The inter-rater reliability of the Pulmonary Embolism Severity Index.

The Pulmonary Embolism Severity Index (PESI) is a validated clinical prognostic model for patients with acute pulmonary embolism (PE). Our goal was to assess the PESI's inter-rater reliability in patients diagnosed with PE. We prospectively identified consecutive patients diagnosed with PE in the emergency department of a Swiss teaching hospital. For all patients, resident and attending physician raters independently collected the 11 PESI variables. The raters then calculated the PESI total point score and classified patients into one of five PESI risk classes (I-V) and as low (risk classes I/II) versus higher-risk (risk classes III-V). We examined the inter-rater reliability for each of the 11 PESI variables, the PESI total point score, assignment to each of the five PESI risk classes, and classification of patients as low versus higher-risk using kappa (κ) and intra-class correlation coefficients (ICC). Among 48 consecutive patients with an objective diagnosis of PE, reliability coefficients between resident and attending physician raters were > 0.60 for 10 of the 11 variables comprising the PESI. The inter-rater reliability for the PESI total point score (ICC: 0.89, 95% CI: 0.81-0.94), PESI risk class assignment (κ: 0.81, 95% CI: 0.66-0.94), and the classification of patients as low versus higher-risk (κ: 0.92, 95% CI: 0.72-0.98) was near perfect. Our results demonstrate the high reproducibility of the PESI, supporting the use of the PESI for risk stratification of patients with PE.

The category 'natural' in the discourse of couples who used medically assisted procreation

As a constantly evolving set of complex biotechnologies, medically assisted procreation (MAP) jeopardises a category that seems to be taken for granted: that of 'natural'. What is 'natural' or not when MAP is used to procreate? What are the boundaries between a 'natural' and a 'non-natural' fertilisation? Drawing upon a dialogical approach to language and cognition, our study examined the semantic field of the category 'natural' as expressed in interviews between a psychiatrist and seven couples who resorted to MAP and had to decide whether to keep their frozen pre-embryonic cells (zygotes) for further procreation or to allow them be destroyed. We examined how these couples evoked the category 'natural' and showed that in their argumentation, the category 'natural' encompassed a wide variety of phenomena, which shifted the boundaries between the 'natural' and 'non-natural'. In so doing, the couples 'renaturalised' MAP, normalized it, moved the boundaries between what is legitimate or not, and showed their accountability. Hence, reference to the category 'natural' seemed to act both as an argumentative and a psychological resource in the elaboration of the person's experience in resorting to MAP.

Maladies inflammatoires de l'intestin [Main therapeutic advances in IBD in 2008]

A coimmunosuppression with azathioprine or methotrexate in addition to infliximab does not improve the therapeutic efficacy in Crohn's disease but increase the risks of infectious complications and neoplasia.

Therapeutic drug monitoring of imatinib: Bayesian and alternative methods to predict trough levels

