Do pediatricians manage influenza differently than internists?

<p>Abstract</p> <p>Background</p> <p>Little is known about how pediatricians or internists manage influenza symptoms. Recent guidelines on antiviral prescribing by the Centers for Disease Control and Prevention (CDC) make almost no distinction between adults and children. Our objective was to describe how pediatricians in two large academic medical institutions manage influenza and compare them to internists.</p> <p>Methods</p> <p>At the end of the 2003–4 influenza season, we conducted a cross sectional on-line survey of physician knowledge, attitudes and practices regarding rapid diagnostic testing and use of antiviral therapy for influenza at two large academic medical centers, one in Massachusetts and the other in Texas. We collected data on self-reported demographics, test use, prescribing practices, and beliefs about influenza and anti-influenza drugs.</p> <p>Results</p> <p>A total of 107 pediatricians and 103 internists completed the survey (response rate of 53%). Compared to internists, pediatricians were more likely to perform rapid testing (74% vs. 47%, p < 0.0001), to use amantadine (88% vs. 48%, p < 0.0001), to restrict their prescribing to high-risk patients (86% vs. 53%, p < 0.0001), and to believe that antiviral therapy could decrease mortality (38% vs. 22%, p = 0.01). Other beliefs about antiviral therapy did not differ statistically between the specialties. Internists were more likely to be unfamiliar with rapid testing or not to have it available.</p> <p>Conclusion</p> <p>Pediatricians and internists manage influenza differently. Evidence-based guidelines addressing the specific concerns of each group would be helpful.</p

Plasma folate levels are associated with the lipoprotein profile: a retrospective database analysis

BACKGROUND: Several studies demonstrated an association of homocysteine plasma levels and the plasma lipoprotein profile. This cross-sectional pilot study aimed at analyzing whether blood levels of the two important cofactors of homocysteine metabolism, folate and vitamin B12, coincide with the lipoprotein profile. METHODS: In a retrospective single center approach, we analyzed the laboratory database (2003-2006) of the University Hospital Bonn, Germany, including 1743 individuals, in whom vitamin B12, folate and at least one lipoprotein parameter had been determined by linear multilogistic regression. RESULTS: Higher folate serum levels were associated with lower serum levels of low density lipoprotein cholesterol (LDL-C; Beta = -0.164; p < 0.001), higher levels of high density lipoprotein cholesterol (HDL-C; Beta = 0.094; p = 0.021 for trend) and a lower LDL-C-C/HDL-C-ratio (Beta = -0.210; p < 0.001). Using ANOVA, we additionally compared the individuals of the highest with those of the lowest quartile of folate. Individuals of the highest folate quartile had higher levels of HDL-C (1.42 +/- 0.44 mmol/l vs. 1.26 +/- 0.47 mmol/l; p = 0.005), lower levels of LDL-C (3.21 +/- 1.04 mmol/l vs. 3.67 +/- 1.10 mmol/l; p = 0.001) and a lower LDL-C/HDL-C- ratio (2.47 +/- 1.18 vs. 3.77 +/- 5.29; p = 0.002). Vitamin B12 was not associated with the lipoprotein profile. CONCLUSION: In our study sample, high folate levels were associated with a favorable lipoprotein profile. A reconfirmation of these results in a different study population with a well defined status of health, diet and medication is warranted

Influenza Outbreak during Sydney World Youth Day 2008: The Utility of Laboratory Testing and Case Definitions on Mass Gathering Outbreak Containment

BACKGROUND:Influenza causes annual epidemics and often results in extensive outbreaks in closed communities. To minimize transmission, a range of interventions have been suggested. For these to be effective, an accurate and timely diagnosis of influenza is required. This is confirmed by a positive laboratory test result in an individual whose symptoms are consistent with a predefined clinical case definition. However, the utility of these clinical case definitions and laboratory testing in mass gathering outbreaks remains unknown. METHODS AND RESULTS:An influenza outbreak was identified during World Youth Day 2008 in Sydney. From the data collected on pilgrims presenting to a single clinic, a Markov model was developed and validated against the actual epidemic curve. Simulations were performed to examine the utility of different clinical case definitions and laboratory testing strategies for containment of influenza outbreaks. Clinical case definitions were found to have the greatest impact on averting further cases with no added benefit when combined with any laboratory test. Although nucleic acid testing (NAT) demonstrated higher utility than indirect immunofluorescence antigen or on-site point-of-care testing, this effect was lost when laboratory NAT turnaround times was included. The main benefit of laboratory confirmation was limited to identification of true influenza cases amenable to interventions such as antiviral therapy. CONCLUSIONS:Continuous re-evaluation of case definitions and laboratory testing strategies are essential for effective management of influenza outbreaks during mass gatherings

To Test or to Treat? An Analysis of Influenza Testing and Antiviral Treatment Strategies Using Economic Computer Modeling

