Cell-Associated HIV-1 RNA in Blood as Indicator of Virus Load in Lymph Nodes

We have developed sensitive assays for viremia and cell-associated human immunodeficiency virus type 1 (HIV-1) RNA and DNA to assess the predictive value of virological parameters determined in blood for virus load in lymph nodes (LNs). Eighteen patients were included; 13 received stavudine/didanosine/hydroxyurea and 5 stavudine/didanosine, and all had viremia 3 months. At the time of LN biopsy (median, 10 months), the median viremia was 2.09 log copies/mL (range, <0.70-3.34). Cell-associated HIV-1 RNA and DNA were detectable in blood and LNs of all patients. The median cell-associated RNA and DNA were 2.16 log copies/106 cells and 2.60 log copies/106 cells in blood versus 4.31 log RNA copies/106 cells and 3.26 log DNA copies/106 cells in LNs. Regression analysis shows that, in treated patients with sustained low viremia, cell-associated RNA and DNA in blood are better predictors of virus load in LNs than viremi

Impact of Treatment with Human Immunodeficiency Virus (HIV) Protease Inhibitors on Hepatitis C Viremia in Patients Coinfected with HIV

The impact of human immunodeficiency virus (HIV) protease inhibitors on hepatitis C (HCV) viremia was assessed in 19 patients infected with both HIV and HCV. HIV and HCV RNA levels were measured before and during treatment with protease inhibitors. before treatment, mean levels of HCV RNA were 5.3 log for HCV RNA and 5.0 log for HIV RNA. CD4 lymphocyte counts were 63/mm3. after 6 weeks of treatment, a mean reduction of 2.1 log10 in HIV RNA (P < .001) and a mean (±SE) increase of 73 (±21) CD4 and 296 (±70) CD8 cells were observed (P < .05). In contrast, both HCV viremia (+0.4 log ± 0.1) and alanine aminotransferase increased (P < .04). HCV RNA levels returned to baseline after 17 and 32 weeks of treatment. Thus, potent anti-HIV regimens with protease inhibitors may temporarily worsen HCV status despite improvement of HIV parameter

Predictors and Implications of Early Clinical Stability in Patients Hospitalized for Moderately Severe Community-Acquired Pneumonia.

Assessment of early response to treatment is crucial for the management of community-acquired pneumonia (CAP). To describe the predictors and the outcomes of early clinical stability. We did a secondary analysis of a multicentre randomized controlled trial on CAP treatment in which 580 patients hospitalized for moderately severe CAP were included. The association between demographic, clinical and biological variables available at inclusion and early clinical stability (stabilization of vital signs within 72 hours with predetermined cut-offs) was assessed by multivariate logistic regression. The association between early clinical stability and mortality, severe adverse events, and length of stay was also tested. Younger age (OR 0.98, 95% CI 0.96-0.99), lower platelet count (OR per 10 G/L increment 0.96, 95% CI 0.94-0.98), lower respiratory rate (OR 0.94, 95% CI 0.90-0.97), absence of hypoxemia (OR 0.58, 95% CI 0.40-0.85), lower numbers of co-morbid conditions (OR 0.82, 95% CI 0.69-0.98) and signs or symptoms (OR 0.78, 95% CI 0.68-0.90) were significantly associated with early clinical stability. Patients with early clinical stability had lower 90-days mortality (3.4% vs. 11.9%, p&lt;0.001), fewer admissions to the intensive care unit (2.7% vs. 8.0%, p = 0.005) and a shorter length of stay (6.0 days, IQR 4.0-10.0 vs. 10.0 days, IQR 7.0-15.0, p&lt;0.001). Patients with younger age, less co-morbidity, fewer signs or symptoms, less respiratory compromise, and a lower platelet count are more likely to reach early clinical stability. Patients without early clinical stability have a worse prognosis and warrant close scrutiny

β-Lactam Monotherapy vs β-Lactam-Macrolide Combination Treatment in Moderately Severe Community-Acquired Pneumonia: A Randomized Noninferiority Trial.

