Recommendations from GESIDA/SEFH/PNS to improve adherence to antiviral treatment (2004)

Since the early days of antiretroviral therapy, adherence has emerged as the milestone of success; in fact, it is the most potent predictor of effectiveness. The main factors related to adherence include the complexity of the therapeutic regimen, adverse effects, psychological problems, alcoholism and active addiction to drugs, lack of social and family support and the patient's beliefs and attitudes about the treatment. Adherence monitoring should be part of the HIV patient's regular care, and should be done with feasible, easily applied methods adapted to the different clinical settings. The minimally acceptable measures should include use of a validated questionnaire, together with data from the Pharmacy Department's drug dispensation registry. All patients that begin HAART or undergo a change of treatment should participate in a treatment education program imparted by health professionals with knowledge and experience in the management of patients with HIV infection. The health team (doctors, pharmacists and nursing professionals) should offer maximum availability to solve the doubts and problems that may occur during treatment. When sub-optimal adherence is detected, intervention strategies based on psychological therapy, educational efforts and personal advice should be attempted, in order to adapt the treatment scheme to the patient's habits and provide solutions to the problem of non-compliance. In certain situations, co-morbid conditions will also require attention. Treatment adherence, being a multidimensional problem, needs a multidisciplinary team approach. The choice of therapy, only one aspect of the multidimensional problem of adherence, must be a careful and individualized decision; however, simpler regimens with regard to the number of pills and daily dose are desirable.     

Increased nuclear ?-catenin expression in oral potentially malignant lesions: A marker of epithelial dysplasia

Background

Deregulation of ?-catenin is associated with malignant transformation; however, its relationship with potentially malignant and malignant oral processes is not fully understood. The aim of this study was to determine and compare the nuclear ?-catenin expression in oral dysplasia and oral squamous cell carcinoma (OSCC).

Material and Methods

Cross sectional study. Immunodetection of ?-catenin was performed on 72 samples, with the following distribution: 21 mild dysplasia, 12 moderate dysplasia, severe dysplasia 3, 36 OSCC including 19 well differentiated, 15 moderately differentiated and 2 poorly differentiated. Through microscopic observation the number of positive cells per 1000 epithelial cells was counted. For the statistical analysis, the Kruskal Wallis test was used.

Results

Nuclear expression of ?-catenin was observed in all samples with severe and moderate dysplasia, with a median of 267.5, in comparison to mild dysplasia whose median was 103.75. Only 10 samples (27.7%) with OSCC showed nuclear expression, with statistically significant differences between groups (p < 0.05).

Conclusions

Our results are consistent with most of the reports which show increased presence of ?-catenin in severe and moderate dysplasia compared to mild dysplasia; however the expression of nuclear ?-catenin decreased after starting the invasive neoplastic process. This suggests a role for this protein in the progression of dysplasia and early malignant transformation to OSCC. Immunodetection of ?-catenin could be a possible immune marker in the detection of oral dysplasia. Key words:Oral squamous cell carcinoma (OSCC), ?-catenin, oral dysplasia.     

Prevalence of diabetes mellitus and impaired glucose regulation in Spain: the Di@bet.es Study

Aims/hypothesis

The Di@bet.es Study is the first national study in Spain to examine the prevalence of diabetes and impaired glucose regulation.

Methods

A population-based, cross-sectional, cluster sampling study was carried out, with target population being the entire Spanish population. Five thousand and seventy-two participants in 100 clusters (health centres or the equivalent in each region) were randomly selected with a probability proportional to population size. Participation rate was 55.8%. Study variables were a clinical and demographic structured survey, lifestyle survey, physical examination (weight, height, BMI, waist and hip circumference, blood pressure) and OGTT (75?g).

Results

Almost 30% of the study population had some carbohydrate disturbance. The overall prevalence of diabetes mellitus adjusted for age and sex was 13.8% (95% CI 12.8, 14.7%), of which about half had unknown diabetes: 6.0% (95% CI 5.4, 6.7%). The age- and sex-adjusted prevalence rates of isolated impaired fasting glucose (IFG), isolated impaired glucose tolerance (IGT) and combined IFG?CIGT were 3.4% (95% CI 2.9, 4.0%), 9.2% (95% CI 8.2, 10.2%) and 2.2% (95% CI 1.7, 2.7%), respectively. The prevalence of diabetes and impaired glucose regulation increased significantly with age (p?p?Conclusions/interpretation The Di@bet.es Study shows, for the first time, the prevalence rates of diabetes and impaired glucose regulation in a representative sample of the Spanish population.     