BACKGROUND: Due to the unpredictable burden of pandemic influenza, the best strategy to manage testing, such as rapid or polymerase chain reaction (PCR), and antiviral medications for patients who present with influenza-like illness (ILI) is unknown.\ud \ud METHODOLOGY/PRINCIPAL FINDINGS: We developed a set of computer simulation models to evaluate the potential economic value of seven strategies under seasonal and pandemic influenza conditions: (1) using clinical judgment alone to guide antiviral use, (2) using PCR to determine whether to initiate antivirals, (3) using a rapid (point-of-care) test to determine antiviral use, (4) using a combination of a point-of-care test and clinical judgment, (5) using clinical judgment and confirming the diagnosis with PCR testing, (6) treating all with antivirals, and (7) not treating anyone with antivirals. For healthy younger adults (<65 years old) presenting with ILI in a seasonal influenza scenario, strategies were only cost-effective from the societal perspective. Clinical judgment, followed by PCR and point-of-care testing, was found to be cost-effective given a high influenza probability. Doubling hospitalization risk and mortality (representing either higher risk individuals or more virulent strains) made using clinical judgment to guide antiviral decision-making cost-effective, as well as PCR testing, point-of-care testing, and point-of-care testing used in conjunction with clinical judgment. For older adults (> or = 65 years old), in both seasonal and pandemic influenza scenarios, employing PCR was the most cost-effective option, with the closest competitor being clinical judgment (when judgment accuracy > or = 50%). Point-of-care testing plus clinical judgment was cost-effective with higher probabilities of influenza. Treating all symptomatic ILI patients with antivirals was cost-effective only in older adults.\ud \ud CONCLUSIONS/SIGNIFICANCE: Our study delineated the conditions under which different testing and antiviral strategies may be cost-effective, showing the importance of accuracy, as seen with PCR or highly sensitive clinical judgment.\ud \u

Vitamin C and asthma in children: modification of the effect by age, exposure to dampness and the severity of asthma

Retraction: Clinical and Translational Allergy 2012, 2:6BACKGROUND: We previously found a significant benefit of vitamin C supplementation in asthmatic children. PURPOSE: To test whether the effect of vitamin C on asthma is heterogeneous over the participant population. METHODS: Egyptian asthmatic children between 7 and 10 years of age (n = 60) were included in the cross-over trial. They were administered 0.2 grams per day of vitamin C and placebo for separate 6-week periods. The variation in the vitamin C effect on two clinically relevant outcomes was analyzed: the childhood asthma control test (C-ACT), which measures the severity of asthma symptoms (the scale ranges from 0 to 27 points, < 20 points indicating unsatisfactory asthma control), and FEV1. We used linear modeling to examine the variation of the vitamin C effect in the subgroups. RESULTS: The effect of vitamin C on the C-ACT was significantly modified by age and baseline C-ACT levels. In the children aged 7.0-8.2 years with a baseline C-ACT of 18 to 19 points, vitamin C increased the C-ACT score by 4.2 points (95% CI: 3.3-5.3); whereas in the children aged 8.3-10 years who had a baseline C-ACT of 14 to 15 points, vitamin C increased the C-ACT score by only 1.3 points (95% CI: 0.1-2.5). The effect of vitamin C on the FEV1 levels was significantly modified by age and exposure to dampness. In the children aged 7.0-8.2 years with no exposure to dampness, vitamin C increased the FEV1 level by 37% (95% CI: 34-40%), whereas in the children aged 8.3-10 years with exposure to dampness or mold in their bedroom more than one year prior to the study, vitamin C increased the FEV1 level by only 21% (95% CI: 18-25%). CONCLUSIONS: We found strong evidence that the effect of vitamin C on asthmatic children is heterogeneous. Further research is needed to confirm our findings and identify the groups of children who would receive the greatest benefit from vitamin C supplementation.Peer reviewe

Sequestration of free cholesterol in cell membranes by prions correlates with cytoplasmic phospholipase A2 activation

<p>Abstract</p> <p>Background</p> <p>The transmissible spongiform encephalopathies (TSEs), otherwise known as the prion diseases, occur following the conversion of the normal cellular prion protein (PrP^C) to an alternatively folded isoform (PrP^Sc). The accumulation of PrP^Scwithin the brain leads to neurodegeneration through an unidentified mechanism. Since many neurodegenerative disorders including prion, Parkinson's and Alzheimer's diseases may be modified by cholesterol synthesis inhibitors, the effects of prion infection on the cholesterol balance within neuronal cells were examined.</p> <p>Results</p> <p>We report the novel observation that prion infection altered the membrane composition and significantly increased total cholesterol levels in two neuronal cell lines (ScGT1 and ScN2a cells). There was a significant correlation between the concentration of free cholesterol in ScGT1 cells and the amounts of PrP^Sc. This increase was entirely a result of increased amounts of free cholesterol, as prion infection reduced the amounts of cholesterol esters in cells. These effects were reproduced in primary cortical neurons by the addition of partially purified PrP^Sc, but not by PrP^C. Crucially, the effects of prion infection were not a result of increased cholesterol synthesis. Stimulating cholesterol synthesis via the addition of mevalonate, or adding exogenous cholesterol, had the opposite effect to prion infection on the cholesterol balance. It did not affect the amounts of free cholesterol within neurons; rather, it significantly increased the amounts of cholesterol esters. Immunoprecipitation studies have shown that cytoplasmic phospholipase A₂(cPLA₂) co-precipitated with PrP^Scin ScGT1 cells. Furthermore, prion infection greatly increased both the phosphorylation of cPLA₂and prostaglandin E₂production.</p> <p>Conclusion</p> <p>Prion infection, or the addition of PrP^Sc, increased the free cholesterol content of cells, a process that could not be replicated by the stimulation of cholesterol synthesis. The presence of PrP^Scincreased solubilisation of free cholesterol in cell membranes and affected their function. It increased activation of the PLA₂pathway, previously implicated in PrP^Scformation and in PrP^Sc-mediated neurotoxicity. These observations suggest that the neuropathogenesis of prion diseases results from PrP^Scaltering cholesterol-sensitive processes. Furthermore, they raise the possibility that disturbances in membrane cholesterol are major triggering events in neurodegenerative diseases.</p