IMPORTANCE: The clinical benefit of adding a macrolide to a β-lactam for empirical treatment of moderately severe community-acquired pneumonia remains controversial. OBJECTIVE: To test noninferiority of a β-lactam alone compared with a β-lactam and macrolide combination in moderately severe community-acquired pneumonia. DESIGN, SETTING, AND PARTICIPANTS: Open-label, multicenter, noninferiority, randomized trial conducted from January 13, 2009, through January 31, 2013, in 580 immunocompetent adult patients hospitalized in 6 acute care hospitals in Switzerland for moderately severe community-acquired pneumonia. Follow-up extended to 90 days. Outcome assessors were masked to treatment allocation. INTERVENTIONS: Patients were treated with a β-lactam and a macrolide (combination arm) or with a β-lactam alone (monotherapy arm). Legionella pneumophila infection was systematically searched and treated by addition of a macrolide to the monotherapy arm. MAIN OUTCOMES AND MEASURES: Proportion of patients not reaching clinical stability (heart rate &lt;100/min, systolic blood pressure &gt;90 mm Hg, temperature &lt;38.0°C, respiratory rate &lt;24/min, and oxygen saturation &gt;90% on room air) at day 7. RESULTS: After 7 days of treatment, 120 of 291 patients (41.2%) in the monotherapy arm vs 97 of 289 (33.6%) in the combination arm had not reached clinical stability (7.6% difference, P = .07). The upper limit of the 1-sided 90% CI was 13.0%, exceeding the predefined noninferiority boundary of 8%. Patients infected with atypical pathogens (hazard ratio [HR], 0.33; 95% CI, 0.13-0.85) or with Pneumonia Severity Index (PSI) category IV pneumonia (HR, 0.81; 95% CI, 0.59-1.10) were less likely to reach clinical stability with monotherapy, whereas patients not infected with atypical pathogens (HR, 0.99; 95% CI, 0.80-1.22) or with PSI category I to III pneumonia (HR, 1.06; 95% CI, 0.82-1.36) had equivalent outcomes in the 2 arms. There were more 30-day readmissions in the monotherapy arm (7.9% vs 3.1%, P = .01). Mortality, intensive care unit admission, complications, length of stay, and recurrence of pneumonia within 90 days did not differ between the 2 arms. CONCLUSIONS AND RELEVANCE: We did not find noninferiority of β-lactam monotherapy in patients hospitalized for moderately severe community-acquired pneumonia. Patients infected with atypical pathogens or with PSI category IV pneumonia had delayed clinical stability with monotherapy. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00818610

Opiophobia in Emergency Department Healthcare Providers: A Survey in Western Switzerland.

Opiophobia contributes to oligoanalgesia in the emergency department (ED), but its definition varies, and its association to healthcare providers' personality traits has been scantly explored. Our purpose was to study the different definitions of opiophobia and their association with two personality traits of doctors and nurses working in EDs, namely the stress from uncertainty and risk-taking. We used three online questionnaires: the 'Attitude Towards Morphine Use' Score (ATMS), the Stress From Uncertainty Scale (SUS) and the Risk-Taking Scale (RTS). Doctors and nurses from nine hospital EDs in francophone Switzerland were invited to participate. The ATMS score was analyzed according to demographic characteristics, SUS, and RTS. The response rate was 56%, with 57% of respondents being nurses and 63% women. Doctors, less experienced and non-indigenous participants had a significantly higher ATMS (all p ≤ 0.01). The main contributors of the ATMS were the fear of side effects and of addiction. In multivariate analysis, being a doctor, less experience and non-indigenous status were predictive of the ATMS; each point of the SUS increased the ATMS by 0.24 point. The fear of side effects and of addiction were the major contributors of opiophobia among ED healthcare providers; opiophobia was also associated with their personality traits

Reliability of the revised Swiss Emergency Triage Scale: a computer simulation study.

The Swiss Emergency Triage Scale (SETS) is a four-level emergency scale that previously showed moderate reliability and high rates of undertriage due to a lack of standardization. It was revised to better standardize the measurement and interpretation of vital signs during the triage process. The aim of this study was to explore the inter-rater and test-retest reliability, and the rate of correct triage of the revised SETS. Thirty clinical scenarios were evaluated twice at a 3-month interval using an interactive computerized triage simulator by 58 triage nurses at an urban teaching emergency department admitting 60 000 patients a year. Inter-rater and test-retest reliabilities were determined using κ statistics. Triage decisions were compared with a gold standard attributed by an expert panel. Rates of correct triage, undertriage, and overtriage were computed. A logistic regression model was used to identify the predictors of correct triage. A total of 3387 triage situations were analyzed. Inter-rater reliability showed substantial agreement [mean κ: 0.68; 95% confidence interval (CI): 0.60-0.78] and test-retest almost perfect agreement (mean κ: 0.86; 95% CI: 0.84-0.88). The rate of correct triage was 84.1%, and rates of undertriage and overtriage were 7.2 and 8.7%, respectively. Vital sign measurement was an independent predictor of correct triage (odds ratios for correct triage: 1.29 for each additional vital sign measured, 95% CI: 1.20-1.39). The revised SETS incorporating standardized vital sign measurement and interpretation during the triage process resulted in high reliability and low rates of mistriage

Quel rôle peut-on imputer aux banques à charte canadiennes dans la transmission des chocs monétaires des années quatre-vingt?

