Guidelines for the clinical management of atrial fibrillation: a practical perspective.

Since the management of atrial fibrillation may be difficult in the individual patient, our purpose was to develop simple clinical recommendations to help the general internist manage this common clinical problem. Systematic review of the literature with evaluation of data-related evidence and framing of graded recommendations. Atrial fibrillation affects some 1% of the population in Western countries and is linked to a significant increase in morbidity and mortality. The management of atrial fibrillation requires individualised evaluation of the risks and benefits of therapeutic modalities, relying whenever possible on simple and validated tools. The two main points requiring a decision in clinical management are 1) whether or not to implement thromboembolic prevention therapy, and 2) whether preference should be given to a "rate control" or "rhythm control" strategy. Thromboembolic prophylaxis should be prescribed after individualised risk assessment: for patients at risk, oral anticoagulation with warfarin decreases the rate of embolic complications by 60% and aspirin by 20%, at the expense of an increased incidence of haemorrhagic complications. "Rate control" and "rhythm control" strategies are probably equivalent, and the choice should also be made on an individualised basis. To assist the physician in making his choices for the care of an atrial fibrillation patient we propose specific tables and algorithms, with graded recommendations. On the evidence of data from the literature we propose simple algorithms and tables for the clinical management of atrial fibrillation in the individual patient.

Coronary magnetic resonance angiography.

Despite advances in both prevention and treatment, cardiovascular disease remains the leading cause of morbidity and mortality in the United States. The current gold standard for the diagnosis of coronary artery disease is the x-ray coronary angiogram, which is both costly and associated with a small risk of morbidity. More than 1 million Americans are referred for this test annually, and despite the availability of numerous noninvasive tests to identify patients with coronary artery disease, > or =35% of patients referred for this test are found not to have disease. It therefore would be beneficial to use a noninvasive test to allow the presence of coronary atherosclerosis to be determined directly. Coronary magnetic resonance angiography, a technique that is aimed at establishing a noninvasive test for the assessment of significant coronary stenoses, obviates the risks of patient exposure to radiation of x-ray angiography and therefore represents a major step forward in diagnostic cardiology.

Impact of Antifibrotic Treatment on the Course of Schistosoma mansoni Infection in Murine Model

Administration of an antifibrotic agent as an adjunct to antihelmintic treatment with the objective of morbidity reduction was investigated in the murine schistosomiasis mansoni model. Antifibrotic, ß-aminopropionitrile treatment has a profound effect on the cellular matrix composition of the liver granuloma of Schistosoma mansoni infected mice when given alone, resulting in increase macrophage infiltration. These macrophages, in response to stimulation with soluble egg antigen or lipopolysaccharide produced elevated levels of nitric oxide but low levels of tumor necrosis factor alpha compared to untreated infected mice. This also correlated with reduced liver granuloma size. In spite of low numbers of eggs in the liver, mice receiving a combine treatment had a high level of resistance to a challenge infection compared with mice receiving only praziquantel. Those mice also exhibited a reduced lymphocyte proliferative response, similar to that of infected untreated mice. Antifibrotic treatment has an impact on the dynamic of the cellular nature of granulomas and impacts on the host immunity to infection

The WHO Collaborating Centre for Research and Control of Schistosomiasis at Niamey, Niger

The Centre de Recherche sur les Méningites et les Schistosomes (CERMES) is a research institute depending on the Organisation de Coordination et de Coopération pour la lutte contre les Grandes Endémies - a West African Organization for Public Health - devoted to the studies on schistosomiasis and meningitis. The staff includes 32 persons with 11 scientists and one financial officer. The activities of the CERMES involving schistosomiasis concern three research units: (a) ecology of human and animal schistosomiasis transmission; the CERMES defined the different patterns of schistosomiasis transmission in Niger (involving African dry savana); in this field, we have shown, (i) the existence of important variability in conditions of transmission of S. haematobium and, (ii) natural hybridization between parasitic species of the ruminants (S. bovis and S. curassoni) and genetic interaction between human and animal parasites; (b) definition of morbidity indicators usable for rapid assessment methods, for appraisal of the severity of the disease and for the evaluation of the efficiency of control methods; we have established the correlation between ultrasonographic data and some cheap and simple field indicators; (c) immune response and protective immunity induced by recombinant glutathion S-transferase (Sm28, Sb28 and Sh28) in homologous and heterologous animal models including goats, sheep and non human primates (Erythrocebus patas). In Niger, we participate in all control programs against schistosomiasis to define control strategies, to supervise operations and to participate in their evaluation with external experts. International collaborations constitute a frame including four laboratories in Africa and six laboratories in developed countries (Europe and USA)

Cellular immune responses to HCV core increase and HCV RNA levels decrease during successful antiretroviral therapy.

