Comparative Study of a Real-Time PCR Assay Targeting senX3-regX3 versus Other Molecular Strategies Commonly Used in the Diagnosis of Tuberculosis.

BACKGROUND Nucleic acid amplification tests are increasingly used for the rapid diagnosis of tuberculosis. We undertook a comparative study of the efficiency and diagnostic yield of a real-time PCR senX3-regX3 based assay versus the classical IS6110 target and the new commercial methods. METHODS This single-blind prospective comparative study included 145 consecutive samples: 76 from patients with culture-confirmed tuberculosis (86.8% pulmonary and 13.2% extrapulmonary tuberculosis: 48.7% smear-positive and 51.3% smear-negative) and 69 control samples (24 from patients diagnosed with non-tuberculous mycobacteria infections and 45 from patients with suspected tuberculosis which was eventually ruled out). All samples were tested by two CE-marked assays (Xpert®MTB/RIF and AnyplexTM plus MTB/NTM) and two in-house assays targeting senX3-regX3 and the IS6110 gene. RESULTS The detection limit ranged from 1.00E+01 fg for Anyplex, senX3-regX3 and IS6110 to 1.00E+04 fg for Xpert. All three Xpert, senX3-regX3 and IS6110 assays detected all 37 smear-positive cases. Conversely, Anyplex was positive in 34 (91.9%) smear-positive cases. In patients with smear-negative tuberculosis, differences were observed between the assays; Xpert detected 22 (56.41%) of the 39 smear-negative samples, Anyplex 24 (61.53%), senX3-regX3 28 (71.79%) and IS6110 35 (89.74%). Xpert and senX3-regX3 were negative in all control samples; however, the false positive rate was 8.7% and 13% for Anyplex and IS6110, respectively. The overall sensitivity was 77.6%, 85.7%, 77.3% and 94.7% and the specificity was 100%, 100%, 90.8% and 87.0% for the Xpert, senX3-regX3, Anyplex and IS6110 assays, respectively. CONCLUSION Real-time PCR assays targeting IS6110 lack the desired specificity. The Xpert MTB/RIF and in-house senX3-regX3 assays are both sensitive and specific for the detection of MTBC in both pulmonary and extrapulmonary samples. Therefore, the real time PCR senX3-regX3 based assay could be a useful and complementary tool in the diagnosis of tuberculosis.

Thyroid metastasis as initial presentation of clear cell renal carcinoma.

INTRODUCTION Metastatic tumors account for 1.4-2.5% of thyroid malignancies. About 25-30% of patients with clear cell renal carcinoma (CCRC) have distant metastasis at the time of diagnosis, being the thyroid gland a rare localization [5%]. PRESENTATION OF THE CASE A 62-year woman who underwent a cervical ultrasonography and a PAAF biopsy reporting atypical follicular proliferation with a few intranuclear vacuoles "suggestive" of thyroid papillary cancer in the context of a multinodular goiter was reported. A total thyroidectomy was performed and the histology of a clear cell renal carcinoma (CCRC) was described in four nodules of the thyroid gland. A CT scan was performed and a renal giant right tumor was found. The patient underwent an eventful radical right nephrectomy and the diagnosis of CCRC was confirmed. DISCUSSION Thyroid metastasis (TM) from CCRC are usually apparent in a metachronic context during the follow-up of a treated primary (even many years after) but may sometimes be present at the same time than the primary renal tumor. Our case is exceptional because the TM was the first evidence of the CCRC, which was subsequently diagnosed and treated. CONCLUSION The possibility of finding of an incidental metastatic tumor in the thyroid gland from a previous unknown and non-diganosed primary (as CCRC in our case was) is rare and account only for less than 1% of malignancies. Nonetheless, the thyroid gland is a frequent site of metastasis and the presence of "de novo" thyroid nodules in oncologic patients must be always considered and studied.

Management of hepatitis B virus infection after liver transplantation.

