6%) as Child-Pugh B and only one (2 4%) patient was classified as

6%) as Child-Pugh B and only one (2.4%) patient was classified as Child-Pugh A. Three patients (7.1%) were previously diagnosed with SBP, but only one of them (2.4%) was on antibiotic prophylaxis at admission. Seventeen patients (40.5%) did EPZ-6438 chemical structure not have esophageal varices, and 25 (59.5%) had varices (8 [19%] with hemorrhage and 17 [40.5%] without). At hospital admission 12 patients (28.6%) were on proton pump inhibitors, 25 (59.5%) had total serum bilirubin ≥2.5 mg/dL, 21 (50%) had plasma creatinine ≥1.2 mg/dL and 13 (31%) had plasma sodium ≤130 mEq/L (see Table 2). Total serum bilirubin, plasma creatinine, plasma sodium and the presence of esophageal varices did not show a statistically significant association with a higher

mortality Seliciclib risk. Regarding the first paracentesis done during hospitalization, 71.4% (n = 30) of the ascitic fluids analyzed were culture-negative and 4.8% (n = 2), despite having cytochemical SBP criteria, were not submitted to bacteriological testing. Escherichia coli (n = 7; 16.7%) was the pathogen most frequently isolated, with Citrobacter freundii, Listeria monocytogenis and Streptococcus salivarius being isolated once each (see Table 3). Twenty three (54.8%) patients had ascitic fluid total protein concentration

<1.5 g/dL at admission; survival in these patients, however, was not statistically different from those with higher protein concentration (p = 0.612; log rank test). Thirty one (73.8%) patients were treated with Ceftriaxone, three (7.14%) with Ciprofloxacin, one (2.38%) with Piperacilin/Tazobactam and one (2.38%) with Levofloxacin; there was no information regarding the antibiotic regimen used in the clinical records of six (14.28%) patients. Of those on Ceftriaxone, 10 (32.25%) did not respond to the treatment and were switched to another antibiotic (see Table 4). Of the 21 (50%) patients who repeated paracentesis during hospitalization, 19 (45.2%) had culture-negative ascitic fluid, one (2.4%) was positive for Escherichia coli and one (2.4%) for Enterococcus faecalis plus Aeromonas hydophila. The average length of

hospitalization was 16.10 ± 12.01 days, with men having a longer length stay (17.21 ± 12.65 Interleukin-2 receptor days) than women (11.38 ± 7.70 days). Yet, this difference was not statistically significant (p = 0.221). Regarding complications (see Table 5) registered during hospitalization, the presence of renal failure (RF) was associated with a higher mortality risk (OR = 8.1; p = 0.005; chi-square test), which is re-enforced by using the Cox regression (HR = 3.25; p = 0.063), suggesting a 3 times higher risk of death in these patients; there is statistical significance (p = 0.045; log rank test) when comparing the survival curves regarding the presence or absence of RF (see Fig. 1). The presence of septic shock was also associated with a higher mortality risk (OR = 54; p < 0.001; chi-square test), with a 9 times higher risk of death (HR = 9.5; p = 0.

Detailed knowledge of the molecular mechanisms underlying ubiquit

Detailed knowledge of the molecular mechanisms underlying ubiquitin processing provided an inroad for designing molecular

probes targeting conjugating and deconjugating enzymes. This approach has regained interest also because it allows small molecule inhibitor development within the UPS [42]. Whereas ubiquitin processing enzymes (USPs, UCHs, OTUs) can be readily profiled using ubiquitin based chemical probes targeting proteolytic catalysis, the application of this activity-based approach towards the ubiquitin conjugating see more cascade has proven to be challenging [43 and 44], although chemical crosslinking was successfully used for HECT domain E3 ligases [45]. In the case of deubiquitination, further progress has been made to create molecular probes mimicking different isopeptide linkages between ubiquitin and protein substrates including ubiquitin itself by integrating peptides at the P′ side of the scissile bond with an electrophilic moiety in the center, which appear to selectively target subsets of DUBs in crude cell extracts [46]. This approach will complement predominantly in vitro studies on how DUBs can distinguish between different poly-ubiquitin chains for processing, currently achieved using model substrates [47] or fluorescence resonance techniques [48]. Also, more recent

