improvement data for 11 biologic treatment regimens and placebo at 12 weeks using data from 50 published studies. The respective proportions of patients reaching absolute PASI values ≤1, 2, 3 or 5 were then calculated. Frequentist NMAs (Rücker method) were subsequently used to compare efficacy results across relative and absolute PASI data. RESULTS: The ranking of included treatment regimens for patients achieving absolute PASI 0 to 8 was aligned with results for relative PASI scores (from 100 to 60) at end of induction therapy. Across the range of PASI scores considered, the most effective treatment regimens based on both absolute and relative PASI NMAs were brodalumab 210 mg every 2 weeks and ixekizumab 80 mg every 2 weeks, followed by guselkumab 100 mg every 8 weeks and risankizumab 150 mg every 12 weeks. CONCLUSION: Data generated using this mathematical model will be useful to inform ongoing scientific discussions on treatment goals in the absence of primary absolute PASI data for all available treatments for moderate-to-severe plaque psoriasis.

Evaluación de la eficiencia de los tratamientos biológicos en la psoriasis moderada a grave en España: análisis de coste por número necesario a tratar (NNT) / A Cost-per-Number Needed to Treat Analysis Assessing the Efficiency of Biologic Drugs in Moderate to Severe Plaque Psoriasis

Antecedentes y objetivos: La psoriasis es una enfermedad inflamatoria crónica de la piel cuya prevalencia en España se estima en el 2,3% de la población y en la que alrededor del 30% de los pacientes tienen formas moderadas a graves. El tratamiento con agentes biológicos está suponiendo un avance en el manejo de la enfermedad, aunque también representa un reto económico. El objetivo de este estudio es determinar la eficiencia, en términos de coste por número necesario a tratar (NNT), de las terapias biológicas disponibles en España para el tratamiento de la psoriasis en placas moderada a grave. Métodos: Los datos de NNT se obtuvieron de un metaanálisis en red que incluía todos los ensayos clínicos aleatorizados con medicamentos biológicos comercializados en España. Los costes de cada terapia se calcularon según las posologías aprobadas en las fichas técnicas para el primer año de tratamiento. A partir de estos datos se calculó el coste por NNT de los fármacos para los distintos niveles de PASI (75, 90 y 100). Se realizó un análisis de sensibilidad considerando solamente el periodo de medición de la respuesta PASI (de 10 a 16 semanas) según el tratamiento. Resultados: Para la respuesta PASI 75, el orden de terapias de mayor a menor eficiencia es ixekizumab > ustekinumab 45 mg > ustekinumab 90 mg > secukinumab > infliximab > etanercept > adalimumab. Para la respuesta PASI 90, el orden es ixekizumab > secukinumab > ustekinumab 45 mg > ustekinumab 90 mg > infliximab > adalimumab > etanercept. Para la respuesta PASI 100 el orden es ixekizumab > secukinumab > infliximab > ustekinumab 90 mg > ustekinumab 45 mg > adalimumab > etanercept. El análisis de sensibilidad mostró algún cambio en el orden de las secuencias para el periodo de evaluación de la respuesta. Conclusiones: Este análisis muestra una relación entre la eficacia de los tratamientos biológicos disponibles en España para el tratamiento de la psoriasis en placas moderada a grave y su eficiencia, siendo ixekizumab el que mostró un menor coste por NNT en todos los niveles de respuesta PASI alcanzados (75, 90 y 100) para el primer año de tratamiento

Background and objectives: Psoriasis is a chronic inflammatory skin disease with an estimated prevalence in Spain of 2.3% of the population. Approximately 30% of patients have moderate-to-severe forms. Treatment with biologic agents is proving to be a step forward in the management of the disease, although these treatments are very expensive. The objective of this study was to determine the efficiency, in terms of cost per number needed to treat (NNT), of the biologic drugs available in Spain for the treatment of moderate to severe plaque psoriasis. Methods: NNT data were obtained from a network meta-analysis that included all randomized clinical trials of biologic drugs sold in Spain. The cost of each treatment was calculated based on the approved dosage for the first year of treatment, as indicated in the Summary of Product Characteristics. These data were used to calculate the cost per NNT of the drugs for various PASI scores (75, 90, and 100). A sensitivity analysis was performed taking into consideration only the PASI-response measurement time (after 10, 12, or 16 weeks, depending on the drug). Results: The order of efficiency, from most to least efficient, in the case of a PASI 75 response was ixekizumab > ustekinumab 45 mg > ustekinumab 90 mg > secukinumab > infliximab > etanercept > adalimumab. The order for PASI 90 was ixekizumab >secukinumab >ustekinumab 45 mg > ustekinumab 90 mg > infliximab > adalimumab > etanercept. The order for PASI 100 was ixekizumab > secukinumab > infliximab > ustekinumab 90 mg > ustekinumab 45 mg > adalimumab > etanercept. The sensitivity analysis showed some changes in the order, depending on the response-assessment period. Conclusions: The findings show a link between the efficacy of the biologic therapies available in Spain for the treatment of moderate-to-severe plaque psoriasis and their efficiency. Ixekizumab had the lowest cost per NNT for all PASI-response scores (75, 90, and 100) during the first year of treatment

