In overweight patients with chronic hepatitis C, circulating insulin is associated with hepatic fibrosis: implications for therapy

Background/Aims: Host factors such as increased body mass index (BMI) and genotype-specific viral factors contribute to the development of steatosis in patients with chronic hepatitis C (HCV). We hypothesized that host metabolic factors associated with increased BMI may play a role in disease progression. Methods: Fasting serum was collected from 160 patients with chronic HCV at the time of liver biopsy and 45 age, gender and BMI matched controls, and assessed for levels of insulin, c-peptide and leptin. Results: Patients with viral genotype 3 had more severe steatosis (P = 0.0001) and developed stages 1 and 2 fibrosis at a younger age (P < 0.05) than patients with genotype 1. For both genotypes, overweight patients had significantly more steatosis and increased insulin and leptin levels. In contrast to lean patients, there was a statistically significant increase in circulating insulin levels with increasing fibrosis in overweight patients with chronic HCV (P = 0.03). Following multivariate analysis, insulin was independently associated with fibrosis (P = 0.046) but not inflammation (P = 0.83). There was no association between serum leptin levels and stage of fibrosis. Conclusions: Increasing circulating insulin levels may be a factor responsible for the association between BMI and fibrosis in patients with HCV, irrespective of viral genotype. (C) 2003 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Left ventricular dyssynchrony predicts benefit of cardiac resynchronization therapy in patients with end-stage heart failure before pacemaker implantation

We evaluated patients with end-stage heart failure who have a high likelihood of response to cardiac resynchronization therapy (biventricular pacing). It appears that 20% of patients do not respond to this expensive therapy despite the use of selection criteria (dilated cardiomyopathy, heart failure, New York Heart Association class II or IV, left ventricular election fraction 120 ms). The presence of left ventricular dys-synchrony is needed to result in improvement after cardiac resynchronization therapy. (C)2003 by Excerpta Medica, Inc.

Transition to raloxifene with and without low-dose estrogen therapy in postmenopausal women: effects on serum lipids and fibrinogen - a pilot study

Objective To compare the effects of transferring from low-dose transdermal estrogen to raloxifene (RLX), with a phase of alternate-day RLX therapy with or without low-dose transdermal estrogen, on serum lipids and fibrinogen in postmenopausal women previously administered estrogen plus progestogen therapy. Methods Sixty postmenopausal women (mean age 55 years) were randomized to one of two treatment groups: RLX + low-dose transdermal estrogen (RLX + E) or RLX + placebo. The study consisted of four 8-week phases: phase I (all subjects low-dose transdermal estrogen 25 mug/day), phase II (double-blind RLX 60 mg every 2nd day in combination with either low-dose transdermal estrogen or placebo), phase III (all subjects RLX 60 mg every 2nd day + placebo) and phase IV (all subjects RLX 60 mg/day + placebo). Results No significant differences existed between groups for baseline measurements prior to phase I. In phase I, for all subjects combined, total cholesterol and low-density lipoprotem cholesterol both showed a significant increase (median increase of 0.2 mmol/l, p = 0.008 and 0.4 mmol/l, p < 0.001, respectively), while triglycerides decreased significantly (median decrease of 0.2 mmol/l, p < 0.001). For the primary analysis (phase II to phase IV), the mean change from baseline observations showed no significant differences between the therapy groups for serum lipids, fibrinogen, vital signs or weight. In the comparison phase (phase II), changes in serum lipids, fibrinogen, vital signs and weight were not significantly different between groups. Conclusion Gradual conversion to RLX from low-dose transdermal estrogen, with a phase of alternate-day RLX therapy with or without low-dose transdermal estrogen, does not have any effect on the serum lipid profile or fibrinogen level.

Factors influencing amblyopia rehabilitation in occlusive therapy

Amblyopia develops in an early period and is a decrease of visual acuity (unilateral or bilateral) caused by a deprivation of vision or abnormal binocular interaction. Prognosis of Amblyopia is better when occlusive treatment is implemented in an early stage. Visual acuity of amblyopic eye does not improve without effective occlusive therapy. The aim of this study is to identify potential risk factors of noncompliance with treatment when it is implemented by parents in amblyopic children.

Risk factors for non compliance using occlusive therapy: a case study

Purpose: compliance with treatment is a common problem when treating amblyopic patients. Visual acuity of amblyopic eye does not improve without effective occlusive therapy. The aim of this study is to identify potential risk factors of non-compliance with treatment when it is implemented by family in amblyopic children. Setting: a quantitative transversal study was performed in a public hospital and in a private clinic in Lisbon.