probes on the basis of the ubiquitin scaffold are now available with Pirfenidone cell line C-terminal Silibinin fluorescent moieties via ‘Click Chemistry’ [49], or N-terminal fluorescent or photoreactive moieties through total synthesis [50 and 51•]. Such tools will undoubtedly be used to profile ubiquitin processing enzymes such as DUBs, but also related enzymes specifically recognizing ubiquitin-like proteins, and thereby contribute to our understanding the role of these enzymes within the ubiquitin network in normal physiology as well as disease pathogenesis (Figure 4). The author declares no conflict of interest

in relation to the work described in this manuscript. Papers of particular interest, published within the period of review, have been highlighted as: • of special interest I am grateful for all the helpful discussions with colleagues and would like to apologise for all references that were not cited because of space constrains. “
“Current Opinion in Chemical Biology 2013, 17:73–82 This review comes from a themed issue on Omics Edited by Matthew Bogyo and Pauline M Rudd For a complete overview see the Issue and the Editorial Available online 6th January 2013 1367-5931/$ – see front matter, © 2013 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.cbpa.2012.11.025 Proteomics has made astonishing advances in all areas including peptide enrichment, fractionation, mass spectrometry and data analysis — many of which are reviewed in this issue.

Além disso, a nossa amostra é pequena e algo heterogénea, ao incl

Além disso, a nossa amostra é pequena e algo heterogénea, ao incluir doentes com CU e com DC e, neste último caso, com 34,3% de doentes com remissão induzida através de cirurgia. Contudo, estes aspetos não nos parecem ser limitações major do nosso estudo, pois a eficácia das tiopurinas foi semelhante em ambos os grupos e concordante com a encontrada no estudo de Constantino 11 (69% na CU e 66,7% na DC). Na nossa série a taxa de efeitos secundários foi de 30,6%, a maioria ocorrendo nos primeiros 3 meses de tratamento. Todos os efeitos

secundários levaram à descontinuação da terapêutica; estes valores são concordantes com outros estudos12, 22 and 23. No nosso estudo, o sexo e o tipo de doença não apresentaram relação com a eficácia da AZA a longo prazo. No que respeita ao tipo click here de doença, os nossos dados são concordantes com uma série do Hospital John Radcliffe,

em Oxford22, que visou a avaliação retrospetiva da utilização da AZA durante 30 anos. Neste estudo, a CU foi um fator favorecedor para a obtenção da remissão, mas não se verificou diferença entre DC e CU na manutenção da remissão. O mesmo é referido no estudo de Constantino11 onde, e de forma semelhante à nossa série, não se observou relação entre o tipo de doença e a eficácia a longo prazo da AZA. Já no que respeita ao sexo encontram‐se dados algo contraditórios na literatura: no estudo de Oxford22 os doentes do sexo masculino com DC foram os que tiveram maior probabilidade Selleck ERK inhibitor de se manterem em remissão a longo prazo sob terapêutica com AZA; pelo contrário, no estudo italiano supracitado11 e num outro estudo asiático24, o sexo feminino esteve associado positivamente à resposta à terapêutica. Subdividindo os doentes de

acordo com o tipo de doença, também não verificamos diferença na resposta de acordo com o fenótipo, localização e presença de doença perianal na DC; os nossos Molecular motor dados são concordantes com um estudo prévio francês25, que visou estudar 157 doentes com DC em remissão por mais de 6 meses e em que o local de envolvimento da doença não apresentou relação com a resposta à AZA; já no estudo de Costantino11, nos doentes com DC, observou‐se resposta significativamente mais favorável quando a localização era ileal. Por fim, na nossa série, verificou‐se que os doentes com colite esquerda apresentam significativamente melhor resposta sustentada à AZA, contrariamente ao estudo de Costantino11 e a um outro estudo espanhol de Lopez‐Sanroman21. Já Saibeni26 mostrou que a eficácia das tiopurinas seria independente da localização da doença, independentemente de se tratar de CU ou DC. Os PL antes do início da AZA não predizem a resposta à terapêutica, pelo que os valores das análises, antes de iniciar a AZA, não são úteis como preditores de resposta a longo prazo a este fármaco.

CSF is mainly produced at the choroid plexus, where it is separat

CSF is mainly produced at the choroid plexus, where it is separated by blood circulation through the blood–CSF barrier. DNA Damage inhibitor It is produced at a flow-rate of approximately 500 mL/24 h [80] and its composition is strictly regulated by the selectivity of the BBB [79]. The CSF proteome is

for its most part (80%) composed of proteins derived from blood and, as in plasma, albumin and immunoglobulins represent approximately 70% of the total amount of CSF protein [81]. The remaining 20% of CSF proteins are produced in the brain, although they are rarely considered brain specific [80] and [82]. Since late stage HAT is characterized by a meningo-encephalitis [14] and [83] and that CSF examination is part of the current diagnostic workflow, the reasoning for looking for novel disease progression markers in this body fluid seems pertinent. Alterations in the protein content of CSF are of particular clinical utility for Alectinib order many neurological disorders. An increased protein concentration can be indicative of either a BBB dysfunction or an increased intrathecal synthesis of proteins.