A Cost-per-Number Needed to Treat Analysis Assessing the Efficiency of Biologic Drugs in Moderate to Severe Plaque Psoriasis. / Evaluación de la eficiencia de los tratamientos biológicos en la psoriasis moderada a grave en España: análisis de coste por número necesario a tratar (NNT).

BACKGROUND AND OBJECTIVES: Psoriasis is a chronic inflammatory skin disease with an estimated prevalence in Spain of 2.3% of the population. Approximately 30% of patients have moderate-to-severe forms. Treatment with biologic agents is proving to be a step forward in the management of the disease, although these treatments are very expensive. The objective of this study was to determine the efficiency, in terms of cost per number needed to treat (NNT), of the biologic drugs available in Spain for the treatment of moderate to severe plaque psoriasis. METHODS: NNT data were obtained from a network meta-analysis that included all randomized clinical trials of biologic drugs sold in Spain. The cost of each treatment was calculated based on the approved dosage for the first year of treatment, as indicated in the Summary of Product Characteristics. These data were used to calculate the cost per NNT of the drugs for various PASI scores (75, 90, and 100). A sensitivity analysis was performed taking into consideration only the PASI-response measurement time (after 10, 12, or 16 weeks, depending on the drug). RESULTS: The order of efficiency, from most to least efficient, in the case of a PASI 75 response was ixekizumab > ustekinumab 45mg > ustekinumab 90mg > secukinumab > infliximab > etanercept > adalimumab. The order for PASI 90 was ixekizumab >secukinumab >ustekinumab 45mg > ustekinumab 90mg > infliximab > adalimumab > etanercept. The order for PASI 100 was ixekizumab > secukinumab > infliximab > ustekinumab 90mg > ustekinumab 45mg > adalimumab > etanercept. The sensitivity analysis showed some changes in the order, depending on the response-assessment period. CONCLUSIONS: The findings show a link between the efficacy of the biologic therapies available in Spain for the treatment of moderate-to-severe plaque psoriasis and their efficiency. Ixekizumab had the lowest cost per NNT for all PASI-response scores (75, 90, and 100) during the first year of treatment.

Comparison of ixekizumab with ustekinumab in moderate-to-severe psoriasis: 24-week results from IXORA-S, a phase III study.

BACKGROUND: It has been shown that the interleukin (IL)-23/IL-17 axis is critical in the pathogenesis of psoriasis. OBJECTIVES: To present the primary end point (week 12) and safety and efficacy data up to week 24 from a head-to-head trial (IXORA-S) of the IL-17A inhibitor ixekizumab (IXE) vs. the IL-12/23 inhibitor ustekinumab (UST). METHODS: Randomized patients received IXE (160-mg starting dose, then 80 mg every 2 weeks for 12 weeks, then 80 mg every 4 weeks, n = 136) or UST (45 mg or 90 mg weight-based dosing per label, n = 166). The primary end point was the proportion of patients reaching ≥ 90% Psoriasis Area and Severity Index improvement (PASI 90). Hommel-adjusted key secondary end points at week 12 included PASI 75, PASI 100, static Physician's Global Assessment (sPGA) score of 0 or 1, sPGA score of 0, Dermatology Life Quality Index (DLQI) score of 0 or 1, ≥ 4-point reduction on the itch numerical rating scale (NRS) and changes in itch NRS and skin pain visual analogue scale. RESULTS: At week 12, IXE (n = 99, 72·8%) was superior to UST (n = 70, 42·2%) in PASI 90 response (response difference 32·1%, 97·5% confidence interval 19·8-44·5%, P < 0·001). Response rates for PASI 75, PASI 100 and sPGA (0,1) were significantly higher for IXE than for UST (adjusted P < 0·05). At week 24, IXE-treated patients had significantly higher response rates than UST-treated patients for PASI, sPGA and DLQI (unadjusted P < 0·05). No deaths were reported, and the treatments did not differ with regard to overall incidences of adverse events (P = 0·299). CONCLUSIONS: The superior efficacy of IXE demonstrated at week 12 persisted up to week 24. The safety profiles were consistent with those previously reported for both treatments.

