Chemotherapy in advanced biliary tract carcinoma: a pooled analysis of clinical trials

Owing to the lack of randomised controlled trials no standard of chemotherapy exists in the treatment of advanced biliary tract carcinoma. 5-fluorouracil or gemcitabine is recommended based on small and predominately phase II trials. The aim of this analysis was to analyse existing trials, even small and nonrandomised, and identify superior regimens. Chemotherapy trials published in English from 1985 to July 2006 were analysed as well as ASCO abstracts from 1999 to 2006. Response rate (RR=CR+PR), tumour control rate (TCR=CR+PR+SD), time to tumour progression (TTP), overall survival (OS), and toxicity were analysed. One hundred and four trials comprising 112 trial arms and 2810 patients, thereof 634 responders and 1368 patients with tumour control were analysed. Pooled RR and TCR were 22.6 and 57.3%, respectively. Significant correlations of RR and TCR with survival times were found. Subgroup analysis showed superior RRs for gallbladder carcinoma (GBC) compared with cholangiocarcinoma, but shorter OS for GBC. Furthermore, superior RRs and TCRs of gemcitabine and platinum containing regimens were found with highest RRs and TCRs in the combination subgroup. Based on published results of predominately phase II trials, gemcitabine combined with platinum compounds represents the provisional standard of chemotherapy in advanced biliary tract cancer, unless a new evidence-based standard has been defined

A prevalence survey of every-day activities in pregnancy

<p>Abstract</p> <p>Background</p> <p>Research into the effects of common activities during pregnancy is sparse and often contradictory. To examine whether common activities are an acute trigger of pregnancy complications the prevalence of these activities are necessary to determine sample size estimates. The aim of this study is to ascertain the prevalence of selected activities in any seven day period during pregnancy.</p> <p>Methods</p> <p>The study was conducted in the antenatal clinic of a teaching hospital with tertiary obstetric and neonatal care in Sydney, Australia between August 2008 and April 2009. Women who were at least 20 weeks pregnant and able to read English completed a questionnaire to assess whether they had performed a list of activities in the seven days prior to survey completion. Results were analysed using frequency tabulations, contingency table analyses and chi square tests.</p> <p>Results</p> <p>A total of 766 surveys were completed, 29 surveys were excluded as the women completing them were less than 20 weeks pregnant, while 161 women completed the survey more than once. Ninety seven per cent of women completed the survey when approached for the first time, while 87% completed the survey when approached a subsequent time. In the week prior to completing the survey 82.6% of women had consumed a caffeinated beverage, 42.1% had had sexual intercourse, 32.7% had lifted something over 12 kilograms, 21.4% had consumed alcohol and 6.4% had performed vigorous exercise. The weekly prevalence of heavy lifting was higher for multiparous women compared to nulliparous women.</p> <p>Conclusions</p> <p>The results of this study can be used to inform future research into activities as acute triggers of pregnancy complications.</p

Using principal component analysis to develop a single-parameter screening tool for metabolic syndrome

Abstract Background Metabolic syndrome (MS) is an important current public health problem faced worldwide. To prevent an "epidemic" of this syndrome, it is important to develop an easy single-parameter screening technique (such as waist circumference (WC) determination recommended by the International Diabetes Federation). Previous studies proved that age is a chief factor corresponding to central obesity. We intended to present a new index based on the linear combination of body mass index, and age, which could enhance the area under the receiver operating characteristic curves (AUCs) for assessing the risk of MS. Methods The labour law of the Association of Labor Standard Law, Taiwan, states that employers and employees are respectively obligated to offer and receive routine health examination periodically. Secondary data analysis and subject's biomarkers among five high-tech factories were used in this study between 2007 and 2008 in northern Taiwan. The subjects included 4712 males and 4196 females. The first principal component score (FPCS) and equal-weighted average (EWA) were determined by statistical analysis. Results Most of the metabolic and clinical characteristics were significantly higher in males than in females, except high-density lipoprotein cholesterol level. The older group (>45 years) had significantly lower values for height and high-density lipoprotein cholesterol level than the younger group. The AUCs of FPCS and EWA were significantly larger than those of WC and waist-to-height ratio. The low specificities of EWA and FPCS were compensated for by their substantially high sensitivities. FPCS ≥ 0.914 (15.4%) and EWA ≥ 8.8 (6.3%) were found to be the most prevalent cut off points in males and females, respectively. Conclusions The Bureau of Health Promotion, Department of Health, Taiwan, had recommended the use of WC ≥ 90 cm for males and ≥ 80 cm for females as singular criteria for the determination of central obesity instead of multiple parameters. The present investigation suggests that FPCS or EWA is a good predictor of MS among the Taiwanese. However, the use of FPCS is not computationally feasible in practice. Therefore, we suggest that EWA be used in clinical practice as a simple parameter for the identification of those at risk of MS.</p