The quotients of albumin (QAlb) and immunoglobulin (QIg) are used to evaluate and quantify this dysfunction [79], [80] and [82], and the latter can be particularly helpful to indicate an inflammatory process occurring in the brain [82] and [84]. The increased concentration of immunoglobulins in the CSF of late stage HAT patients, with IgM being the predominant class, has been known since the 1980s [85]. This observation agrees with the absence of the switch between IgM and IgG, and the low decay of CSF antibodies characteristic of

the humoral immune response in the brain [82]. More recently, it has been demonstrated that an increased fraction of IgM of intrathecal origin in S2 HAT patients [73] and [86] is indicative of the presence of a brain inflammatory Org 27569 process not associated to damage of the BBB. IgM, and in particular those of intrathecal origin, are currently considered as the best alternative to a WBC count for staging T. b. gambiense HAT. A rapid agglutination test for the evaluation of IgM concentration in CSF has been developed (Latex/IgM) and a high correlation between the final Latex/IgM titer and intrathecal IgM production has been shown [87] and [88]. Despite this method has high accuracy for stage determination [88], strong enough evidence to support its introduction into clinical practice is still missing. Moreover, Latex/IgM exhibited limited utility for the evaluation of outcomes after treatment. Indeed, Latex/IgM combined with a WBC count accurately detected relapses at 18 months after treatment, but IgM normalized very slowly over time in cured patients [89] and [90].

It also is worth noting that although the relative risk was 40% h

It also is worth noting that although the relative risk was 40% higher in women with diagnosed CD, the absolute excess risk was calculated to be only 0.5%. The overall rate of new clinically recorded fertility problems in women with symptomatic CD was found to be slightly lower than the rates in women without CD. These lower rates may be explained by an increased focus on resolving celiac symptoms before women try to conceive or the lack of more specific metrics of disease severity in our data. The current evidence regarding CD in small groups of women with unexplained infertility from a small number of studies has been generalized to raise

concern among all women with CD by highlighting women with infertility as one of the associated conditions Panobinostat mouse in CD.17, 45 and 46 Although undiagnosed CD is likely to be an underlying cause of unexplained infertility for some women, our findings indicate that most women with celiac disease, either undiagnosed or diagnosed, do not have a substantially

greater likelihood of clinically Selleck Docetaxel recorded fertility problems than women without CD. Therefore, screening when women initially present with fertility problems may not identify a significant number of women with CD, beyond the general population prevalence. This may not always apply to subgroups of women with severe celiac disease. However, in terms of the clinical burden of fertility problems at a population level, these findings should be reassuring for women with CD and all stakeholders involved in

their care. “
“Infliximab is a recombinant chimeric IgG-1κ monoclonal antibody that neutralizes the biologic activity of tumor necrosis factor (TNF)-α. Infliximab is approved for the treatment of patients with moderate-to-severe ulcerative colitis (UC) based on the results of SPTLC1 the Active Ulcerative Colitis Trials 1 and 2 (ACT-1 and ACT-2), which evaluated 728 patients with moderate-to-severe disease. In these studies, patients treated with infliximab at weeks 0, 2, and 6 and every 8 weeks thereafter were more likely to show clinical response, clinical remission, and mucosal healing at weeks 8, 30, and 54 than patients assigned to placebo.1 and 2 Previous pharmacokinetic (PK) evaluations of infliximab use in patients with UC have shown a linear relationship between dose and serum infliximab concentration,3 and that the systemic disposition of infliximab is influenced by body weight, serum albumin level, and the formation of antibodies to infliximab (ATI).4 In addition, serum infliximab concentrations have been found to influence the response to treatment in Crohn’s disease,5 and 6 rheumatoid arthritis,7 and psoriasis.8 Therapeutic drug monitoring potentially can improve outcomes in patients receiving TNF antagonists, particularly in those who have lost response to these agents owing to inadequate serum drug concentrations.