Chronic hepatitis B virus (HBV) infection is responsible for up to 30% of cases of liver cirrhosis and up to 53% of cases of hepatocellular carcinoma. Liver transplantation (LT) is the best therapeutic option for patients with end-stage liver failure caused by HBV. The success of transplantation, though, depends on receiving prophylactic treatment against post-transplant viral reactivation. In the absence of prophylaxis, liver transplantation due to chronic hepatitis B (CHB) is associated with high rates of viral recurrence and poor survival. The introduction of treatment with hepatitis B immunoglobulins (HBIG) during the 1990s and later the incorporation of oral antiviral drugs have improved the prognosis of these patients. Thus, LT for CHB is now a universally accepted option, with an estimated 5 years survival of around 85% vs the 45% survival seen prior to the introduction of HBIG. The combination of lamivudine plus HBIG has for many years been the most widely used prophylactic regimen. However, with the appearance of new more potent oral antiviral agents associated with less resistance (e.g., entecavir and tenofovir) for the treatment of CHB, new prophylactic strategies are being designed, either in combination with HBIG or alone as a monotherapy. These advances have allowed for more personalized prophylaxis based on the individual risk profile of a given patient. In addition, the small pool of donors has required the use of anti-HBc-positive donors (with the resulting possibility of transmitting HBV from these organs), which has been made possible by suitable prophylactic regimens.

Brachial artery peak velocity variation to predict fluid responsiveness in mechanically ventilated patients

INTRODUCTION Although several parameters have been proposed to predict the hemodynamic response to fluid expansion in critically ill patients, most of them are invasive or require the use of special monitoring devices. The aim of this study is to determine whether noninvasive evaluation of respiratory variation of brachial artery peak velocity flow measured using Doppler ultrasound could predict fluid responsiveness in mechanically ventilated patients. METHODS We conducted a prospective clinical research in a 17-bed multidisciplinary ICU and included 38 mechanically ventilated patients for whom fluid administration was planned due to the presence of acute circulatory failure. Volume expansion (VE) was performed with 500 mL of a synthetic colloid. Patients were classified as responders if stroke volume index (SVi) increased >or= 15% after VE. The respiratory variation in Vpeakbrach (DeltaVpeakbrach) was calculated as the difference between maximum and minimum values of Vpeakbrach over a single respiratory cycle, divided by the mean of the two values and expressed as a percentage. Radial arterial pressure variation (DeltaPPrad) and stroke volume variation measured using the FloTrac/Vigileo system (DeltaSVVigileo), were also calculated. RESULTS VE increased SVi by >or= 15% in 19 patients (responders). At baseline, DeltaVpeakbrach, DeltaPPrad and DeltaSVVigileo were significantly higher in responder than nonresponder patients [14 vs 8%; 18 vs. 5%; 13 vs 8%; P < 0.0001, respectively). A DeltaVpeakbrach value >10% predicted fluid responsiveness with a sensitivity of 74% and a specificity of 95%. A DeltaPPrad value >10% and a DeltaSVVigileo >11% predicted volume responsiveness with a sensitivity of 95% and 79%, and a specificity of 95% and 89%, respectively. CONCLUSIONS Respiratory variations in brachial artery peak velocity could be a feasible tool for the noninvasive assessment of fluid responsiveness in patients with mechanical ventilatory support and acute circulatory failure. TRIAL REGISTRATION ClinicalTrials.gov ID: NCT00890071.