Structure of bird communities in eucalyptus plantations: nestedness as a pattern of species distribution / Estrutura de comunidades de aves em plantios de eucalipto: aninhamento como padrão de distribuição de espécies

Abstract Replacement of native habitats by tree plantations has increased dramatically in Brazil, resulting in loss of structural components for birds, such as appropriate substrates for foraging and nesting. Tree plantations can also reduce faunal richness and change the composition of bird species. This study evaluated the structure of avian communities in eucalyptus plantations of different ages and in a native forest. We classified species as habitat specialists or generalists, and assessed if the species found in eucalyptus plantations are a subset of the species that occur in the native forest. Forty-one sampling sites were evaluated, with three point counts each, in a native forest and in eucalyptus plantations of four different ages. A total of 71 bird species were identified. Species richness and abundance were higher in the native forest, reflecting the greater heterogeneity of the habitat. The composition of bird species also differed between the native forest and plantations. The species recorded in the plantations represented a subset of the species of the native forest, with a predominance of generalist species. These species are more tolerant of habitat changes and are able to use the plantations. The commercial plantations studied here can serve as a main or occasional habitat for these generalists, especially for those that are semi-dependent on edge and forest. The bird species most affected by silviculture are those that are typical of open grasslands, and those that are highly dependent on well-preserved forests.

Resumo A substituição de ambientes nativos pela silvicultura está se tornando uma prática cada vez mais comum no Brasil, resultando na perda de componentes estruturais para as espécies de aves, como substratos específicos de forrageamento e nidificação. Esta prática pode reduzir a riqueza e alterar a composição das comunidades de aves. O objetivo deste estudo foi avaliar diferenças na estrutura de comunidades de aves em plantios de eucalipto de diferentes idades e em floresta nativa. Além disso, teve como objetivo classificar espécies em especialistas ou generalistas de habitat e avaliar se espécies encontradas nos plantios de eucalipto representam subconjuntos da floresta nativa. Quarenta e um sítios de amostragem foram avaliados, com três pontos de contagem cada, em uma floresta nativa e em plantios de eucalipto de quatro diferentes idades. Foi identificado um total de 71 espécies de aves. A riqueza de espécies e abundância foram maiores na floresta nativa refletindo a maior heterogeneidade desse habitat. A composição de espécies de aves também diferiu entre a floresta nativa e os plantios. As espécies registradas nos plantios representam um subconjunto das espécies da floresta nativa, o que é explicado pelo predomínio das espécies generalistas. Essas espécies são mais tolerantes às alterações de habitat e são capazes de utilizar os plantios. Nesse sentido, plantios comerciais estudados aqui podem servir como habitat para essas espécies seja de forma principal ou ocasional, especialmente para aquelas espécies de borda e semi-dependentes florestais. Por conseguinte, as espécies de aves mais prejudicadas pela silvicultura são espécies associadas à habitats campestres e aquelas que apresentam alta dependência a florestas bem preservadas.

Fish composition and species richness in eastern South American coastal lagoons: additional support for the freshwater ecoregions of the world.

The relationships between fish composition, connectivity and morphometry of 103 lagoons in nine freshwater ecoregions (FEOW) between 2·83° S and 37·64° S were evaluated in order to detect possible congruence between the gradient of species richness and similarities of assemblage composition. Most lagoons included in the study were <2 km(2) , with a maximum of 3975 km(2) in surface area. Combined surface area of all lagoons included in the study was 5411 km(2) . Number of species varied locally from one to 76. A multiple regression revealed that latitude, attributes of morphometry and connectivity, and sampling effort explained a large amount of variability in species richness. Lagoon area was a good predictor of species richness except in low latitude ecoregions, where lagoons are typically small-sized and not affected by marine immigrants, and where non-native fish species accounted for a significant portion of species richness. Relationships between species and area in small-sized lagoons (<2 km(2) ) is highly similar to the expected number in each ecoregion, with systems located between 18·27° S and 30·15° S attaining higher levels of species richness. Similarities in species composition within the primary, secondary and peripheral or marine divisions revealed strong continental biogeographic patterns only for species less tolerant or intolerant to salinity. Further support for the FEOW scheme in the eastern border of South America is therefore provided, and now includes ecotonal systems inhabited simultaneously by freshwater and marine species of fishes.