Background: The imatinib trough plasma concentration (C(min)) correlates with clinical response in cancer patients. Therapeutic drug monitoring (TDM) of plasma C(min) is therefore suggested. In practice, however, blood sampling for TDM is often not performed at trough. The corresponding measurement is thus only remotely informative about C(min) exposure. Objectives: The objectives of this study were to improve the interpretation of randomly measured concentrations by using a Bayesian approach for the prediction of C(min), incorporating correlation between pharmacokinetic parameters, and to compare the predictive performance of this method with alternative approaches, by comparing predictions with actual measured trough levels, and with predictions obtained by a reference method, respectively. Methods: A Bayesian maximum a posteriori (MAP) estimation method accounting for correlation (MAP-ρ) between pharmacokinetic parameters was developed on the basis of a population pharmacokinetic model, which was validated on external data. Thirty-one paired random and trough levels, observed in gastrointestinal stromal tumour patients, were then used for the evaluation of the Bayesian MAP-ρ method: individual C(min) predictions, derived from single random observations, were compared with actual measured trough levels for assessment of predictive performance (accuracy and precision). The method was also compared with alternative approaches: classical Bayesian MAP estimation assuming uncorrelated pharmacokinetic parameters, linear extrapolation along the typical elimination constant of imatinib, and non-linear mixed-effects modelling (NONMEM) first-order conditional estimation (FOCE) with interaction. Predictions of all methods were finally compared with 'best-possible' predictions obtained by a reference method (NONMEM FOCE, using both random and trough observations for individual C(min) prediction). Results: The developed Bayesian MAP-ρ method accounting for correlation between pharmacokinetic parameters allowed non-biased prediction of imatinib C(min) with a precision of ±30.7%. This predictive performance was similar for the alternative methods that were applied. The range of relative prediction errors was, however, smallest for the Bayesian MAP-ρ method and largest for the linear extrapolation method. When compared with the reference method, predictive performance was comparable for all methods. The time interval between random and trough sampling did not influence the precision of Bayesian MAP-ρ predictions. Conclusion: Clinical interpretation of randomly measured imatinib plasma concentrations can be assisted by Bayesian TDM. Classical Bayesian MAP estimation can be applied even without consideration of the correlation between pharmacokinetic parameters. Individual C(min) predictions are expected to vary less through Bayesian TDM than linear extrapolation. Bayesian TDM could be developed in the future for other targeted anticancer drugs and for the prediction of other pharmacokinetic parameters that have been correlated with clinical outcomes.

Alcohol-related and hepatocellular cancer deaths by country of birth in England and Wales: analysis of mortality and census data.

BACKGROUND: The incidence of and mortality from alcohol-related conditions, liver disease and hepatocellular cancer (HCC) are increasing in the UK. We compared mortality rates by country of birth to explore potential inequalities and inform clinical and preventive care. DESIGN: Analysis of mortality for people aged 20 years and over using the 2001 Census data and death data from 1999 and 2001-2003. SETTING: England and Wales. MAIN OUTCOME MEASURES: Standardized mortality ratios (SMRs) for alcohol-related deaths and HCC. RESULTS: Mortality from alcohol-related deaths (23 502 deaths) was particularly high for people born in Ireland (SMR for men [M]: 236, 95% confidence interval [CI]: 219-254; SMR for women [F]: 212, 95% CI: 191-235) and Scotland (SMR-M: 187, CI: 173-213; SMR-F 182, CI: 163-205) and men born in India (SMR-M: 161, CI: 144-181). Low alcohol-related mortality was found in women born in other countries and men born in Bangladesh, Middle East, West Africa, Pakistan, China and Hong Kong, and the West Indies. Similar mortality patterns were observed by country of birth for alcoholic liver disease and other liver diseases. Mortality from HCC (8266 deaths) was particularly high for people born in Bangladesh (SMR-M: 523, CI: 380-701; SMR-F: 319, CI: 146-605), China and Hong Kong (SMR-M: 492, CI: 168-667; SMR-F: 323, CI: 184-524), West Africa (SMR-M: 440, CI, 308-609; SMR-F: 319, CI: 165-557) and Pakistan (SMR-M: 216, CI: 113-287; SMR-F: 215, CI: 133-319). CONCLUSIONS: These findings show persistent differences in mortality by country of birth for both alcohol-related and HCC deaths and have important clinical and public health implications. New policy, research and practical action are required to address these differences.This resource was contributed by The National Documentation Centre on Drug Use.

Gastric bypass in morbid obese patients is associated with reduction in adipose tissue inflammation via N-oleoylethanolamide (OEA)-mediated pathways.