BACKGROUND: Hepatitis C virus (HCV) infection is a major cause of morbidity in HIV infected individuals. Coinfection with HIV is associated with diminished HCV-specific immune responses and higher HCV RNA levels. AIMS: To investigate whether long-term combination antiretroviral therapy (cART) restores HCV-specific T cell responses and improves the control of HCV replication. METHODS: T cell responses were evaluated longitudinally in 80 HIV/HCV coinfected individuals by ex vivo interferon-gamma-ELISpot responses to HCV core peptides, that predominantly stimulate CD4(+) T cells. HCV RNA levels were assessed by real-time PCR in 114 individuals. RESULTS: The proportion of individuals with detectable T cell responses to HCV core peptides was 19% before starting cART, 24% in the first year on cART and increased significantly to 45% and 49% after 33 and 70 months on cART (p=0.001). HCV-specific immune responses increased in individuals with chronic (+31%) and spontaneously cleared HCV infection (+30%). Median HCV RNA levels before starting cART were 6.5 log(10) IU/ml. During long-term cART, median HCV-RNA levels slightly decreased compared to pre-cART levels (-0.3 log10 IU/ml, p=0.02). CONCLUSIONS: Successful cART is associated with increasing cellular immune responses to HCV core peptides and with a slight long-term decrease in HCV RNA levels. These findings are in line with the favourable clinical effects of cART on the natural history of hepatitis C and with the current recommendation to start cART earlier in HCV/HIV coinfected individuals.

Adaptable pulmonary artery band for late arterial switch procedure in transposition of the great arteries.

BACKGROUND: In late-diagnosed transposition of the great arteries (TGA), the left ventricle (LV) involutes as it pumps against low resistance and needs retraining by applying a pulmonary artery band (PAB) in preparation for an arterial switch operation. We report our experience with a telemetrically adaptable band compared with classic banding. METHODS: Ten patients underwent retraining of the LV, 4 patients with an adaptable band and progressive weekly tightening of the band (group 1) and 6 patients with a traditional band (group 2). RESULTS: Mean weight and age at pulmonary band placement was 5.8 ± 2.36 kg and 11.7 ± 11.1 months for group 1 and 5.0 ± 2.3 kg and 6.4 ± 7.6 months for group 2. Time between palliation and switch procedure was 4.2 months in both groups. Group 1 showed an initial mean pulmonary gradient of 25.5 ± 4.43 mm Hg with a 5% closure of the device. The mean gradient increased with progressive closure to 63.5 ± 9.8 mm Hg at the time of the arterial switch operation. There were no reinterventions or deaths in this group. In group 2, the mean pulmonary gradient increased with growth from 49 ± 21.4 mm Hg to 68.4 ± 7.86 mm Hg at the time of the switch procedure. However, 4 of these patients required reoperations during retraining: 2 needed 1 reoperation and 2 needed 2 reoperations. Two patients died-1 after banding and 1 after the switch operation. CONCLUSIONS: Retraining of the LV by the adaptable device allows precise control of the tightening, avoids repetitive operations, and diminishes morbidity.

Immunization of Persons with HIV Infection and other Secondary Immunodeficiencies

Patients with secondary immunodeficiencies are at a high risk of infection. Currently some of these infections are preventable through specific immunization. Prevention of these diseases can diminish morbidity and mortality amongst these patients. In this review we describe the use of vaccines in persons with secondary immunodeficiencies.