Social inequalities and mortality in Europe-results from a large multi-national cohort

BACKGROUND Socio-economic inequalities in mortality are observed at the country level in both North America and Europe. The purpose of this work is to investigate the contribution of specific risk factors to social inequalities in cause-specific mortality using a large multi-country cohort of Europeans. METHODS A total of 3,456,689 person/years follow-up of the European Prospective Investigation into Cancer and Nutrition (EPIC) was analysed. Educational level of subjects coming from 9 European countries was recorded as proxy for socio-economic status (SES). Cox proportional hazard model's with a step-wise inclusion of explanatory variables were used to explore the association between SES and mortality; a Relative Index of Inequality (RII) was calculated as measure of relative inequality. RESULTS Total mortality among men with the highest education level is reduced by 43% compared to men with the lowest (HR 0.57, 95% C.I. 0.52-0.61); among women by 29% (HR 0.71, 95% C.I. 0.64-0.78). The risk reduction was attenuated by 7% in men and 3% in women by the introduction of smoking and to a lesser extent (2% in men and 3% in women) by introducing body mass index and additional explanatory variables (alcohol consumption, leisure physical activity, fruit and vegetable intake) (3% in men and 5% in women). Social inequalities were highly statistically significant for all causes of death examined in men. In women, social inequalities were less strong, but statistically significant for all causes of death except for cancer-related mortality and injuries. DISCUSSION In this European study, substantial social inequalities in mortality among European men and women which cannot be fully explained away by accounting for known common risk factors for chronic diseases are reported.

Modern diagnosis and treatment of diseases of children; a treatise on the medical and surgical diseases of infancy and childhood, with special emphasis upon clinical diagnosis and modern therpeutics.

Mode of access: Internet.

Health-related quality of life in patients with Chagas disease: a review of the evidence

Chagas disease (ChD), a neglected tropical disease caused by infection with the parasite Trypanosoma cruzi (T. cruzi), remains a serious public health issue in Latin America and is an emerging disease in several non-endemic countries, where knowledge of the condition and experience with its clinical management are limited. Regionally, the disease is the major cause of disability secondary to tropical diseases in young adults. Health-related quality of life (HRQoL) impairment is common in patients with ChD, especially in those with Chagas dilated cardiomyopathy, the most severe manifestation of the disease, which frequently leads to heart failure. The aim of this review was to conduct a literature search for studies that have evaluated the determining factors of HRQoL in ChD patients. We included cross-sectional, case-control, cohort, and experimental studies, as well as clinical trials that evaluated the HRQoL in ChD patients aged 18 to 60 years and are presenting an explicit description of statistical analysis. Using a combination of keywords based on Descriptors in Health Sciences (DeCS) and Medical Subject Headings (MeSH) for searches in PubMed and the Scientific Electronic Library Online (SciELO), 148 studies were found. After exclusions, 12 studies were selected for analysis. Three main findings were extracted from these studies: 1) cardiac involvement is associated with a worse HRQoL in ChD patients; 2) HRQoL is associated with the patients' functional capacity; and 3) simple and inexpensive therapeutic measures are effective for improving HRQoL in ChD patients. Hence, ChD patients' functional capacity, the effectiveness of non-surgical conservative treatment, and cardiac involvement are important determining factors for the HRQoL in ChD patients.

Consumption and portion sizes of tree nuts, peanuts and seeds in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohorts from 10 European countries

Tree nuts, peanuts and seeds are nutrient dense foods whose intake has been shown to be associated with reduced risk of some chronic diseases. They are regularly consumed in European diets either as whole, in spreads or from hidden sources (e.g. commercial products). However, little is known about their intake profiles or differences in consumption between European countries or geographic regions. The objective of this study was to analyse the population mean intake and average portion sizes in subjects reporting intake of nuts and seeds consumed as whole, derived from hidden sources or from spreads. Data was obtained from standardised 24-hour dietary recalls collected from 36 994 subjects in 10 different countries that are part of the European Prospective Investigation into Cancer and Nutrition (EPIC). Overall, for nuts and seeds consumed as whole, the percentage of subjects reporting intake on the day of the recall was: tree nuts = 4. 4%, peanuts = 2.3 % and seeds = 1.3 %. The data show a clear northern (Sweden: mean intake = 0.15 g/d, average portion size = 15.1 g/d) to southern (Spain: mean intake = 2.99 g/d, average portion size = 34.7 g/d) European gradient of whole tree nut intake. The three most popular tree nuts were walnuts, almonds and hazelnuts, respectively. In general, tree nuts were more widely consumed than peanuts or seeds. In subjects reporting intake, men consumed a significantly higher average portion size of tree nuts (28.5 v. 23.1 g/d, P<0.01) and peanuts (46.1 v. 35.1 g/d, P<0.01) per day than women. These data may be useful in devising research initiatives and health policy strategies based on the intake of this food group.