After the eye had passed over the mouth of the Bay (17 September)

After the eye had passed over the mouth of the Bay (17 September), the flow direction changed to seaward along the entire cross-section in the lower Bay and mainly two-layered circulation in the deep portion of the Bay. The salinity decreased by approximately 3–4 ppt. On the next day (18 September), a landward return flow occurred throughout the entire transect (Fig. 12(a)). Stratification in the deep channel was increased by 3–4 ppt due to a relatively strong saltier water inflow through the bottom layer. Within a week, the non-tidal flow across the cross-section http://www.selleckchem.com/products/i-bet-762.html appeared to

return to a two-layered circulation pattern, and the vertical salinity structure appeared to be adjusted by the restratification process (not shown). Veliparib purchase During Hurricane Isabel, prior to the passage of the strongest wind, the salinity difference between surface and bottom waters in the deep channel was approximately 6–7 ppt, which is 4–5 ppt greater than the

pre-Floyd condition. On 18 September, with the northeasterly wind on the continental shelf, we see that vertically homogeneous saltwater was pumping into the Bay from the ocean (Fig. 12(b)). The mid- and upper Bay portions also have strong components of landward bottom flow. On 19 September, when the hurricane passed by, a strong band of surface landward flow showed in the mid- and upper Bay portions and the previously stratified water became relatively well-mixed. On 20 September, the

very strong seaward flow rebounded, and the SPTLC1 stratification in the vertical water column of the Bay started to increase by 2, 1.5, and 5 ppt in the upper, middle, and the lower Bay, respectively (Fig. 12(b)). Within about a week, the net flow appears to return to a two-layered circulation pattern with a 7–8 ppt salinity difference between surface and bottom waters in the channel (not shown). A comparison of the Bay’s response to the two hurricanes features a few highlights: (1) Prior to the storms, there was a significant difference between the observed stratification (ΔS) in the Bay (Table 5). At CB4.4, pre-Floyd stratification was nearly 4 ppt whereas pre-Isabel stratification was nearly 11.5 ppt. (2) In the lower Bay, it is clear that the saltwater intrusion occurred during both hurricanes. (3) Overall, the winds during both hurricanes generated vertical mixing that destratified the water column. Even during the peak of the hurricane events, however, the deep portion of the mid-Bay remained stratified. Following Lerczak et al. (2006), the total salt flux is expressed by: equation(7b) Fs=〈∬usdA〉Fs=∬usdAwhere the angle bracket denotes a 33-h low-pass filter, u is the axial velocity, s is salinity, and the cross-sectional integral within the angle bracket represents the instantaneous salt flux.

Surface salinity was calculated as monthly means using data obtai

Surface salinity was calculated as monthly means using data obtained from the National Oceanographic Data Center. Surface temperature was calculated using the European Centre for Medium-Range Weather Forecasts database with a 6-h temporal resolution. The Etoposide ic50 monthly average southern Tyrrhenian surface temperature and salinity were 13.4–28.5 ° C and 37.15–38.07 PSU respectively over the study period. Equation (5) was applied in calculating daily Qin values from May 2006 to June 2009 using the AVISO satellite database. These values were then used

for the whole period studied; although this represents an approximation, it is supported as tides are mainly short-term and periodic and the differences between the monthly average values of surface temperature Hormones antagonist and salinity for the eastern and western sides of the Sicily Channel are small. In future work, the Mediterranean climate system will be modelled using a large number of coupled sub-basin models, with the Sicily Channel flow being treated as a baroclinic exchange flow. The sensitivity

of the assumption will be further analysed by running several sensitivity experiments (see section 3.2). Bathymetric information and the area-depth distribution of the studied basin are depicted in Figure 1 and Figure 2. The surface area is 1.67 × 1012 m2, the water volume 2.4 × 1015 m3, the average depth 1430 m and the maximum depth 5097 m. The annual average freshwater runoff was 12 943 m3 s− 1, and the average precipitation and evaporation were 1.58 and 3.76 mm day− 1 respectively. Moreover, the average monthly surface salinity and water temperature over the entire basin ranged from 38.3 to 38.8 PSU and 14.8 to 27 ° C respectively. The cross-sectional area of the Sicily Channel

was calculated from bathymetric data (Figure 2b). Figure 2b shows that the Channel width from the southern to the northern parts is approximately 149 km and that the southern part is deeper than the northern part. The maximum depth across the Channel is 830 m. Satellite data on the sea level across the Sicily Channel were used to calculate the surface current flow from the western to eastern basins using equation (5). Figure 3 depicts some examples from these calculations of how the surface currents can take various routes. These routes must be considered when measuring nearly or calculating the Channel exchange. To resolve the mesoscale currents passing through the channel, the area was divided into 17 grid cells from which the Qin values were calculated. The temporal variations in the surface- and deep-layer flows are shown in Figure 4. The calculated surface flows over the period (early June 2006-late June 2009) ranged from 0.25 to 2.56 × 106 m3 s− 1, averaging 1.16 ± 0.34 × 106 m3 s− 1, while the deep flows were in the same range but with a slightly lower averaged value of 1.13 ± 0.36 × 106 m3 s− 1, indicating a loss of water in the EMB due to evaporation.

