The Impact of CAROtid plaque Screening on Smoking (CAROSS) cessation and control of other cardiovascular risk factors: rationale and design of a randomized controlled trial

BACKGROUND: Screening tests for subclinical cardiovascular disease, such as markers of atherosclerosis, are increasingly used in clinical prevention to identify individuals at high cardiovascular risk. Being aware of these test results might also enhance patient motivation to change unhealthy behaviors but the effectiveness of such a screening strategy has been poorly studied. METHODS: The CAROtid plaque Screening trial on Smoking cessation (CAROSS) is a randomized controlled trial in 530 regular smokers aged 40-70 years to test the hypothesis that carotid plaque screening will influence smokers' behavior with an increased rate of smoking cessation (primary outcome) and an improved control of other cardiovascular risk factors (secondary outcomes) after 1-year follow-up. All smokers will receive a brief advice for smoking cessation,and will subsequently be randomly assigned to either the intervention group (with plaques screening) or the control group (without plaque screening). Carotid ultrasound will be conducted with a standard protocol. Smokers with at least one carotid plaque will receive pictures of their own plaques with a structured explanation on the general significance of plaques. To ensure equal contact conditions, smokers not undergoing ultrasound and those without plaque will receive a relevant explanation on the risks associated with tobacco smoking. Study outcomes will be compared between smokers randomized to plaque screening and smokers not submitted to plaque screening. SUMMARY: This will be the first trial to assess the impact of carotid plaque screening on 1-year smoking cessation rates and levels of control of other cardiovascular risk factors.

Epidemiological and control aspects of schistosomiasis in Brazilian endemic areas

The present work analyzes the epidemiology of schistosomiasis in Brazil, its expansion, the attempts to control the disease, and the overall difficulties. The authors present the distribution of schistosomiasis intermediary hosts in Brazil, the migration routes of the human population, and disease distribution in highly and lowly endemic areas and isolated foci. They also analyze the controlling programs developed from 1977 to 2002, indicating the prevalence evolution and the reduction of disease morbi-mortality. In addition, the authors also evaluate controlling methods and conclude that: (a) no isolated method is able to control schistosomiasis, and every controlling program should consider the need of a multidisciplinary application of existing methods; (b) in long term, basic sanitation, potable water supply, as well as sanitary education, and community effective participation are important for infection control; (c) in short term, specific treatment at endemic areas, associated with control of intermediary hosts at epidemiologically important foci, are extremely relevant for controlling disease morbidity, although not enough for interrupting infection transmission.

Low transmission areas of schistosomiasis in Venezuela: consequences on the diagnosis, treatment, and control

Schistosomiasis low transmission areas as Venezuela, can be defined as those where the vector exists, the prevalence of active cases is under 25%, individuals with mild intensity of infection predominate and are mostly asymptomatic. These areas are the consequence of effective control programs, however, "silent" epidemiological places are difficult to trace, avoiding the opportune diagnosis and treatment of infected persons. Clinic and abdominal ultrasound have not shown to discriminate infected from uninfected persons in areas where besides Schistosoma mansoni, intestinal parasites are the rule. Under these conditions, serology remains as a very valuable diagnostic tool, since it gives a closer approximation to the true prevalence. In this sense, circumoval precipitin test, ELISA-SEA with sodium metaperiodate, and alkaline phosphatase immunoassay joined to coprology allow the identification of the "schistosomiasis cases". In relation to public health, schistosomiasis has been underestimated by the sanitary authorities and the investment on its control is being transferred to other diseases of major social and political relevance neglecting sanitary efforts and allowing growth of snail population. Some strategies of diagnosis and control should be done before schistosomiasis reemergence occurs in low transmission areas.

Population pharmacokinetics of imatinib in CML and GIST patients under long-term treatment

Imatinib (Glivec®) has transformed the treatment and short-term prognosis of chronic myeloid leukaemia (CML) and gastrointestinal stromal tumour (GIST). However, the treatment must be taken indefinitely and is not devoid of inconvenience and toxicity. Moreover, resistance or escape from disease control occurs in a significant number of patients. Imatinib is a substrate of the cytochromes P450 CYP3A4/5 and of the multidrug transporter P glycoprotein (product of the MDR1 gene), and is also bound to the alpha1-acid glycoprotein (AAG) in plasma. Considering the large inter-individual differences in the expression and function of those systems, the disposition and clinical activity of imatinib can be expected to vary widely among patients, calling for dosage individualisation. The aim of this exploratory study was to determine the average pharmacokinetic parameters characterizing the disposition of imatinib in the target population, to assess their inter-individual variability, and to identify influential factors affecting them. A total of 321 plasma concentrations were measured in 59 patients receiving Glivec® at diverse dosage regimens, using a validated chromatographic method developed for this study. The results were analysed by non-linear mixed effect modelling (NONMEM). A one-compartment model with first-order absorption described the data appropriately, with an average apparent clearance of 12.4 l/h, a volume of distribution of 268 l and an absorption constant of 0.47 h-1. The clearance was affected by body weight, age and sex. No influences of interacting drugs were found. DNA samples were used for pharmacogenetic explorations. The MDR1 polymorphism 3435C>T and the AAG phenotype appears to modulate the disposition of imatinib. Large inter-individual variability (CV %) remained unexplained by the demographic covariates considered, both on clearance (40%) and distribution volume (71%). Together with intra-patient variability (34%), this translates into an 8-fold width of the 90%-prediction interval of plasma concentrations expected under a fixed dosing regimen. This is a strong argument to further investigate the possible usefulness of a therapeutic drug monitoring programme for imatinib. It may help in individualising the dosing regimen before overt disease progression or observation of treatment toxicity, thus improving both the long-term therapeutic effectiveness and tolerability of this drug.