Structure of bird communities in eucalyptus plantations: nestedness as a pattern of species distribution.

Replacement of native habitats by tree plantations has increased dramatically in Brazil, resulting in loss of structural components for birds, such as appropriate substrates for foraging and nesting. Tree plantations can also reduce faunal richness and change the composition of bird species. This study evaluated the structure of avian communities in eucalyptus plantations of different ages and in a native forest. We classified species as habitat specialists or generalists, and assessed if the species found in eucalyptus plantations are a subset of the species that occur in the native forest. Forty-one sampling sites were evaluated, with three point counts each, in a native forest and in eucalyptus plantations of four different ages. A total of 71 bird species were identified. Species richness and abundance were higher in the native forest, reflecting the greater heterogeneity of the habitat. The composition of bird species also differed between the native forest and plantations. The species recorded in the plantations represented a subset of the species of the native forest, with a predominance of generalist species. These species are more tolerant of habitat changes and are able to use the plantations. The commercial plantations studied here can serve as a main or occasional habitat for these generalists, especially for those that are semi-dependent on edge and forest. The bird species most affected by silviculture are those that are typical of open grasslands, and those that are highly dependent on well-preserved forests.

Rare, low frequency and common coding variants in CHRNA5 and their contribution to nicotine dependence in European and African Americans.

The common nonsynonymous variant rs16969968 in the α5 nicotinic receptor subunit gene (CHRNA5) is the strongest genetic risk factor for nicotine dependence in European Americans and contributes to risk in African Americans. To comprehensively examine whether other CHRNA5 coding variation influences nicotine dependence risk, we performed targeted sequencing on 1582 nicotine-dependent cases (Fagerström Test for Nicotine Dependence score⩾4) and 1238 non-dependent controls, with independent replication of common and low frequency variants using 12 studies with exome chip data. Nicotine dependence was examined using logistic regression with individual common variants (minor allele frequency (MAF)⩾0.05), aggregate low frequency variants (0.05>MAF⩾0.005) and aggregate rare variants (MAF<0.005). Meta-analysis of primary results was performed with replication studies containing 12 174 heavy and 11 290 light smokers. Next-generation sequencing with 180 × coverage identified 24 nonsynonymous variants and 2 frameshift deletions in CHRNA5, including 9 novel variants in the 2820 subjects. Meta-analysis confirmed the risk effect of the only common variant (rs16969968, European ancestry: odds ratio (OR)=1.3, P=3.5 × 10(-11); African ancestry: OR=1.3, P=0.01) and demonstrated that three low frequency variants contributed an independent risk (aggregate term, European ancestry: OR=1.3, P=0.005; African ancestry: OR=1.4, P=0.0006). The remaining 22 rare coding variants were associated with increased risk of nicotine dependence in the European American primary sample (OR=12.9, P=0.01) and in the same risk direction in African Americans (OR=1.5, P=0.37). Our results indicate that common, low frequency and rare CHRNA5 coding variants are independently associated with nicotine dependence risk. These newly identified variants likely influence the risk for smoking-related diseases such as lung cancer.

Elicitation of health state utilities associated with varying severities of flares in Systemic Lupus Erythematosus.

BACKGROUND: Systemic Lupus Erythematosus (SLE) is characterised by fluctuating periods of minimal disease activity and 'flare'. Flare is an important outcome variable impacting the disease burden associated with SLE. The objective of this study was to obtain population-based utility values for varying severities of flare to measure the impact on health-related quality of life (HRQoL) in Australia, Canada, France, Japan, Spain and the UK. METHODS: Six health states (HS) for varying severities of flare were developed based on literature, patient blogs, and interviews with patients (n = 12), rheumatologists (n = 7) and nurses (n = 2). HS were validated by independent clinical experts (n = 6) and pilot interviews (n = 10, UK). HS were evaluated using the time-trade-off (TTO) method during face-to-face interviews with a minimum representative sample (n = 100) of the general population, per-country. Visual Analog Scale (VAS) scores were obtained to validate TTO scores. TTO scores were converted into utility values. RESULTS: The highest mean TTO utility scores were observed for the anchor HS (minimal disease activity) across all countries; means ranged from 0.66 in Japan to 0.82 in UK. All flare HS were associated with a disutility compared with the anchor HS (p < 0.001), means ranged across countries: mild flare HS: 0.55-0.71, moderate flare HS: 0.38-0.53, severe renal flare HS: 0.33-0.45, severe central nervous system (CNS) flare HS: 0.30-0.45 and severe generalised flare HS: 0.19-0.33. Mean VAS scores followed the same trend. CONCLUSIONS: These results show increasing severity of flare has a detrimental impact on HRQoL. The severe generalised flare HS received the lowest mean utility score suggesting that the perceived day-to-day impact of a severe generalised flare was greater than a severe CNS or severe renal flare. This is, to the best of our knowledge, the first utility study to assess varying severities of flare in SLE across six different countries.