Patterning in Birthweight in India: Analysis of Maternal Recall and Health Card Data

National data on birthweight from birth certificates or medical records are not available in India. The third Indian National Family Health Survey included data on birthweight of children obtained from health cards and maternal recall. This study aims to describe the population that these data represent and compares the birthweight obtained from health cards with maternal recall data in terms of its socioeconomic patterning and as a risk factor for childhood growth failure.The analytic sample consisted of children aged 0 to 59 months with birthweight data obtained from health cards (n = 3227) and maternal recall (n = 16,787). The difference between the card sample and the maternal recall sample in the distribution across household wealth, parental education, caste, religion, gender, and urban residence was compared using multilevel models. We also assessed the ability of birthweight to predict growth failure in infancy and childhood in the two groups. The survey contains birthweight data from a majority of household wealth categories (>5% in every category for recall), both genders, all age groups, all caste groups, all religion groups, and urban and rural dwellers. However, children from the lowest quintile of household wealth were under-represented (4.73% in card and 8.62% in recall samples). Comparison of data across health cards and maternal recall revealed similar social patterning of low birthweight and ability of birthweight to predict growth failure later in life. Children were less likely to be born with low birthweight if they had mothers with over 12 years of education compared to 1-5 years of education with relative risk (RR) of 0.79 (95% confidence interval [CI]: 0.52, 1.2) in the card sample and 0.70 (95% CI: 0.59, 0.84) in the recall sample. A 100 gram difference in a child's birthweight was associated with a decreased likelihood of underweight in both the card (RR: 0.95; 95% CI: 0.94, 0.96) and recall (RR: 0.96; 95% CI: 0.96, 0.97) samples.Our results suggest that in the absence of other sources, the data on birthweight in the third Indian National Family Health Survey is valuable for epidemiologic research

Análisis de la evolución del PIB agrí­cola en paí­ses de América Latina

La investigación tuvo como objetivo clasificar   los distintos paí­ses latinoamericanos a partir del denominado PIB Agrí­cola. Se obtuvo, para 20 paí­ses: Argentina, Bolivia, Brasil,  Chile, Colombia, Costa Rica, Cuba, República Dominicana, Ecuador, Guatemala, Honduras, Haití­, Jamaica, México, Nicaragua, Panamá, Perú, El Salvador, Uruguay y Venezuela la variación del % que representa la Agricultura, de acuerdo con las  divisiones 1-5 de la CIIU, que incluye: silvicultura, caza, pesca, cultivo de cosechas y la crí­a de animales. El procesamiento estadí­stico de estos datos, permitió agrupar a los paí­ses   en 5 clústeres. La mayor parte de los paí­ses 8, se agrupa en un clúster que   mantiene el indicador en un rango de 4.72 a 8.56 y una desviación estándar de 1.43. Este grupo corresponde a paí­ses que aunque en comparación con 1990 reducen el PIB Agrí­cola,   mantienen a partir del 2010 este indicador   relativamente estable. La agrupación obtenida  sugiere investigaciones futuras que puedan determinar la posible relación entre este indicador y por ejemplo,   el porcentaje de empleos en la agricultura.Se obtuvo un importante conjunto de referencias sobre las temáticas: desarrollo rural, tributación agrí­cola y PIB Agrí­cola recopiladas como Base de Datos que se pone a disposición de otros investigadores interesados en estos temas

Alphacoronaviruses in New World Bats: Prevalence, Persistence, Phylogeny, and Potential for Interaction with Humans