Trypanosomatid RACK1 Orthologs Show Functional Differences Associated with Translation Despite Similar Roles in Leishmania Pathogenesis

RACK1 proteins belong to the eukaryote WD40-repeat protein family and function as spatial regulators of multiple cellular events, including signaling pathways, the cell cycle and translation. For this latter role, structural and genetic studies indicate that RACK1 associates with the ribosome through two conserved positively charged amino acids in its first WD40 domain. Unlike RACK1s, including Trypanosoma brucei RACK1 (TbRACK1), only one of these two positively-charged residues is conserved in the first WD40 domain of the Leishmania major RACK1 ortholog, LACK. We compared virulence-attenuated LACK single copy (LACK/-) L. major, with L. major expressing either two LACK copies (LACK/LACK), or one copy each of LACK and TbRACK1 (LACK/TbRACK1), to evaluate the function of these structurally distinct RACK1 orthologs with respect to translation, viability at host temperatures and pathogenesis. Our results indicate that although the ribosome-binding residues are not fully conserved in LACK, both LACK and TbRACK1 co-sedimented with monosomes and polysomes in LACK/LACK and LACK/TbRACK1 L. major, respectively. LACK/LACK and LACK/TbRACK1 strains differed in their sensitivity to translation inhibitors implying that minor sequence differences between the RACK1 proteins can alter their functional properties. While biochemically distinguishable, both LACK/LACK and LACK/TbRACK1 lines were more tolerant of elevated temperatures, resistant to translation inhibitors, and displayed robust pathogenesis in vivo, contrasting to LACK/- parasites

Observation of associated near-side and away-side long-range correlations in √sNN=5.02 TeV proton-lead collisions with the ATLAS detector

Two-particle correlations in relative azimuthal angle (Δϕ) and pseudorapidity (Δη) are measured in √sNN=5.02  TeV p+Pb collisions using the ATLAS detector at the LHC. The measurements are performed using approximately 1  μb-1 of data as a function of transverse momentum (pT) and the transverse energy (ΣETPb) summed over 3.1<η<4.9 in the direction of the Pb beam. The correlation function, constructed from charged particles, exhibits a long-range (2<|Δη|<5) “near-side” (Δϕ∼0) correlation that grows rapidly with increasing ΣETPb. A long-range “away-side” (Δϕ∼π) correlation, obtained by subtracting the expected contributions from recoiling dijets and other sources estimated using events with small ΣETPb, is found to match the near-side correlation in magnitude, shape (in Δη and Δϕ) and ΣETPb dependence. The resultant Δϕ correlation is approximately symmetric about π/2, and is consistent with a dominant cos⁡2Δϕ modulation for all ΣETPb ranges and particle pT

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

Measurements of fiducial and differential cross sections for Higgs boson production in the diphoton decay channel at s√=8 TeV with ATLAS

Measurements of fiducial and differential cross sections are presented for Higgs boson production in proton-proton collisions at a centre-of-mass energy of s√=8 TeV. The analysis is performed in the H → γγ decay channel using 20.3 fb−1 of data recorded by the ATLAS experiment at the CERN Large Hadron Collider. The signal is extracted using a fit to the diphoton invariant mass spectrum assuming that the width of the resonance is much smaller than the experimental resolution. The signal yields are corrected for the effects of detector inefficiency and resolution. The pp → H → γγ fiducial cross section is measured to be 43.2 ±9.4(stat.) − 2.9 + 3.2 (syst.) ±1.2(lumi)fb for a Higgs boson of mass 125.4GeV decaying to two isolated photons that have transverse momentum greater than 35% and 25% of the diphoton invariant mass and each with absolute pseudorapidity less than 2.37. Four additional fiducial cross sections and two cross-section limits are presented in phase space regions that test the theoretical modelling of different Higgs boson production mechanisms, or are sensitive to physics beyond the Standard Model. Differential cross sections are also presented, as a function of variables related to the diphoton kinematics and the jet activity produced in the Higgs boson events. The observed spectra are statistically limited but broadly in line with the theoretical expectations