Smoking cessation is associated with lower rates of mood/anxiety and alcohol use disorders.

BACKGROUND: The psychological outcomes that accompany smoking cessation are not yet conclusive but positive outcomes could help to persuade quitting. METHOD: We used data from the longitudinal National Epidemiological Study of Alcohol and Related Conditions. Logistic regression was used to examine associations between cigarette smoking reduction and Wave 2 status of addiction/mental health disorder among daily smokers at Wave 1, stratified by status of the diagnosis of interest at Wave 1. We adjusted for differences in baseline covariates between smokers with different levels of smoking reduction between Wave 1 and Wave 2 using propensity score regression adjustment. RESULTS: After adjusting for propensity scores and other mental health/addiction co-morbidities at Wave 2, among daily smokers who had current or lifetime history diagnosis of the outcome of interest at Wave 1, quitting by Wave 2 predicted a decreased risk of mood/anxiety disorder [adjusted odds ratio (aOR) 0.6, 95% confidence interval (CI) 0.4-0.9] and alcohol disorder (aOR 0.7, 95% CI 0.5-0.99) at Wave 2. Among daily smokers with no lifetime history diagnosis of the outcome of interest at Wave 1, quitting smoking by Wave 2 predicted a decreased risk of drug use disorder at Wave 2 (aOR 0.3, 95% CI 0.1-0.9). CONCLUSIONS: There is no support in our data for the concern that smoking cessation would result in smokers' increased risk of some mental disorders. To the contrary, our data suggest that smoking cessation is associated with risk reduction for mood/anxiety or alcohol use disorder, even among smokers who have had a pre-existing disorder.

Noncontrast CT in deep cerebral venous thrombosis and sinus thrombosis: comparison of its diagnostic value for both entities.

BACKGROUND AND PURPOSE: With its highly variable clinical presentation, the diagnosis of cerebral venous sinus thrombosis (SVT), and especially of deep venous thrombosis (DVT), as rare but important causes of stroke is challenging. Because noncontrast cranial CT (NCCT) is still the imaging technique of choice in most emergency departments, we aimed to investigate its value in the diagnosis of SVT and DVT. MATERIALS AND METHODS: Screening our patient data base, we identified 8 patients with DVT and 25 patients with SVT. We also included a control group of 36 patients who had presented with clinical signs of DVT or SVT but in whom thrombosis was subsequently excluded. MR imaging, multidetector row CT angiography (MDCTA), and/or digital subtraction angiography (DSA) were used as the reference standard. Three independent readers assessed the NCCTs for the presence of direct and indirect signs of DVT or SVT. Direct signs included the presence of hyperattenuated sinuses (ie, cord sign) or veins (ie, attenuated vein sign), whereas parenchymal edema and hemorrhage were indirect signs. RESULTS: The sensitivity and specificity of the attenuated vein sign for the diagnosis of DVT were 100%, and 99.4%, respectively, whereas the sensitivity and specificity of the cord sign for SVT were 64.6% and 97.2%, respectively. The sensitivity and specificity values of NCCT were 93.7% and 98% for intracerebral edema and 94.8% and 98.7% for intracerebral hemorrhages, respectively. CONCLUSIONS: Although NCCT is insufficient to exclude a SVT, its value in the emergency diagnosis of DVT seems to be very high.

Feeding dynamics and ecomorphology of Oligosarcus jenynsii (Gunther, 1864) and Oligosarcus robustus (Menezes, 1969) in the Lagoa Fortaleza, southern Brazil.