The result of the present study clearly showed that the levels of

The result of the present study clearly showed that the levels of SOD and catalase are remarkably decreased in rats treated with lead acetate. Lead acetate is known to cause free radical damage in tissues by two mechanisms: Increased generation of ROS, including hydroperoxides, singlet oxygen and hydrogen peroxides, and by Doxorubicin cost causing direct depletion of antioxidant reserves [20] and [21]. The observed decrease in circulating antioxidants and decrease in serum total antioxidants confirm the lead acetate-induced depletion of antioxidants [22]. All antioxidant enzymes including SOD and catalase decreased significantly in mitochondrial and post-mitochondrial

fraction of testis of lead and cadmium treated rats [19]. There is a significant

decrease in the activity levels of antioxidant enzymes superoxide dismutase and catalase in the testes of lead exposed rats [23]. In the present study, when the cinnamon and lead acetate was administrated to rats, the level of SOD was increased compared to its level in rats treated only with lead. The activities of liver SOD and catalase was significantly reduced in the carbon tetrachloride intoxicated group, while it was significantly elevated in the groups pretreated with either water or ethanol extracts of cinnamon find more [24]. Generally the effects of cinnamon have not yet been fully identified on reproductive system. This study concentrated on the effect of cinnamon extract on several reproductive parameters after lead exposure and its ability to correct the adverse effect of lead on seminal picture and testicular structure in rats. The improvement of reproductive parameters after cinnamon administration should be explained. One of the possible explanations is that concentration

of LH, FSH and testosterone hormones have been increased significantly after cinnamon administration [25]. This effect could be due to the presence of compounds in cinnamon which affect the hypothalamus-pituitary axis and has thus increased concentrations of these hormones. The researches done by Shagauo and Davidson GNAT2 [26] also showed that cinnamon is capable of releasing LH hormone by affecting hypothalamus axis and increasing the secretion rate of GnRH hormone. Also, they proposed that GnRH cause proliferation of sex cells by increasing the Leydig cell activities in adult rats. In another explanation, Parivzi and Ellendorff [27] showed that cinnamaldehyde extracted from cinnamon increase norepinephrine and this hormone can increase the release of nitric oxide. Cinnamaldehyde release cAMP with connecting calcium in cell membrane and cause increase in norepinephrine secretion. Norepinephrine increase LH secretion with activation of nitric oxide. Nitric oxide affects hypothalamus axis and release gonadotropin hormone (GnRH). Gonadotorpin hormones increase secretion of other hormones such as LH and FSH of pituitary gland. LH hormone affects Leydig cells and this cells release testosterone hormone.

e 23 9, 23 0 and 19 3 g m− 2 day− 1 The resulting average rate

e. 23.9, 23.0 and 19.3 g m− 2 day− 1. The resulting average rate of deposition per unit bottom surface area was 22.1 g m− 2 day− 1. This value is somewhat different from those calculated for other Baltic Sea regions where such investigations have been conducted. For comparison, the rates of vertical sediment influx in the Puck Lagoon – the shallowest, north-western corner of Puck Bay, situated near the town

of Puck – measured using sediment traps were 19.7, 46.9 and 21.3 g m− 2 day− 1. The highest rate related to the relatively deep Jama Rzucewska (Rzucewska Hollow), while the other two refer to shallow water regions of the Lagoon (Szymczak 2006). Investigations in the Pomeranian Bay showed in turn that vertical sediment influxes to the seabed were between 75 and 87 g m− 2 day− 1 (Jähmlich et al. 2002). Comparison of these GSK126 quantities with those from Table 2 shows that sediment accumulation in the Outer Puck Bay takes place under relatively calm conditions. The granulometric tests of the sediment deposited in the traps indicate that it can be classified as sandy mud and sand-clayey mud (Figure 3). This type of sediment selleck chemical is usually found in this part of the Puck Bay at depths of about 20 m (Jegliński et al. 2009). The grain size of the dominant mud fraction is 0.063–0.032 mm, while that of the prevailing sand fraction is 0.125–0.063 mm (Table 3). The results

of granulometric analysis indicate that the surface sediments belong to the clayey mud class (Figure 3). This type of sediment occurs in Puck Bay, locally forming a transition zone between the sand-mud-clay and muddy clay sediment types (Uścinowicz & Zachowicz 1994). Apart from the depths, slope and shoreline configuration that contribute to a large extent to local wave Fluorouracil supplier and current regimes, a factor exerting a substantial influence on the distribution of sediments in Puck Bay is the