Urologie [Trends in urology]

The systemic treatment of kidney cancers is promising regarding the first results of the inhibiting molecules of the angiogenesis. Projections in research are encouraging for more specific and sensitive markers of the prostate cancer. For this last the intermittent hormonotherapy improves the quality of life of the patients. The overweight control in infertility allows greater chances of giving birth. The morbidity of the kidney percutaneous surgery is decreased by the use of smaller tools. Reduction rate of reobstruction thanks to new manufactoring stents. The botulinic toxin for the hyperactive bladder refunded by the health insurances.

Schistosomiasis control in Brazil

In 1975 the Special Programme for Schistosomiasis Control was introduced in Brazil with the objective of controlling this parasitic disease in six northeastern states. The methodology applied varied largely from state to state, but was based mainly on chemotherapy, This Programme was modified about ten years after it beginning with the main goals including control of morbidity and the blockage of establishment of new foci in non-endemic areas. In two states, Bahia and Minas Gerais, the schistosomiasis control programme started in 1979 and 1983, respectively. The recently made evaluation of those two programmes is the main focus of this paper. It must also be pointed out, that the great majority of the studies performed by different researchers in Brazil, at different endemic areas, consistently found significant decrease on prevalence and incidence, when control measures are repeatedly used for several years. Significant decrease of hepatosplenic forms in the studied areas is well documented in Brazil. After more than 20 years of schistosomiasis control programmes in our country, chemotherapy has shown to be a very important tool for the control of morbidity and to decrease prevalence and incidence in endemic areas. Nevertheless, in medium and long terms, sanitation, water supply, sewage draining and health education seem to be the real tools when the aim is persistent and definitive schistosomiasis control.

Different approaches to modelling the cost-effectiveness of schistosomiasis control

This paper reviews three different approaches to modelling the cost-effectiveness of schistosomiasis control. Although these approaches vary in their assessment of costs, the major focus of the paper is on the evaluation of effectiveness. The first model presented is a static economic model which assesses effectiveness in terms of the proportion of cases cured. This model is important in highlighting that the optimal choice of chemotherapy regime depends critically on the level of budget constraint, the unit costs of screening and treatment, the rates of compliance with screening and chemotherapy and the prevalence of infection. The limitations of this approach is that it models the cost-effectiveness of only one cycle of treatment, and effectiveness reflects only the immediate impact of treatment. The second model presented is a prevalence-based dynamic model which links prevalence rates from one year to the next, and assesses effectiveness as the proportion of cases prevented. This model was important as it introduced the concept of measuring the long-term impact of control by using a transmission model which can assess reduction in infection through time, but is limited to assessing the impact only on the prevalence of infection. The third approach presented is a theoretical framework which describes the dynamic relationships between infection and morbidity, and which assesses effectiveness in terms of case-years prevented of infection and morbidity. The use of this model in assessing the cost-effectiveness of age-targeted treatment in controlling Schistosoma mansoni is explored in detail, with respect to varying frequencies of treatment and the interaction between drug price and drug efficacy.

Hypertension. L'etude ACCOMPLISH: des résultats vraiment inattendus [The ACCOMPLISH trial: are results really unexpected?]

The ACCOMPLISH trial consists of a randomized morbidity-mortality study involving 11506 hypertensive patients at high cardiovascular risk, randomly allocated to a fixed dose combination containing an angiotensin converting enzyme inhibitor (B, benazepril) and either a calcium antagonist (A, amlodipine) or a diuretic (HCTZ, hydrochlorothiazide). The target blood pressure (< 140/90 mmHg) was achieved after a 6 month titration period in 75.4% of patients receiving B+A, versus 72.4% in those on B + HCTZ. Over a mean follow-up of 3 years, the B + A drug regimen was found to reduce significantly more effectively the relative risk cardiovascular mortality (-20%), fatal and non fatal myocardial infarction (-22%) and coronary revascularization (-14%), appearing therefore particularly effective to prevent complications due to myocardial ischemia.

Atrial arrhythmias in adults with congenital heart disease.