Cette recherche s’inscrit dans la foulée de nombreux travaux entrepris suite aux publications de Bernanke et Blinder (1988, 1992) ayant remis à l’avant-plan le rôle joué par le système bancaire dans la transmission de la politique monétaire. Nous proposons d’examiner la dynamique inhérente à certains postes du bilan des banques à charte canadiennes suite aux mouvement des principaux taux d’intérêt, habituellement jugés révélateurs des conditions monétaires du moment. Pour ce faire, nous avons recours à un modèle VAR hebdomadaire comportant à la fois, des éléments de l’actif et du passif des banques ainsi que les taux de rendement associés à divers instruments financiers. Cependant, dans le but de bien encadrer cette analyse, nous développons un modèle formel du comportement d’une banque où les seuls changements aux postes de son bilan suite aux mouvements de taux d’intérêt sont dictés par des ajustements de portefeuille visant à tirer avantage des écarts se creusant entre ceux-ci. Ce modèle théorique est soumis aux variations de taux d’intérêt issues du modèle empirique VAR. Les mouvements observés aux postes du bilan de cette banque « témoin » fournissent un guide utile permettant d’interpréter de façon éclairée les résultats empiriques obtenus. À cet égard, l’exercice proposé montre qu’il est possible d’établir un parallèle assez étroit entre l’évolution des postes du bilan de la banque hypothétique et celle captée par le modèle VAR et ainsi apporte un certain support à l’approche traditionnelle sur le rôle joué par les banques dans la transmission des chocs monétaires.This paper can be seen as a contribution to a growing literature initiated by Bernanke and Blinder (1988, 1992) which have examined the role played by the banking system in the transmission of monetary policy. We propose to study the dynamic behaviour of the balance sheet of Canadian chartered banks following a shock to some key interest rates which are good indicators of the prevailing monetary conditions. More specifically, we estimate a weekly VAR model which comprises key asset and liabilities elements as well as rates of return on major financial instruments. However, to guide this empirical inquiry, we set up a model of a representative bank which adjusts its balance sheet elements according to the interest rate spreads arising in the financial markets. This theoretical model is then subjected to the same interest rate shocks than those imposed on the VAR model: the adjustments observed in this laboratory will prove quite useful to assess the significance of the empirical results uncovered by the VAR model. Overall, we find that both approaches give rise to quite similar dynamic responses which tends to support the traditional role of the banking sector in the transmission of monetary policy

Macroevolutionary Patterns in the Aphidini Aphids (Hemiptera: Aphididae): Diversification, Host Association, and Biogeographic Origins

, the most diverse genus in the family. We used a combined dataset of one nuclear and four mitochondrial DNA regions. A molecular dating approach, calibrated with fossil records, was used to estimate divergence times of these taxa.Most generic divergences in Aphidini occurred in the Middle Tertiary, and species-level divergences occurred between the Middle and Late Tertiary. The ancestral state of host use for Aphidini was equivocal with respect to three states: monoecy on trees, heteroecy, and monoecy on grasses. The ancestral state of Rhopalosiphina likely included both heteroecy and monoecy, whereas that of Aphidina was most likely monoecy. The divergence times of aphid lineages at the generic or subgeneric levels are close to those of their primary hosts. The species-level divergences in aphids are consistent with the diversification of the secondary hosts, as a few examples suggest. The biogeographic origin of Aphidini as a whole was equivocal, but the major lineages within Aphidina likely separated into Nearctic, Western Palearctic, and Eastern Palearctic regions.Most generic divergences in Aphidini occurred in the Middle Tertiary when primary hosts, mainly in the Rosaceae, were diverging, whereas species-level divergences were contemporaneous with diversification of the secondary hosts such as Poaceae in the Middle to Late Tertiary. Our results suggest that evolution of host alternation within Aphidini may have occurred during the Middle Tertiary (Oligocene) when the secondary hosts emerged

The Drosophila melanogaster host model

The deleterious and sometimes fatal outcomes of bacterial infectious diseases are the net result of the interactions between the pathogen and the host, and the genetically tractable fruit fly, Drosophila melanogaster, has emerged as a valuable tool for modeling the pathogen–host interactions of a wide variety of bacteria. These studies have revealed that there is a remarkable conservation of bacterial pathogenesis and host defence mechanisms between higher host organisms and Drosophila. This review presents an in-depth discussion of the Drosophila immune response, the Drosophila killing model, and the use of the model to examine bacterial–host interactions. The recent introduction of the Drosophila model into the oral microbiology field is discussed, specifically the use of the model to examine Porphyromonas gingivalis–host interactions, and finally the potential uses of this powerful model system to further elucidate oral bacterial-host interactions are addressed