Hel Peninsula (Uścinowicz & Zachowicz 1994). Sandy fractions are periodically transported into the deeper parts of Puck Bay when waves propagate from the west. The transported sediments probably originate from shallow areas adjacent to the Hel Peninsula (Passchier et al. 1997). The proportion of organic matter in the total volume of sediment deposited in the sediment traps varied slightly, between 10 and 11% (Table 4). These proportions are similar for all periods and are almost twice as high as those reported previously for Puck Bay sediments (Uścinowicz & Zachowicz 1993). This discrepancy can be explained by mineralisation processes: the amount of organic matter actually supplied to the seabed is greater than that recorded in the deposited sediments, because mineralisation gradually reduces the proportion of organic matter there. An alternative explanation is that the traps are ‘better’ at collecting material rich in organic matter, e.g. low density particles.

O presente estudo de custo-utilidade sobre o tratamento da HBC é

O presente estudo de custo-utilidade sobre o tratamento da HBC é o primeiro trabalho publicado sobre as opções terapêuticas mais comummente utilizadas tendo, como pano de fundo, a realidade nacional. Os resultados obtidos nesta análise indicam que o tratamento inicial com TDF é uma estratégia dominante, selleck screening library por comparação ao tratamento com ETV, quando ambos sequenciados pela terapêutica combinada TDF+ETV

nos casos de resistência ou não resposta. Ao gerar menores custos totais para uma efetividade semelhante (superior na análise determinística), a utilização de TDF, quando clinicamente viável, permite libertar recursos passíveis de utilização em fins alternativos geradores de resultados em saúde adicionais. Admitindo que 50% dos 1800 doentes em tratamento se encontram em primeira linha e que 50% destes fazem monoterapia com ETV, a poupança estimada gerada pela mudança destes doentes para TDF

seria de 5,3 milhões de Euros (10,4 milhões, sem atualização) no horizonte temporal considerado, ou seja, a esperança média de vida da coorte simulada. Estes resultados são coincidentes com os obtidos nos 2 estudos de avaliação económica publicados, comparando TDF a ETV no tratamento oral inicial da HBC44. Tanto o estudo de Buti et al.14, para Espanha, como o estudo de Dakin et al.13, para o Reino Unido, e o estudo de Colombo et al.45 concluem, à semelhança dos resultados obtidos no presente estudo, que a opção TDF resulta em menores custos totais para uma efetividade superior. this website Buti many et al. consideram a opção TDF+ETV em segunda linha obtendo diferenças em termos de AVAQs e custos na mesma ordem de grandeza das obtidas no presente estudo (0,178 AVAQs versus 0,04 AVAQs e −7886 € versus −11 865 €), embora seja de salientar que as taxas de atualização divergem nos 2 estudos. No estudo de Colombo et al., o horizonte temporal assumido é de 10 anos. No estudo de Dakin et al., os resultados relativos à estratégia de utilização de TDF+ETV em segunda linha não são reportados e nenhum dos estudos reporta as diferenças em termos dos restantes indicadores de resultados em saúde. Embora o modelo utilizado no presente

estudo represente um desenvolvimento face ao modelo de Buti et al.14 no que diz respeito às críticas apresentadas por Dusheiko46 (como a inclusão do impacto da taxa de progressão para cirrose em doentes AgHBe-negativo e a perda do AgHBs), um modelo é, por definição, uma simplificação da realidade cuja validade está limitada pelos dados disponíveis e pressupostos inerentes. Concretamente, no presente estudo são de salientar as limitações que abaixo se enunciam. Por um lado, a comparação entre medicamentos (TDF e ETV) não é direta. Os dados de eficácia utilizados no ramo ETV são os reportados num ensaio comparando ETV com lamivudina22, enquanto no ramo TDF foram utilizados os dados reportados no ensaio clínico que compara TDF com adefovir25, 29 and 47. Os testes utilizados, embora diferentes (TDF: Roche Amplicor v2.