Drug therapy complexity: the importance of pharmacotherapeutic follow-up

Nowadays, the phenomenon of population ageing represents an worldwide problem, which assumes particular significance in Portugal. As they get older, individuals present more comorbidities and consequently consume an increasing number of drugs, which contributes to a growing drug therapy complexity. The institutionalized elders are particularly affected by this occurrence. Drug therapy complexity is defined as the conciliator of several characteristics of the pharmacotherapy and can affect patient’s safety and medication adherence. It can be measured with Medication Regimen Complexity Index (MRCI). This study aims to determine the drug therapy complexity of institutionalized elders in order to assess the need of pharmacotherapeutic follow-up.

Alternative regimens for prostate cancer treatment using radiation therapy

Purpose/Objective: The purpose of this work was to determine biologically equivalent alternative regimens for the treatment of prostate cancer using External Beam Radiotherapy (EBRT) and Low Dose-Rate Brachytherapy (LDRBT) with 125I implants and to evaluate the sensitivity of these regimens to different sets of radiobiological parameters of the Linear-Quadratic (LQ) model.

Implementation of proton therapy in the portuguese context of radiotherapy

Cancer is a national and international health care concern. It’s important to find strategies for early diagnosis as well as for the optimization of the various therapeutic options currently existing in Portugal. Cancer is the second leading cause of death in Portugal, the choice of this study, is due to the importance of radiotherapy approach in cancer treatment and because is the therapy used in 40% of oncology patients. Radiation therapy has evolve data technological level, that allows new treatment techniques that are more efficient and that also promotes greater professional satisfaction. The hadrons are charged particles, used in cancer therapy. These particles can bring a paradigm shift regarding the therapeutic approach in radiotherapy. The technique used is proton therapy, that reveal to be more accurate, efficacious and less toxic to surrounding tissue. Proton therapy may be a promising development in the field of oncology and how the treatment is given in radiotherapy. Although there is awareness of the benefits of proton therapy in oncology it’s also important to take in consideration the costs of these therapy, because they are considerably higher than conventional treatments of radiotherapy. Given the lack of a proton therapy service in Portugal, this study aims to be a documentary analysis of clinical records that will achieve the following objectives: to identify the number of cancer patients diagnosed in 2010 in Portugal and to calculate the estimated number of patients that could have been treated with proton therapy according to the Health Council of the Netherlands registration document.

Functional Assessment of Cancer Therapy Bone Marrow Transplantation: tradução e validação

OBJETIVO: Traduzir para o português e validar o questionário de qualidade de vida Functional Assessment of Cancer Therapy - Bone Marrow Transplantation (FACT-BMT) em pacientes transplantados de medula óssea. OBJETIVO: O estudo foi realizado em Ribeirão Preto, SP, em 2005. O FACT-BMT (versão 3) traduzido e a versão em português do Short Form-36 Health Survey (SF-36) foram aplicados simultaneamente em 55 pacientes consecutivos com leucemia, submetidos ao transplante e em seguimento. Dois parâmetros clínicos foram utilizados para testar a sensibilidade do questionário: tempo decorrido do transplante e presença ou não de doença do enxerto contra o hospedeiro. Foi utilizada a análise de variância (ANOVA) com o teste post hoc de Tukey. Aplicou-se o coeficiente alfa de Cronbach, padronizado para todas as questões, escore final e domínios. RESULTADOS: A média de idade dos pacientes foi 34,8±8,1 anos, com escolaridade média de 10,8±4,7 anos, sendo 78,1% do sexo feminino. A duração média de tempo pós-transplante foi de 29,8±32,19 meses. Nenhuma alteração do formato original do questionário foi observada no final do processo de tradução e adaptação cultural. A consistência interna foi alta (0,88). A correlação entre o questionário traduzido e o SF-36 variou de 0,35 a 0,57, considerada de moderada a boa para a maioria dos domínios de qualidade de vida. A avaliação das validades de construto e concorrente foi satisfatória e estatisticamente significativa. CONCLUSÕES: A versão para o português do FACT-BMT foi validada satisfatoriamente para a aplicação em pacientes brasileiros de ambos os sexos submetidos ao transplante de medula óssea.