Oligosarcus jenynsii and Oligosarcus robustus are fishes of Characidae family that occur in Rio Grande do Sul, Uruguay and northern Argentina. This work purported to study the feeding dynamics (repletion and hepatosomatic indexes and condition factor) over time, and to investigate the coexistence of these two species by evaluating the partition of resources using qualitative and quantitative analyses of diet, temporal and spatial segregation throughout the water column and some ecomorphological aspects of the species in the Lagoa Fortaleza. Specimens were sampled monthly, from May 2000 to April 2001 during 24 h/month, using stationary gill nets of different mesh sizes. The records of each individual included total and standard length; total, stomach and liver weight; sex and stomach repletion. The variation of the mean values of repletion index and relative frequencies of stomach repletion stages indicate that O. jenynsii and O. robustus do not present seasonal differences in feeding intensity. The hepatosomatic index shows an allocation of energy to the liver during every period except reproduction, when part of the energy is used for gonad maturation. The estimated condition factor for both species reveals an increase in the reproductive period, evidencing the influence of gonads upon the condition of the fish. The diet analysis revealed that O. robustus is piscivorous, whereas O. jenynsii is a generalist carnivore, tending to piscivory as well. The active period of O. robustus is more concentrated at sunrise and sunset, whereas O. jenynsii is continually active, a characteristic related to hunting for prey. The ecomorphological analysis revealed differences between the two species in the dimensions of the mouth. Evidence suggests that the species coexist, sharing food sources, differing in oral morphology but ingesting similar prey, possibly because food is not a limiting factor in the environment.

Feeding dynamics and ecomorphology of Oligosarcus jenynsii (Gunther, 1864) and Oligosarcus robustus (Menezes, 1969) in the Lagoa Fortaleza, southern Brazil

Oligosarcus jenynsii e Oligosarcus robustus são peixes pertencentes à família Characidae, sendo espécies ocorrentes no Rio Grande do Sul, Uruguai e norte da Argentina. Este estudo objetivou analisar os índices de repleção e hepatossomático e o fator de condição ao longo do tempo, fazer uma análise quali-quantitativa da dieta, e avaliar a segregação temporal e espacial ao longo da coluna d água e ecomorfologia, como parâmetros de coexistência entre estas duas espécies. Os exemplares foram amostrados mensalmente, de maio de 2000 a abril de 2001, durante 24 horas/mês, com o auxílio de redes de espera de diversas malhagens. De cada indivíduo foram registradas medidas de comprimento total e padrão, peso total, peso do estômago e do fígado, sexo e estádio de repleção estomacal. Os resultados demonstram que O. jenynsii e O. robustus não apresentam um período alimentar definido, alimentando-se durante todo o tempo conforme a variação dos valores médios do índice de repleção, bem como das freqüências relativas dos estádios de repleção estomacal. O índice hepatossomático demonstra uma alocação de energia para o fígado durante todo o período, exceto na época reprodutiva, quando a energia é transferida para a maturação gonadal. O fator de condição estimado para as duas espécies revelou um aumento na época reprodutiva, evidenciando a influência das gônadas na condição em que se encontra o peixe. As análises na dieta revelaram que O. robustus é piscívoro, enquanto O. jenynsii se mostrou um carnívoro mais generalista, tendendo à piscivoria. O período de atividade das espécies foi crepuscular e está diretamente relacionado com a captura de presas. As análises ecomorfológicas revelaram diferenças no tamanho da cabeça e dimensões da boca entre as espécies. Os resultados obtidos sugerem que as espécies coexistem partilhando o recurso alimentar, diferindo em sua morfologia bucal, ingerindo, no entanto, presas similares porque o alimento pode não ser um fator limitante no ambiente.

Feeding dynamics and ecomorphology of Oligosarcus jenynsii (Gunther, 1864) and Oligosarcus robustus (Menezes, 1969) in the Lagoa Fortaleza, southern Brazil

Oligosarcus jenynsii and Oligosarcus robustus are fishes of Characidae family that occur in Rio Grande do Sul, Uruguay and northern Argentina. This work purported to study the feeding dynamics (repletion and hepatosomatic indexes and condition factor) over time, and to investigate the coexistence of these two species by evaluating the partition of resources using qualitative and quantitative analyses of diet, temporal and spatial segregation throughout the water column and some ecomorphological aspects of the species in the Lagoa Fortaleza. Specimens were sampled monthly, from May 2000 to April 2001 during 24 h/month, using stationary gill nets of different mesh sizes. The records of each individual included total and standard length; total, stomach and liver weight; sex and stomach repletion. The variation of the mean values of repletion index and relative frequencies of stomach repletion stages indicate that O. jenynsii and O. robustus do not present seasonal differences in feeding intensity. The hepatosomatic index shows an allocation of energy to the liver during every period except reproduction, when part of the energy is used for gonad maturation. The estimated condition factor for both species reveals an increase in the reproductive period, evidencing the influence of gonads upon the condition of the fish. The diet analysis revealed that O. robustus is piscivorous, whereas O. jenynsii is a generalist carnivore, tending to piscivory as well. The active period of O. robustus is more concentrated at sunrise and sunset, whereas O. jenynsii is continually active, a characteristic related to hunting for prey. The ecomorphological analysis revealed differences between the two species in the dimensions of the mouth. Evidence suggests that the species coexist, sharing food sources, differing in oral morphology but ingesting similar prey, possibly because food is not a limiting factor in the environment.