Surgical menopause increases salt sensitivity of blood pressure

Salt sensitivity of blood pressure is associated with an elevated risk of developing hypertension (HTN) and is an independent risk factor for cardiovascular disease. The prevalence of HTN increases after menopause. The aim of this study was to investigate prospectively whether the loss of ovarian hormones increases the occurrence of salt sensitivity among healthy premenopausal women. We enrolled 40 normotensive, nondiabetic women (age 47.2+/-3.5), undergoing hysterectomy-oophorectomy for nonneoplastic processes and not on hormone replacement, to determine the effect of changes in sodium intake on blood pressure the day before and subsequently 4 months after surgical menopause. Salt loading was achieved using a 2-L normal saline infusion and salt depletion produced by 40 mg of intravenous furosemide. A decrease >10 mm Hg in systolic blood pressure between salt loading and salt depletion was used to define salt sensitivity. Before and after menopause, salt-sensitive women exhibited higher waist/hip and waist/thigh ratios (P<0.01). Although all of the women remained normotensive, the prevalence of salt sensitivity was significantly higher after surgical menopause (21 women; 52.5%) than before (9 women; 22.5%; P=0.01), because 12 (38.7%) salt-resistant women developed salt sensitivity after menopause. In summary, we demonstrated that the prevalence of salt sensitivity doubled as early as 4 months after surgical menopause, without an associated increase in blood pressure. Epidemiological studies indicate that development of HTN may not occur until 5 to 10 years after menopause. The loss of ovarian hormones may unmask a population of women prone to salt sensitivity who, with aging, would be at higher risk for the subsequent development of HTN and cardiovascular disease.

Do socioeconomic inequalities in mortality vary between different Spanish cities? a pooled cross-sectional analysis.

BACKGROUND The relationship between deprivation and mortality in urban settings is well established. This relationship has been found for several causes of death in Spanish cities in independent analyses (the MEDEA project). However, no joint analysis which pools the strength of this relationship across several cities has ever been undertaken. Such an analysis would determine, if appropriate, a joint relationship by linking the associations found. METHODS A pooled cross-sectional analysis of the data from the MEDEA project has been carried out for each of the causes of death studied. Specifically, a meta-analysis has been carried out to pool the relative risks in eleven Spanish cities. Different deprivation-mortality relationships across the cities are considered in the analysis (fixed and random effects models). The size of the cities is also considered as a possible factor explaining differences between cities. RESULTS Twenty studies have been carried out for different combinations of sex and causes of death. For nine of them (men: prostate cancer, diabetes, mental illnesses, Alzheimer's disease, cerebrovascular disease; women: diabetes, mental illnesses, respiratory diseases, cirrhosis) no differences were found between cities in the effect of deprivation on mortality; in four cases (men: respiratory diseases, all causes of mortality; women: breast cancer, Alzheimer's disease) differences not associated with the size of the city have been determined; in two cases (men: cirrhosis; women: lung cancer) differences strictly linked to the size of the city have been determined, and in five cases (men: lung cancer, ischaemic heart disease; women: ischaemic heart disease, cerebrovascular diseases, all causes of mortality) both kinds of differences have been found. Except for lung cancer in women, every significant relationship between deprivation and mortality goes in the same direction: deprivation increases mortality. Variability in the relative risks across cities was found for general mortality for both sexes. CONCLUSIONS This study provides a general overview of the relationship between deprivation and mortality for a sample of large Spanish cities combined. This joint study allows the exploration of and, if appropriate, the quantification of the variability in that relationship for the set of cities considered.