Objectively-measured and self-reported physical activity and fitness in relation to inflammatory markers in European adolescents: the HELENA Study

ObjectiveAtherogenesis involves an inflammatory process that occurs early in life even though clinical symptoms are not observed until adulthood. Two important protective factors for low-grade inflammation may be physical activity (PA) and fitness. We examined the independent associations of objective and subjective measurements of PA and fitness with low-grade inflammation in European adolescents.MethodsA total of 1045 adolescents, aged from 12.5 to 17.5 years old from 10 European cities, were selected from the HELENA-Cross-Sectional Study. Objectively-measured and self-reported PA variables were obtained by accelerometry and the International PA Questionnaire for Adolescents, respectively. Overall, cardiorespiratory, muscular and motor fitness variables were assessed by standardized field-based fitness tests and the International Fitness Scale. C-reactive protein (CRP), complement factors 3 (C3) and 4 (C4), interleukin-6 and TNF-α inflammatory markers were measured.ResultsObjectively-measured vigorous PA was inversely associated with C3 (β = ?0.094, P = 0.021) but it did not remain significant after any objective fitness indicator was included in the model. Other objectively measured or self-reported assessments of PA were not significantly associated with inflammatory markers. All objective measures of fitness were inversely associated with CRP, C3 and C4, whereas only self-reported motor fitness remained significantly associated with C3, C4 and TNF-α. All these observations were independent of age, sex, city and body mass index or waist circumference.ConclusionHigh PA in adolescence may play an indirect role on lessening low-grade inflammation through improvements in fitness.     

Blocking ephrinB2 with highly specific antibodies inhibits angiogenesis, lymphangiogenesis, and tumor growth

Membrane-anchored ephrinB2 and its receptor EphB4 are involved in the formation of blood and lymphatic vessels in normal and pathologic conditions. Eph/ephrin activation requires cell-cell interactions and leads to bidirectional signaling pathways in both ligand- and receptor-expressing cells. To investigate the functional consequences of blocking ephrinB2 activity, 2 highly specific human single-chain Fv (scFv) Ab fragments against ephrinB2 were generated and characterized. Both Ab fragments suppressed endothelial cell migration and tube formation in vitro in response to VEGF and provoked abnormal cell motility and actin cytoskeleton alterations in isolated endothelial cells. As only one of them (B11) competed for binding of ephrinB2 to EphB4, these data suggest an EphB-receptor-independent blocking mechanism. Anti-ephrinB2 therapy reduced VEGF-induced neovascularization in a mouse Matrigel plug assay. Moreover, systemic administration of ephrinB2-blocking Abs caused a drastic reduction in the number of blood and lymphatic vessels in xenografted mice and a concomitant reduction in tumor growth. Our results show for the first time that specific Ab-based ephrinB2 targeting may represent an effective therapeutic strategy to be used as an alternative or in combination with existing antiangiogenic drugs for treating patients with cancer and other angiogenesis-related diseases.     

Evaluación económica de la elastografía de transición (FibroScan) en el diagnóstico de fibrosis hepática en pacientes con hepatitis C coinfectados con VIH

Introduction

The assessment of liver fibrosis is crucial for taking therapeutic decisions in patients infected with HIV/AIDS coinfected with HCV, because it allows the prognosis of the disease and the prioritization of hepatitis C treatment in these patients.

Methods

A discrete events model simulation (DEMS) and a Markov model have been developed to represent the evolution of liver fibrosis to cirrhosis in patients coinfected with HIV/HVC. The model evaluated two alternatives for the diagnosis and monitoring of these patients, transient elastography performed annually and liver biopsy performed every seven years. The models have been developed under Health Care System perspective and only considered direct medical costs (disease treatment and health state costs). One-way sensitivity analyses were carried out to assess the impact of parameters with higher uncertainty. A discount rate of 3% was applied.

Results

Base case analysis shows that the diagnosis and monitoring of patients with transient elastography is a dominant strategy compared with to liver biopsy, resulting in greater life expectancy at lower cost. The sensitivity analysis performed confirmed the robustness of these results.

Conclusion

Transient elastography has proved to be a dominant strategy compared to liver biopsy in the diagnosis and monitoring of liver fibrosis in patients coinfected with HIV/HCV in Spain.     

Documento de consenso sobre el fenotipo mixto EPOC-asma en la EPOC

Introduction

Although asthma and COPD are different pathologies, many patients share characteristics from both entities. These cases can have different evolutions and responses to treatment. Nevertheless, the evidence available is limited, and it is necessary to evaluate whether they represent a differential phenotype and provide recommendations about diagnosis and treatment, in addition to identifying possible gaps in our understanding of asthma and COPD.

Methods

A nation-wide consensus of experts in COPD in two stages: 1) during an initial meeting, the topics to be dealt with were established and a first draft of statements was elaborated with a structured «brainstorming» method; 2) consensus was reached with two rounds of e-mails, using a Likert-type scale.

Results

Consensus was reached about the existence of a differential clinical phenotype known as «Overlap Phenotype COPD-Asthma», whose diagnosis is made when 2 major criteria and 2 minor criteria are met. The major criteria include very positive bronchodilator test (increase in FEV₁ ≥ 15% and ≥ 400 ml), eosinophilia in sputum and personal history of asthma. Minor criteria include high total IgE, personal history of atopy and positive bronchodilator test (increase in FEV₁ ≥ 12% and ≥ 200 ml) on two or more occasions. The early use of individually-adjusted inhaled corticosteroids is recommended, and caution must be taken with their abrupt withdrawal. Meanwhile, in severe cases the use of triple therapy should be evaluated. Finally, there is an obvious lack of specific studies about the natural history and the treatment of these patients.

Conclusions

It is necessary to expand our knowledge about this phenotype in order to establish adequate guidelines and recommendations for its diagnosis and treatment.