Paradoxically, morbid obesity was suggested to protect from cardiovascular co-morbidities as compared to overweight/obese patients. We hypothesise that this paradox could be inferred to modulation of the "endocannabinoid" system on systemic and subcutaneous adipose tissue (SAT) inflammation. We designed a translational project including clinical and in vitro studies at Geneva University Hospital. Morbid obese subjects (n=11) were submitted to gastric bypass surgery (GBS) and followed up for one year (post-GBS). Insulin resistance and circulating and SAT levels of endocannabinoids, adipocytokines and CC chemokines were assessed pre- and post-GBS and compared to a control group of normal and overweight subjects (CTL) (n=20). In vitro cultures with 3T3-L1 adipocytes were used to validate findings from clinical results. Morbid obese subjects had baseline lower insulin sensitivity and higher hs-CRP, leptin, CCL5 and anandamide (AEA) levels as compared to CTL. GBS induced a massive weight and fat mass loss, improved insulin sensitivity and lipid profile, decreased C-reactive protein, leptin, and CCL2 levels. In SAT, increased expression of resistin, CCL2, CCL5 and tumour necrosis factor and reduced MGLL were shown in morbid obese patients pre-GBS when compared to CTL. GBS increased all endocannabinoids and reduced adipocytokines and CC chemokines. In morbid obese SAT, inverse correlations independent of body mass index were shown between palmitoylethanolamide (PEA) and N-oleoylethanolamide (OEA) levels and inflammatory molecules. In vitro, OEA inhibited CCL2 secretion from adipocytes via ERK1/2 activation. In conclusion, GBS was associated with relevant clinical, metabolic and inflammatory improvements, increasing endocannabinoid levels in SAT. OEA directly reduced CCL2 secretion via ERK1/2 activation in adipocytes.

Aspects of peridomiciliary ecotopes in rural areas of Northeastern Brazil associated to triatomine (Hemiptera, Reduviidae) infestation, vectors of Chagas disease

Artificial ecotopes of 121 peridomiciliary environments in four rural localities in the state of Ceará, Brazil, were studied and the type of material of the ecotopes was identified as triatomine infestation. Two thousand two hundred and four Triatoma brasiliensis Neiva, 340 Triatoma pseudomaculata Corrêa and Espínola, 121 Rhodnius nasutus Stall, and 5 Panstrongylus lutzi (Neiva and Pinto) were captured. Out of the 323 ecotopes found (X =2.0 ± 1.8 per dwelling) such as pigpens, henhouses, corrals, perches, dovecotes, piles of roofing tiles, bricks, wood, and straw 30.3% were infested by triatomines in all different developmental stages, including eggs. A substantial number of triatomines were found in perches, however the largest infestation took place in roofing materials used in the construction of goat/sheep corrals, henhouses, and pigpens, where 98% of them were captured: 1372 triatomines were located in the roofing tile covers, 285 in the straw, 187 in the perches, 77 in the coverings of roofing tiles and straw, and 13 in the straw and wood. Among all the different pile of materials, roofing tiles were the most infested (50%) followed by bricks (38.9%) and woods (36.1%). T. brasiliensis colonized mainly brick piles (chi2=16.539; p < 0.05) and roofing tiles (chi2=5,090.58; p < 0.05); T. pseudomaculata preferred wood perches (chi2= 472.39; p < 0.05) and woodpiles (chi2=126.0 p < 0.05), and R. nasutus was principally found in roofing straw (chi2=384.43; p < 0.05). These findings suggest that triatomines tend to colonize peridomiciliary ecotopes similar to their original habitats.

Medical students' skills and needs for training in breaking bad news.

This study assessed medical students' perception of individual vs. group training in breaking bad news (BBN) and explored training needs in BBN. Master-level students (N = 124) were randomised to group training (GT)-where only one or two students per group conducted a simulated patient (SP) interview, which was discussed collectively with the faculty-or individual training (IT)-where each student conducted an SP interview, which was discussed during individual supervision. Training evaluation was based on questionnaires, and the videotaped interviews were rated using the Roter Interaction Analysis System. Students were globally satisfied with the training. Still, there were noticeable differences between students performing an interview (GT/IT) and students observing interviews (GT). The analysis of the interviews showed significant differences according to scenarios and to gender. Active involvement through SP interviews seems required for students to feel able to reach training objectives. The evaluation of communication skills, revealing a baseline heterogeneity, supports individualised training.

Omics meets hypothesis-driven research. Partnership for innovative discoveries in vascular biology and angiogenesis.