El proyecto EMECAS: protocolo del estudio multicéntrico en España de los efectos a corto plazo de la contaminación atmosférica sobre la salud.

The EMECAM Project demonstrated the short-term effect of air pollution on the death rate in 14 cities in Spain throughout the 1990-1995 period. The Spanish Multicentre Study on Health Effects of Air Pollution (EMECAS) is broadening these objectives by incorporating more recent data, information on hospital disease admissions and totaling 16 Spanish cities. This is an ecological time series study in which the response variables are the daily deaths and the emergency hospitalizations due to circulatory system diseases and respiratory diseases among the residents in each city. Pollutants analyses: suspended particles, SO2, NO2, CO and O3. Control variables: meteorological, calendar, seasonality and influenza trend and incidence. Statistical analysis: estimate of the association in each city by means of the construction of generalized additive Poisson regression models and metanalysis for obtaining combined estimators. The EMECAS Project began with the creation of three working groups (Exposure, Epidemiology and Analysis Methodology) which defined the protocol. The average levels of pollutants were below those established under the current regulations for sulfur dioxide, carbon monoxide and ozone. The NO2 and PM10 values were around those established under the regulations (40 mg/m3). This is the first study of the relationship between air pollution and disease rate among one group of Spanish cities. The pollution levels studied are moderate for some pollutants, although for others, especially NO2 and particles, these levels could entail a problem with regard to complying with the regulations in force.

Trends in self-reported past alcoholic beverage consumption and ethanol intake from 1950 to 1995 observed in eight European countries participating in the European Investigation into Cancer and Nutrition (EPIC).

OBJECTIVE To describe the trends of self-reported past consumption of alcoholic beverages and ethanol intake from 1950 to 1995 within the European Prospective Investigation into Cancer and Nutrition (EPIC). DESIGN Data on consumption of beer/cider, wine and liqueur/spirits were obtained retrospectively at age 20, 30 and 40 years to calculate average consumption and ethanol intake for the time periods 1950-1975 (at age 20), 1960-1985 (at age 30) and 1970-1995 (at age 40). Regression analysis was conducted with the time period data to assess trends in past alcoholic beverage consumption and ethanol intake with time. SETTING The EPIC project. SUBJECTS In total, 392 064 EPIC participants (275 249 women and 116 815 men) from 21 study centres in eight European countries. RESULTS Generally, increases in beer/cider consumption were observed for most EPIC centres for 1950-1975, 1960-1985 and 1970-1995. Trends in wine consumption differed according to geographical location: downward trends with time were observed for men in southern European EPIC centres, upward trends for those in middle/northern European study centres. For women, similar but less pronounced trends were observed. Because wine consumption was the major contributor to ethanol intake for both men and women in most study centres, time trends for ethanol intake showed a similar geographical pattern to that of wine consumption. CONCLUSION The different trends in alcoholic beverage consumption and ethanol intake suggest that information depicting lifetime history of ethanol intake should be included in analyses of the relationship between ethanol and chronic diseases, particularly in multi-centre studies such as EPIC.

Team Effectiveness in Patient Health Management: An Overview of Reviews

Background: The desire to improve the quality of health care for an aging population with multiple chronic diseases is fostering a rapid growth in inter-professional team care, supported by health professionals, governments, businesses and public institutions. However, the weight of evidence measuring the impact of team care on patient and health system outcomes has not, heretofore, been clear. To address this deficiency, we evaluated published evidence for the clinical effectiveness of team care within a chronic disease management context in a systematic overview. Methods: A search strategy was built for Medline using medical subject headings and other relevant keywords. After testing for perform- ance, the search strategy was adapted to other databases (Cinhal, Cochrane, Embase, PsychInfo) using their specific descriptors. The searches were limited to reviews published between 1996 and 2011, in English and French languages. The results were analyzed by the number of studies favouring team intervention, based on the direction of effect and statistical significance for all reported outcomes. Results: Sixteen systematic and 7 narrative reviews were included. Diseases most frequently targeted were depression, followed by heart failure, diabetes and mental disorders. Effective- ness outcome measures most commonly used were clinical endpoints, resource utilization (e.g., emergency room visits, hospital admissions), costs, quality of life and medication adherence. Briefly, while improved clinical and resource utilization endpoints were commonly reported as positive outcomes, mixed directional results were often found among costs, medication adherence, mortality and patient satisfaction outcomes. Conclusions: We conclude that, although suggestive of some specific benefits, the overall weight of evidence for team care efficacy remains equivocal. Further studies that examine the causal interactions between multidisciplinary team care and clinical and economic outcomes of disease management are needed to more accurately assess its net program efficacy and population effectiveness.