Bats are reservoirs for many different coronaviruses (CoVs) as well as many other important zoonotic viruses. We sampled feces and/or anal swabs of 1,044 insectivorous bats of 2 families and 17 species from 21 different locations within Colorado from 2007 to 2009. We detected alphacoronavirus RNA in bats of 4 species: big brown bats (Eptesicus fuscus), 10% prevalence; long-legged bats (Myotis volans), 8% prevalence; little brown bats (Myotis lucifugus), 3% prevalence; and western long-eared bats (Myotis evotis), 2% prevalence. Overall, juvenile bats were twice as likely to be positive for CoV RNA as adult bats. At two of the rural sampling sites, CoV RNAs were detected in big brown and long-legged bats during the three sequential summers of this study. CoV RNA was detected in big brown bats in all five of the urban maternity roosts sampled throughout each of the periods tested. Individually tagged big brown bats that were positive for CoV RNA and later sampled again all became CoV RNA negative. Nucleotide sequences in the RdRp gene fell into 3 main clusters, all distinct from those of Old World bats. Similar nucleotide sequences were found in amplicons from gene 1b and the spike gene in both a big-brown and a long-legged bat, indicating that a CoV may be capable of infecting bats of different genera. These data suggest that ongoing evolution of CoVs in bats creates the possibility of a continued threat for emergence into hosts of other species. Alphacoronavirus RNA was detected at a high prevalence in big brown bats in roosts in close proximity to human habitations (10%) and known to have direct contact with people (19%), suggesting that significant potential opportunities exist for cross-species transmission of these viruses. Further CoV surveillance studies in bats throughout the Americas are warranted

Ethnic and sex differences in the incidence of hospitalized acute myocardial infarction: British Columbia, Canada 1995-2002

<p>Abstract</p> <p>Background</p> <p>As populations in Western countries continue to change in their ethnic composition, there is a need for regular surveillance of diseases that have previously shown some health disparities. Earlier data have already demonstrated high rates of cardiovascular mortality among South Asians and relatively lower rates among people of Chinese descent. The aim of this study was to describe the differences in the incidence of hospitalized acute myocardial infarction (AMI) among the three largest ethnic groups in British Columbia (BC), Canada.</p> <p>Methods</p> <p>Using hospital administrative data, we identified all patients with incident AMI in BC between April 1, 1995, and March 31, 2002. Census data from 2001 provided the denominator for the entire BC population. Ethnicity was determined using validated surname analysis and applied to the census and hospital administrative datasets. Direct age standardization was used to compare incidence rates.</p> <p>Results</p> <p>A total of 34,848 AMI cases were identified. Among men, South Asians had the highest age standardized rate of AMI hospitalization at 4.97/1000 population/year, followed by Whites at 3.29, and then Chinese at 0.98. Young South Asian men, in particular, showed incidence rates that were double that of young Whites and ten times that of young Chinese men. South Asian women also had the highest age-standardized rate of AMI hospitalization at 2.35/1000 population/year, followed by White women (1.53) and Chinese women (0.49).</p> <p>Conclusions</p> <p>South Asians continue to have a higher incidence of hospitalized AMI while incidence rates among Chinese remain low. Ethnic differences are most notable among younger men.</p

Leishmania donovani: Immunostimulatory Cellular Responses of Membrane and Soluble Protein Fractions of Splenic Amastigotes in Cured Patient and Hamsters

Visceral leishmaniasis (VL), caused by the intracellular parasite Leishmania donovani, L. chagasi and L. infantum is characterized by defective cell-mediated immunity (CMI) and is usually fatal if not treated properly. An estimated 350 million people worldwide are at risk of acquiring infection with Leishmania parasites with approximately 500,000 cases of VL being reported each year. In the absence of an efficient and cost-effective antileishmanial drug, development of an appropriate long-lasting vaccine against VL is the need of the day. In VL, the development of a CMI, capable of mounting Th1-type of immune responses, play an important role as it correlate with recovery from and resistance to disease. Resolution of infection results in lifelong immunity against the disease which indicates towards the feasibility of a vaccine against the disease. Most of the vaccination studies in Leishmaniasis have been focused on promastigote- an infective stage of parasite with less exploration of pathogenic amastigote form, due to the cumbersome process of its purified isolation. In the present study, we have isolated and purified splenic amastigotes of L. donovani, following the traditional protocol with slight modification. These were fractionated into five membranous and soluble subfractions each i.e MAF1-5 and SAF1-5 and were subjected for evaluation of their ability to induce cellular responses. Out of five sub-fractions from each of membrane and soluble, only four viz. MAF2, MAF3, SAF2 and SAF3 were observed to stimulate remarkable lymphoproliferative, IFN-γ, IL-12 responses and Nitric Oxide production, in Leishmania-infected cured/exposed patients and hamsters. Results suggest the presence of Th-1 type immunostimulatory molecules in these sub-fractions which may further be exploited for developing a successful subunit vaccine from the less explored pathogenic stage against VL