The emergence of omics technologies allowing the global analysis of a given biological or molecular system, rather than the study of its individual components, has revolutionized biomedical research, including cardiovascular medicine research in the past decade. These developments raised the prospect that classical, hypothesis-driven, single gene-based approaches may soon become obsolete. The experience accumulated so far, however, indicates that omic technologies only represent tools similar to those classically used by scientists in the past and nowadays, to make hypothesis and build models, with the main difference that they generate large amounts of unbiased information. Thus, omics and classical hypothesis-driven research are rather complementary approaches with the potential to effectively synergize to boost research in many fields, including cardiovascular medicine. In this article we discuss some general aspects of omics approaches, and review contributions in three areas of vascular biology, thrombosis and haemostasis, atherosclerosis and angiogenesis, in which omics approaches have already been applied (vasculomics).

Effect of embryo culture media on birthweight and length in singleton term infants after IVF-ICSI.

QUESTIONS UNDER STUDY: To investigate if two distinct, commercially available embryo culture media have a different effect on birthweight and length of singleton term infants conceived after IVF-ICSI. METHODS: University hospital based cohort study. Between 1 January 2000 and 31 December 2004, patients conceiving through IVF-ICSI at the University Hospital, Lausanne have been allocated to two distinct embryo culture media. Only term singleton pregnancies were analysed (n = 525). Data analysis was performed according to two commercially available culture media: Vitrolife (n = 352) versus Cook (n = 173). Analysis was performed through linear regression adjusted for confounders. Media were considered equivalent if the 95% confidence interval lay between -150 g/+150 g. RESULTS: Length, gestational age and distribution of birthweight percentiles did not differ between groups (for both genders). Analysis of the whole cohort, adjusted for a subset of confounders, resulted in a statistically not different mean birthweight between the two groups (Vitrolife +37 g vs Cook, 95%CI: -46 g to 119 g) suggesting equivalence. Adjustment for an enlarged number of confounders in a subsample of patients (n = 258) also revealed no relevant mean birthweight difference of +71 g (95%CI: -45 g to 187 g) in favour of Vitrolife; however, lacking power to prove equivalence. CONCLUSIONS: Our data suggest that significant differences in birthweight due to these two distinct, commercially available embryo culture media are unlikely.

Population genetic structure of the dengue mosquito Aedes aegypti in Venezuela

The mosquito Aedes aegypti is the main vector of dengue in Venezuela. The genetic structure of this vector was investigated in 24 samples collected from eight geographic regions separated by up to 1160 km. We examined the distribution of a 359-basepair region of the NADH dehydrogenase subunit 4 mitochondrial gene among 1144 Ae. aegypti from eight collections. This gene was amplified by the polymerase chain reaction and tested for variation using single strand conformation polymorphism analysis. Seven haplotypes were detected throughout Venezuela and these were sorted into two clades. Significant differentiation was detected among collections and these were genetically isolated by distance.

Slime production and antibiotic susceptibility in staphylococci isolated from clinical samples

A total of 187 isolates from several clinical specimens were identified to species level as 129 Staphylococcus aureus strains and 58 coagulase-negative staphylococci (CNS) strains by the API Staph System (Biomerieux). Slime production was detected both by the conventional Christensen's method as well as by the Congo red agar method. Seventy-two strains of staphylococci isolates (38.5%) were found to be slime producers by Christensen's test tube method whereas 58 strains (31%) were slime positive with Congo red agar method. There was no statistically significant difference between the two methods for the detection of slime production (P > 0.05). Susceptibility of isolates against antimicrobial agents was tested by the disk diffusion method. Staphylococcal species had resistance to one or more antibiotics. Among the various antimicrobial agents, oxacillin (71.1%) and erythromycin (47.1%) showed higher resistance than most of the agents used against all isolates. Oxacillin resistant S. aureus (ORSA) and oxacillin resistant coagulase-negative staphylococci (ORCNS), 97 (75.2%) and 36 (62.1%) respectively were frequently observed in strains isolated from clinical materials. Among the ORSA strains, two strains were resistant to vancomycin. Moreover, 96 (74.4%) of 129 S. aureus strains were positive for blactamase enzyme. However, 78 (81.25%) of 96 b-lactamase positive S. aureus strains were b-lactamase positive ORSA isolates, but none of them had vancomycin resistance.