Fine-tuning the space, time, and host distribution of mycobacteria in wildlife.

Background. We describe the diversity of two kinds of mycobacteria isolates, environmental mycobacteria and Mycobacterium bovis collected from wild boar, fallow deer, red deer and cattle in Doñana National Park (DNP, Spain), analyzing their association with temporal, spatial and environmental factors. Results. High diversity of environmental mycobacteria species and M. bovis typing patterns (TPs) were found. When assessing the factors underlying the presence of the most common types of both environmental mycobacteria and M. bovis TPs in DNP, we evidenced (i) host species differences in the occurrence, (ii) spatial structuration and (iii) differences in the degree of spatial association of specific types between host species. Co-infection of a single host by two M. bovis TPs occurred in all three wild ungulate species. In wild boar and red deer, isolation of one group of mycobacteria occurred more frequently in individuals not infected by the other group. While only three TPs were detected in wildlife between 1998 and 2003, up to 8 different ones were found during 2006-2007. The opposite was observed in cattle. Belonging to an M. bovis-infected social group was a significant risk factor for mycobacterial infection in red deer and wild boar, but not for fallow deer. M. bovis TPs were usually found closer to water marshland than MOTT. Conclusions. The diversity of mycobacteria described herein is indicative of multiple introduction events and a complex multi-host and multi-pathogen epidemiology in DNP. Significant changes in the mycobacterial isolate community may have taken place, even in a short time period (1998 to 2007). Aspects of host social organization should be taken into account in wildlife epidemiology. Wildlife in DNP is frequently exposed to different species of non-tuberculous, environmental mycobacteria, which could interact with the immune response to pathogenic mycobacteria, although the effects are unknown. This research highlights the suitability of molecular typing for surveys at small spatial and temporal scales.

Concentrations of resveratrol and derivatives in foods and estimation of dietary intake in a Spanish population: European Prospective Investigation into Cancer and Nutrition (EPIC)-Spain cohort

Resveratrol has been shown to have beneficial effects on diseases related to oxidant and/or inflammatory processes and extends the lifespan of simple organisms including rodents. The objective of the present study was to estimate the dietary intake of resveratrol and piceid (R&P) present in foods, and to identify the principal dietary sources of these compounds in the Spanish adult population. For this purpose, a food composition database (FCDB) of R&P in Spanish foods was compiled. The study included 40 685 subjects aged 35–64 years from northern and southern regions of Spain who were included in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Spain cohort. Usual food intake was assessed by personal interviews using a computerised version of a validated diet history method. An FCDB with 160 items was compiled. The estimated median and mean of R&P intake were 100 and 933 μg/d respectively. Approximately, 32 % of the population did not consume R&P. The most abundant of the four stilbenes studied was trans-piceid (53·6 %), followed by trans-resveratrol (20·9 %), cis-piceid (19·3 %) and cis-resveratrol (6·2 %). The most important source of R&P was wines (98·4 %) and grape and grape juices (1·6 %), whereas peanuts, pistachios and berries contributed to less than 0·01 %. For this reason the pattern of intake of R&P was similar to the wine pattern. This is the first time that R&P intake has been estimated in a Mediterranean country.