BACKGROUND: Atrial arrhythmias increase disease burden in the general adult population. Adults with congenital heart lesions constitute a rapidly growing group of patients with cardiovascular disease. We hypothesized that atrial arrhythmias increase with age and impair health outcomes in this population. METHODS AND RESULTS: We conducted a population-based analysis of prevalence, lifetime risk, mortality, and morbidity associated with atrial arrhythmias in adults with congenital heart disease from l983 to 2005. In 38 428 adults with congenital heart disease in 2005, 5812 had atrial arrhythmias. Overall, the 20-year risk of developing atrial arrhythmia was 7% in a 20-year-old subject and 38% in a 50-year-old subject. More than 50% of patients with severe congenital heart disease reaching age 18 years developed atrial arrhythmias by age 65 years. In patients with congenital heart disease, the hazard ratio of any adverse event in those with atrial arrhythmias compared with those without was 2.50 (95% confidence interval, 2.38 to 2.62; P<0.0001), with a near 50% increase in mortality (hazard ratio, 1.47; 95% confidence interval, 1.37 to 1.58; P<0.001), more than double the risk of morbidity (stroke or heart failure) (hazard ratio, 2.21; 95% confidence interval, 2.07 to 2.36; P<0.001), and 3 times the risk of cardiac interventions (hazard ratio, 3.00; 95% confidence interval, 2.81 to 3.20; P<0.001). CONCLUSIONS: Atrial arrhythmias occurred in 15% of adults with congenital heart disease. The lifetime incidence increased steadily with age and was associated with a doubling of the risk of adverse events. An increase in resource allocation should be anticipated to deal with this increasing burden.

Ubiquitin- and ubiquitin-like proteins-conjugating enzymes (E2s) in breast cancer.

Breast cancer is the most common malignancy in women and a significant cause of morbidity and mortality. Sub-types of breast cancer defined by the expression of steroid hormones and Her2/Neu oncogene have distinct prognosis and undergo different therapies. Besides differing in their phenotype, sub-types of breast cancer display various molecular lesions that participate in their pathogenesis. BRCA1 is one of the common hereditary cancer predisposition genes and encodes for an ubiquitin ligase. Ubiquitin ligases or E3 enzymes participate together with ubiquitin activating enzyme and ubiquitin conjugating enzymes in the attachment of ubiquitin (ubiquitination) in target proteins. Ubiquitination is a post-translational modification regulating multiple cell functions. It also plays important roles in carcinogenesis in general and in breast carcinogenesis in particular. Ubiquitin conjugating enzymes are a central component of the ubiquitination machinery and are often perturbed in breast cancer. This paper will discuss ubiquitin and ubiquitin-like proteins conjugating enzymes participating in breast cancer pathogenesis, their relationships with other proteins of the ubiquitination machinery and their role in phenotype of breast cancer sub-types.

The Epidemiological Impact of Antimeningococcal B Vaccination in Cuba

The incidence of invasive meningococcal disease (IMD) before (1984-1988) and after (1989-1994), a nationwide intervention with VA-MENGOC-BC vaccination started in 1989, was compared. The prevaccination period incidence density (ID> 8.8/ 105 year-person) was higher than the postvaccination ID (ID< 6.5/ 105 year-person). The percentage proportional differences from the start to the end of each period of ID in the vaccinal period was higher (87%) than the prevaccinal (37%) with significant differences among vaccinated groups (< 25 years old). A break-point (Chow test) was confirmed by the decrease in the ID between 1989 and 1990 in children under 1 year old, 5-9, 10-14, 15-19 and 50-54 years. Comparison of ID using maps showed a decrease in IMD in all municipalities during the postvaccination period. These findings support the epidemiological impact of VA-MENGOC-BC vaccination in the reduction of IMD morbidity.

Epidemiology of hookworm infection in Itagua, Paraguay: a cross sectional study

A cross-sectional study in Itagua, Paraguay tested 192 people for the presence, intensity and species of hookworm infection. Fifty-nine percent of these individuals were found to be infected. Intensity of infection was determined on 92% of infected individuals by quantitative egg counts. The high intensity hookworm infections, which cause the greatest morbidity, were clustered between the ages of five and 14 years. No differences were seen between genders. The species of hookworm was determined for parasites reared from 72% of infected individuals. Both Necator americanus and Ancylostoma duodenale were identified, although the former species predominated. We conclude that hookworm infection continues to be a public health problem in Paraguay, particularly among children and adolescents who suffer from high intensity infections. A. duodenale continues to persist in the Western Hemisphere and has not been completely displaced by N. americanus.