Oligosarcus jenynsii e Oligosarcus robustus são peixes pertencentes à família Characidae, sendo espécies ocorrentes no Rio Grande do Sul, Uruguai e norte da Argentina. Este estudo objetivou analisar os índices de repleção e hepatossomático e o fator de condição ao longo do tempo, fazer uma análise quali-quantitativa da dieta, e avaliar a segregação temporal e espacial ao longo da coluna d´água e ecomorfologia, como parâmetros de coexistência entre estas duas espécies. Os exemplares foram amostrados mensalmente, de maio de 2000 a abril de 2001, durante 24 horas/mês, com o auxílio de redes de espera de diversas malhagens. De cada indivíduo foram registradas medidas de comprimento total e padrão, peso total, peso do estômago e do fígado, sexo e estádio de repleção estomacal. Os resultados demonstram que O. jenynsii e O. robustus não apresentam um período alimentar definido, alimentando-se durante todo o tempo conforme a variação dos valores médios do índice de repleção, bem como das freqüências relativas dos estádios de repleção estomacal. O índice hepatossomático demonstra uma alocação de energia para o fígado durante todo o período, exceto na época reprodutiva, quando a energia é transferida para a maturação gonadal. O fator de condição estimado para as duas espécies revelou um aumento na época reprodutiva, evidenciando a influência das gônadas na condição em que se encontra o peixe. As análises na dieta revelaram que O. robustus é piscívoro, enquanto O. jenynsii se mostrou um carnívoro mais generalista, tendendo à piscivoria. O período de atividade das espécies foi crepuscular e está diretamente relacionado com a captura de presas. As análises ecomorfológicas revelaram diferenças no tamanho da cabeça e dimensões da boca entre as espécies. Os resultados obtidos sugerem que as espécies coexistem partilhando o recurso alimentar, diferindo em sua morfologia bucal, ingerindo, no entanto, presas similares porque o alimento pode não ser um fator limitante no ambiente.

Mortality study of 18 000 patients treated with omeprazole.

BACKGROUND: The long term safety of potent gastric acid suppressive therapy has yet to be established. METHOD: General practice record review at a median interval of 26 months followed by retrieval of details of all deaths within four years using the UK National Health Service Central Registers in 17 936 patients prescribed omeprazole in 1993-1995. Death rates were compared with general population rates. RESULTS: Records of 17 489 patients (97.5%) were examined. A total of 12 703 patients received further scripts for antisecretory drugs, 8097 for omeprazole only (65.6%): 3097 patients have died. All cause mortality was higher in the first year (observed/expected (O/E) 1.44 (95% confidence intervals (CI) 1.34-1.55); p<0.0001) but had fallen to population expectation by the fourth year. There were significant mortality increases in the first year, falling to or below population expectation by the fourth year, for deaths ascribed to neoplasms (1.82 (95% CI 1.58-2.08); p<0.0001), circulatory diseases (1.27 (95% CI 1.13-1.43); p<0.0001), and respiratory diseases (1.37 (95% CI 1.12-1.64); p<0.001). Increased mortality ascribed to digestive diseases (2.56 (95% CI 1.87-3.43); p<0.0001) persisted, although reduced. Increased mortality rates for cancers of the stomach (4.06 (95% CI 2.60-6.04); p<0.0001), colon and rectum (1.40 (95% CI 0.84-2.18); p=0.075), and trachea, bronchus, and lung (1.64 (95% CI 1.19-2.19); p<0.01) seen in the first year had disappeared by the fourth year but that for cancer of the oesophagus had not (O/E 7.35 (95% CI 5.20-10.09) (p<0.0001) in year 1; 2.88 (95% CI 1.62-4.79) (p<0.001) in year 4). Forty of 78 patients dying of oesophageal cancer had the disease present at registration. Twenty seven of those remaining cases had clinical evidence of Barrett's disease, stricture, ulcer, or oesophagitis at registration (O/E 3.30 (95% CI 2.17-4.80)). Six deaths occurred in patients with hiatal hernia or reflux only (O/E 1.02 (95% CI 0.37-2.22)) and five in patients without oesophageal disease (O/E 0.77 (95% CI 0.25-1.80)). No relationships were detected with numbers of omeprazole scripts received. CONCLUSIONS: Increases in mortality associated with treatment are due to pre- existing illness, including pre-existing severe oesophageal disease. There was no evidence of an increased risk of oesophageal adenocarcinoma in those without oesophageal mucosal damage recorded at registration.