Quantitative Proteomic and Interaction Network Analysis of Cisplatin Resistance in HeLa Cells

Cisplatin along with other platinum based drugs are some of the most widely used chemotherapeutic agents. However drug resistance is a major problem for the successful chemotherapeutic treatment of cancer. Current evidence suggests that drug resistance is a multifactorial problem due to changes in the expression levels and activity of a wide number of proteins. A majority of the studies to date have quantified mRNA levels between drug resistant and drug sensitive cell lines. Unfortunately mRNA levels do not always correlate with protein expression levels due to post-transcriptional changes in protein abundance. Therefore global quantitative proteomics screens are needed to identify the protein targets that are differentially expressed in drug resistant cell lines. Here we employ a quantitative proteomics technique using stable isotope labeling with amino acids in cell culture (SILAC) coupled with mass spectrometry to quantify changes in protein levels between cisplatin resistant (HeLa/CDDP) and sensitive HeLa cells in an unbiased fashion. A total of 856 proteins were identified and quantified, with 374 displaying significantly altered expression levels between the cell lines. Expression level data was then integrated with a network of protein-protein interactions, and biological pathways to obtain a systems level view of proteome changes which occur with cisplatin resistance. Several of these proteins have been previously implicated in resistance towards platinum-based and other drugs, while many represent new potential markers or therapeutic targets

A cross-sectional investigation of regional patterns of diet and cardio-metabolic risk in India

<p>Abstract</p> <p>Background</p> <p>The role of diet in India's rapidly progressing chronic disease epidemic is unclear; moreover, diet may vary considerably across North-South regions.</p> <p>Methods</p> <p>The India Health Study was a multicenter study of men and women aged 35-69, who provided diet, lifestyle, and medical histories, as well as blood pressure, fasting blood, urine, and anthropometric measurements. In each region (Delhi, n = 824; Mumbai, n = 743; Trivandrum, n = 2,247), we identified two dietary patterns with factor analysis. In multiple logistic regression models adjusted for age, gender, education, income, marital status, religion, physical activity, tobacco, alcohol, and total energy intake, we investigated associations between regional dietary patterns and abdominal adiposity, hypertension, diabetes, and dyslipidemia.</p> <p>Results</p> <p>Across the regions, more than 80% of the participants met the criteria for abdominal adiposity and 10 to 28% of participants were considered diabetic. In Delhi, the "fruit and dairy" dietary pattern was positively associated with abdominal adiposity [highest versus lowest tertile, multivariate-adjusted OR and 95% CI: 2.32 (1.03-5.23); P_trend= 0.008] and hypertension [2.20 (1.47-3.31); P_trend< 0.0001]. In Trivandrum, the "pulses and rice" pattern was inversely related to diabetes [0.70 (0.51-0.95); P_trend= 0.03] and the "snacks and sweets" pattern was positively associated with abdominal adiposity [2.05 (1.34-3.14); P_trend= 0.03]. In Mumbai, the "fruit and vegetable" pattern was inversely associated with hypertension [0.63 (0.40-0.99); P_trend= 0.05] and the "snack and meat" pattern appeared to be positively associated with abdominal adiposity.</p> <p>Conclusions</p> <p>Cardio-metabolic risk factors were highly prevalent in this population. Across all regions, we found little evidence of a Westernized diet; however, dietary patterns characterized by animal products, fried snacks, or sweets appeared to be positively associated with abdominal adiposity. Conversely, more traditional diets in the Southern regions were inversely related to diabetes and hypertension. Continued investigation of diet, as well as other environmental and biological factors, will be needed to better understand the risk profile in this population and potential means of prevention.</p