Comparison of different breast planning techniques and algorithms for radiation therapy treatment

This work aims at investigating the impact of treating breast cancer using different radiation therapy (RT) techniques – forwardly-planned intensity-modulated, f-IMRT, inversely-planned IMRT and dynamic conformal arc (DCART) RT – and their effects on the whole-breast irradiation and in the undesirable irradiation of the surrounding healthy tissues. Two algorithms of iPlan BrainLAB treatment planning system were compared: Pencil Beam Convolution (PBC) and commercial Monte Carlo (iMC). Seven left-sided breast patients submitted to breast-conserving surgery were enrolled in the study. For each patient, four RT techniques – f-IMRT, IMRT using 2-fields and 5-fields (IMRT2 and IMRT5, respectively) and DCART – were applied. The dose distributions in the planned target volume (PTV) and the dose to the organs at risk (OAR) were compared analyzing dose–volume histograms; further statistical analysis was performed using IBM SPSS v20 software. For PBC, all techniques provided adequate coverage of the PTV. However, statistically significant dose differences were observed between the techniques, in the PTV, OAR and also in the pattern of dose distribution spreading into normal tissues. IMRT5 and DCART spread low doses into greater volumes of normal tissue, right breast, right lung and heart than tangential techniques. However, IMRT5 plans improved distributions for the PTV, exhibiting better conformity and homogeneity in target and reduced high dose percentages in ipsilateral OAR. DCART did not present advantages over any of the techniques investigated. Differences were also found comparing the calculation algorithms: PBC estimated higher doses for the PTV, ipsilateral lung and heart than the iMC algorithm predicted.

A comprehensive approach to evaluate nutritional status in Crohn's patients in the era of biologic therapy: a case-control study

Objectives - Evaluate the nutritional status of patients with inactive or mildly active Crohn's disease (CD), and identify possible causes for potential deficiencies. Methods - A total of 78 CD patients and 80 healthy controls were evaluated in respect of nutritional status, dietary intake, and life styles factors. Results - These 73/78 CD patients were on immunomodulating therapies. Mean body mass index (BMI) was lower in patients as compared to controls (P= 0.006) but 32% of CD patients and 33.8% of controls had a BMI > 25, whereas 8% and 23.8% in each group, respectively, were obese (BMI > 30Kg/m(2)). Fat free mass was significantly decreased in both genders (P < 0.05) whereas fat mass was decreased only in males (P= 0.01). Energy intake was significantly lower in CD patients (P < 0.0001) and we observed significantly lower adjusted mean daily intakes of carbohydrates, monounsaturated fat, fiber, calcium, and vitamins C, D, E, and K (P < 0.05). 29% of patients had excluded grains from their usual diet, 28% milk, 18% vegetables, and 11% fruits. Milk exclusion resulted in a significantly lower consumption of calcium and vitamin K (P < 0.001) and the exclusion of vegetables was associated to a lower consumption of vitamins C and E (P < 0.05). Physical activity was significantly lower in CD patients (P= 0.01) and this lack of physical activity was inversely correlated with increased fat mass percentage (r=-0.315, P= 0.001). Conclusions - Results showed that the most prevalent form of malnutrition in CD patients was an excess of body weight, which was concomitant with an inadequate dietary intake, namely micronutrients, clearly related to dietary exclusion of certain foods.

IL23R polymorphisms influence phenotype and response to therapy in patients with ulcerative colitis

Objective - We aimed to identify the clinical and genetic [IL23 receptor (IL23R) single nucleotide polymorphisms (SNPs)] predictors of response to therapy in patients with ulcerative colitis. Patients and methods - A total of 174 patients with ulcerative colitis, 99 women and 75 men, were included. The mean age of the patients was 47±15 years and the mean disease duration was 11±9 years. The number of patients classified as responders (R) or nonresponders (NR) to several therapies was as follows: 110 R and 53 NR to mesalazine (5-ASA), 28 R and 20 NR to azathioprine (AZT), 18 R and 7 NR to infliximab. Clinical and demographic variables were recorded. A total of four SNPs were studied: IL23R G1142A, C2370A, G43045A, and G9T. Genotyping was performed by real-time PCR using Taqman probes. Results - Older patients were more prone to respond to 5-ASA (P=0.004), whereas those with pancolitis were less likely to respond to such therapies (P=0.002). Patients with extraintestinal manifestations (EIMs) were less likely to respond to 5-ASA (P=0.001), AZT (P=0.03), and corticosteroids (P=0.06). Carriers of the mutant allele for IL23R SNPs had a significantly higher probability of developing EIMs (P<0.05), a higher probability of being refractory to 5-ASA (P<0.03), but a higher likelihood of responding to AZT (P=0.05). A significant synergism was observed between IL23R C2370A and EIMs with respect to nonresponse to 5-ASA (P=0.03). Conclusion - Besides extent of disease and age at disease onset, the presence of EIMs may be a marker of refractoriness to 5-ASA, corticosteroids, and AZT. IL23R SNPs are associated both with EIMs and with nonresponse to 5-ASA and corticosteroids.