Leukocyte apoptosis in whole blood involves platelet-dependent coaggregation.

BACKGROUND: Activated leukocytes and platelet-leukocyte interaction are involved in the pathogenesis of thrombotic and inflammatory events. Because apoptosis is a prerequisite for the successful resolution of an inflammatory response, we investigated the amount of apoptotic peripheral blood leukocytes (PBLs) in whole blood and their possible functional relation with the platelet-leukocyte interaction by a flow cytometric assay using APO 2.7 antibody for the detection of apoptosis METHODS: Thirty healthy subjects volunteered for the study. PBL apoptosis in seven volunteers was induced by phorbol 12-myristate 13-acetate or while standing at rest. RESULTS: Apoptosis was observed in all types of leukocytes (0.7% neutrophils, 1.5% monocytes, and 0.3% lymphocytes). Apoptosis was found predominantly in platelet and leukocyte coaggregates (<1% of nonaggregated leukocytes vs. 9% of platelet and leukocyte coaggregates). This phenomenon was even more pronounced after induction of leukocyte apoptosis in vitro (66% of platelet and leukocyte coaggregates). CONCLUSIONS: Apoptosis and platelet-leukocyte interaction seemed to be closely related phenomena, and apoptotic leukocytes seemed to trigger adhesion and, hence, activation of platelets. Because platelet-leukocyte interaction is involved in the pathogenesis of thrombotic events, apoptotic leukocytes may constitute an additional prothrombotic trigger.

Physicians' knowledge, attitudes, and practice of pharmacologic treatment of hypertension.

OBJECTIVE: To explore how well physicians who treat hypertension know the indications and contraindications for particular antihypertensive therapies, and how closely their opinions and practice of hypertension treatment agree with national guidelines. METHODS: We surveyed by mail a stratified random sample of 10,000 US cardiologists, internists, and general/family practitioners. This survey explored their knowledge, attitudes, and practices with respect to the treatment of hypertension. Responses were compared with national guidelines and product labeling at the time of the survey. Results were stratified by physician specialty. RESULTS: A total of 1,023 physicians, or 10.2% of the sample, responded to the survey. Only 37.3% answered all four knowledge questions correctly, including 25.7% of general/family practitioners, 38.3% of internists, and 49.5% of cardiologists (p < 0.001). In their attitudes with respect to evaluating high blood pressure and establishing treatment goals, most respondents agreed with established guidelines. However, when asked how they would treat uncomplicated, mild hypertension, only 23% limited their selection to diuretics and beta-blockers in accordance with the guidelines. Cardiologists in particular were more likely than internists or general/family practitioners to choose other drug classes, such as angiotensin-converting enzyme Inhibitors or calcium-channel blockers. CONCLUSIONS: The results of our survey suggest that national efforts to educate physicians about the increasingly complex armamentarium for hypertension, and to persuade them to base their prescribing on the results of randomized, controlled trials of primary prevention, must be continued.

Interference in the Limulus amebocyte lysate assay for endotoxin determination in peritoneal dialysis fluids and concentrates for hemodialysis.

The interference of the saline concentration of fluids for peritoneal dialysis and concentrates for hemodialysis on the Limulus amebocyte lysate (LAL) assay for endotoxins was investigated. The experiments were carried out individually with each substance that compose fluids for hemodialysis, to determine the possible inhibition or enhancement effects that they could cause on the LAL assay. The compositions were also assayed to investigate the possibility of synergistic effect. They were assayed by the gel-clot method from two different suppliers, and the samples that showed inhibition effect were also assayed by the chromogenic method. The samples were analysed at successive dilutions, with different LAL sensitivities, to satisfy the endotoxin limits of 5 EU/ml for the concentrate and 0.25 EU/ml for the fluid for dialysis peritoneal. The results showed that the major interference on the gel-clot assay occurs in presence of acetic acid and in concentrates containing acid acetic, even the pH being adjusted between 6.5 and 7.5. However, the test, after an adequate dilution, could be validating for all samples. Chromogenic test can be used for peritoneal dialysis fluids considering a limit of 0.25 EU/ml and sample dilution of eight times, but it cannot be used for concentrates for hemodialysis without further dilution. Considering the results and that the chromogenic is a more time-consuming method, endotoxins in fluids for hemodialysis can be satisfactorily assayed by the gel-clot method.