Causes of health expenditure growth : the predominance of changes in medical practices over population ageing

On the basis of French individual data, this paper compares the effects of demographic change, changes in morbidity and changes in practices on the growth in health expenditures that occurred between 1992 and 2000. Micro simulations show that the rise in expenditures due to ageing is relatively small and that the impact of changes in practices is times larger. Furthermore, changes in morbidity induce savings which more than offset the increase in spending due to population ageing. [Authors]

The significance of pre-existing minority Y181C mutations on virological failure of NNRTI-based, first-line antiretroviral therapy

Background: Reduced re'nal function has been reported with tenofovir disoproxil fumarate (TDF). It is not clear whether TDF co-administered with a boosted protease inhibitor (PI) leads to a greater decline in renal function than TDF co-administered with a non-nucleoside reverse transcriptase inhibitor (NNRTI).Methods: We selected ail antiretroviral therapy-naive patients in the Swiss HIV Cohort Study (SHCS) with calibrated or corrected serum creatinine measurements starting antiretroviral therapy with TDF and either efavirenz (EFV) or the ritonavir-boosted PIs, lopinavir (LPV/r) or atazanavir (ATV/r). As a measure of renal function, we used the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation to estimate the glomerular filtration rate (eGFR). We calculated the difference in eGFR over time between two therapies using a marginal model for repeated measures. In weighted analyses, observations were weighted by the product of their point of treatment and censoring weights to adjust for differences both in the sort of patients starting each therapy and in the sort of patients remaining on each therapy over time.Results: By March 2011, 940 patients with at least one creatinine measurement on a first therapy with either TDF and EFV (n=484), TDF and LPVlr (n=269) or TDF and ATV/r (n=187) had been followed for a median of 1. 7, 1.2 and 1.3 years, respectively. Table 1 shows the difference in average estimated GFR (eGFR) over time since starting cART for two marginal models. The first model was not adjusted for potential confounders; the second mode! used weights to adjust for confounders. The results suggest a greater decline in renal function during the first 6 months if TDF is used with a PI rather than with an NNRTI, but no further difference between these therapies after the first 6 months. TDF and ATV/r may lead to a greater decline in the first 6 months than TDF and LPVlr.Conclusions: TDF co-administered with a boosted PI leads to a greater de cline in renal function over the first 6 months of therapy than TDF co-administered with an NNRTI; this decline may be worse with ATV/r than with LPV/r.

Detection of diarrheagenic Escherichia coli from children with and without diarrhea in Salvador, Bahia, Brazil

We identified different diarrheagenic (DEC) Escherichia coli pathotypes isolated from 1,207 children with and without acute endemic diarrhea in Salvador, Bahia, Brazil collected as part of a case-control study. Since the identification of DEC cannot be based on only biochemical and culture criteria, we used a multiplex polymerase chain reaction developed by combining five specific primer pairs for Enteropathogenic Escherichia coli (EPEC), Shiga toxin-producing E. coli/ Enterohaemorrhagic E. coli (STEC/EHEC), Enterotoxigenic E. coli (ETEC) and Enteroaggregative E. coli (EAEC) to detect these pathotypes simultaneously in a single-step reaction. In order to distinguish typical and atypical EPEC strains, these were tested for the presence of EAF plasmid. The prevalence of diarrheagenic E. coli in this sample of a global case-control study was 25.4% (259 patients) and 18.7% (35 patients) in the diarrhea group (1,020 patients) and the control group (187 patients), respectively. The most frequently isolated pathotype was EAEC (10.7%), followed by atypical EPEC (9.4%), ETEC (3.7%), and STEC (0.6%). Typical EPEC was detected only in one sample. The prevalence of the pathotypes studied in children with diarrhea was not significantly different from that in children without diarrhea.