Prevalence, awareness, treatment and control of high blood pressure in a Swiss city general population: the CoLaus study.

BACKGROUND: This study is aimed to assess the prevalence of awareness, treatment and control of high blood pressure (HBP) and associated factors in a Swiss city. DESIGN: Population-based cross-sectional study of 6182 participants (52.5% women) aged 35-75 years living in Lausanne, Switzerland. METHODS: HBP was defined as blood pressure >/=140/90 mmHg or current antihypertensive medication. RESULTS: The overall prevalence of HBP was 36% (95% confidence interval: 35-38%). Among participants with HBP, 63% were aware of it. Among participants aware of HBP, 78% were treated, and among those treated, 48% were controlled (BP <140/90 mmHg). In multivariate analysis, HBP prevalence was associated with older age, male sex, low educational level, high alcohol intake, awareness of diabetes or dyslipidaemia, obesity and parental history of myocardial infarction. HBP awareness was associated with older age, female sex, awareness of diabetes or dyslipidaemia, obesity and parental history of myocardial infarction. HBP control was associated with younger age, higher educational level and no alcohol intake. Alone or in combination, sartans were the most often prescribed antihypertensive medication category (41%), followed by diuretics, beta-blockers, angiotensin converting enzyme inhibitors and calcium channel blockers. Only 31% of participants treated for HBP were taking >/=2 antihypertensive medications. CONCLUSION: Although more than half of all participants with HBP were aware and more than three-quarters of them received a pharmacological treatment, less than half of those treated were adequately controlled.

Biology, diversity and strategies for the monitoring and control of triatomines - Chagas disease vectors

Despite the relevant achievements in the control of the main Chagas disease vectors Triatoma infestans and Rhodnius prolixus, several factors still promote the risk of infection. The disease is a real threat to the poor rural regions of several countries in Latin America. The current situation in Brazil requires renewed attention due to its high diversity of triatomine species and to the rapid and drastic environmental changes that are occurring. Using the biology, behaviour and diversity of triatomines as a basis for new strategies for monitoring and controlling the vectorial transmission are discussed here. The importance of ongoing long-term monitoring activities for house infestations by T. infestans, Triatoma brasiliensis, Panstrongylus megistus, Triatoma rubrovaria and R. prolixus is also stressed, as well as understanding the invasion by sylvatic species. Moreover, the insecticide resistance is analysed. Strong efforts to sustain and improve surveillance procedures are crucial, especially when the vectorial transmission is considered interrupted in many endemic areas.

The role of population movement in the epidemiology and control of schistosomiasis in Brazil: a preliminary typology of population movement

This paper examines recent developments in migration studies. It reviews literature related to the potential role of internal population movement in the occurrence of schistosomiasis in Brazil and modifies Prothero's typology of population movement for use in Brazil. This modified classification system may contribute to a better understanding of schistosome transmission as well as improved research and control programs. The results of this study indicate that population movement in Brazil primarily involves economically-motivated rural-urban and interregional movement. However, several movement patterns have become increasingly important in recent years as a result of changing socioeconomic and urbanisation dynamics. These patterns include urban-urban, intracity and urban-rural movement as well as the movement of environmental refugees and tourists. Little is known about the epidemiological significance of these patterns. This paper also highlights the role of social networks in the decision to migrate and to settle. Prothero's classic population movement typology categorises movement as either one-way migrations or circulations and examines them along spatial and temporal scales. However, the typology must be modified as epidemiological information about new patterns becomes available. This paper identifies areas that require further research and offers recommendations that can improve the measurement and spatial analysis of the relationship between population movement and schistosomiasis.

Sylvatic foci of the Chagas disease vector Triatoma infestans in Chile: description of a new focus and challenges for control programs

Triatoma infestans is one of the main domestic vectors of Chagas disease. Reports of wild habitat occurrences have recently increased. In Chile, after a successful elimination campaign of T. infestans domestic infestation, a sylvatic focus was reported in bromeliads in the metropolitan region. Here, we report a new focus of sylvatic T. infestans inhabiting rock piles in the Valparaíso region in central Chile. All T. infestans captured were nymphal instars living among the stones, which were inhabited by several mammal species, along with the sylvatic triatomine vector Mepraia spinolai. We found a prevalence of infection with Trypanosoma cruzi of 36.54% in T. infestans, similar to the previous report for sylvatic specimens from bromeliads. Sylvatic populations of T. infestans should be studied at different geographic scales to elucidate their role in the maintenance of the sylvatic transmission cycle of T. cruzi and their possible role in threatening the domestic elimination of this vector. This information should be used to re-design the control programs in Chile to avoid the re-establishment of the domestic cycle.

Notch signaling in the integrated control of keratinocyte growth/differentiation and tumor suppression.

Oncogenesis is closely linked to abnormalities in cell differentiation. Notch signaling provides an important form of intercellular communication involved in cell fate determination, stem cell potential and differentiation. Here we review the role of this pathway in the integrated growth/differentiation control of the keratinocyte cell type, and the maintenance of normal skin homeostasis. In parallel with the pro-differentiation function of Notch1 in keratinocytes, we discuss recent evidence pointing to a tumor suppressor function of this gene in both mouse skin and human cervical carcinogenesis. The possibility that Notch signaling elicits signals with a duality of growth positive and negative function will be discussed.