Clinical prediction rules combining signs, symptoms and epidemiological context to distinguish influenza from influenza-like illnesses in primary care: a cross sectional study

<p>Abstract</p> <p>Background</p> <p>During an influenza epidemic prompt diagnosis of influenza is important. This diagnosis however is still essentially based on the interpretation of symptoms and signs by general practitioners. No single symptom is specific enough to be useful in differentiating influenza from other respiratory infections. Our objective is to formulate prediction rules for the diagnosis of influenza with the best diagnostic performance, combining symptoms, signs and context among patients with influenza-like illness.</p> <p>Methods</p> <p>During five consecutive winter periods (2002-2007) 138 sentinel general practitioners sampled (naso- and oropharyngeal swabs) 4597 patients with an influenza-like illness (ILI) and registered their symptoms and signs, general characteristics and contextual information. The samples were analysed by a DirectigenFlu-A&B and RT-PCR tests. 4584 records were useful for further analysis.</p> <p>Starting from the most relevant variables in a Generalized Estimating Equations (GEE) model, we calculated the area under the Receiver Operating Characteristic curve (ROC AUC), sensitivity, specificity and likelihood ratios for positive (LR+) and negative test results (LR-) of single and combined signs, symptoms and context taking into account pre-test and post-test odds.</p> <p>Results</p> <p>In total 52.6% (2409/4584) of the samples were positive for influenza virus: 64% (2066/3212) during and 25% (343/1372) pre/post an influenza epidemic. During and pre/post an influenza epidemic the LR+ of 'previous flu-like contacts', 'coughing', 'expectoration on the first day of illness' and 'body temperature above 37.8°C' is 3.35 (95%CI 2.67-4.03) and 1.34 (95%CI 0.97-1.72), respectively. During and pre/post an influenza epidemic the LR- of 'coughing' and 'a body temperature above 37.8°C' is 0.34 (95%CI 0.27-0.41) and 0.07 (95%CI 0.05-0.08), respectively.</p> <p>Conclusions</p> <p>Ruling out influenza using clinical and contextual information is easier than ruling it in. Outside an influenza epidemic the absence of cough and fever (> 37,8°C) makes influenza 14 times less likely in ILI patients. During an epidemic the presence of 'previous flu-like contacts', cough, 'expectoration on the first day of illness' and fever (>37,8°C) increases the likelihood for influenza threefold. The additional diagnostic value of rapid point of care tests especially for confirming influenza still has to be established.</p

Exploring the Gene Pool of Silver Fir in Southern Germany on the Search for Climate-Smart Seed Sources

Central European populations of silver fir (Abies alba Mill.) grow under a relatively wide amplitude of environmental conditions. Assuming that forest tree stands are locally adapted, the use of forest reproductive material from sites with limited water availability is expected to increase drought tolerance in future forests. At the same time, genetic diversity is of utmost importance as the basis of adaptation to a changing environment. Currently, a selection of potential sources for climate-smart reproductive material of silver fir is under way in Southern Germany. It is based on a multidisciplinary approach elucidating the genetic variation, site conditions, as well as tree resilience based on a dendroecological approach. The analysis encompasses a large number of stands representing the whole range of the species’ ecological requirements. The population genetic analysis based on molecular markers (nuclear microsatellites) provided important information concerning the gene pool of the species in Southern Germany. On one hand, it revealed genetic differentiation and transition zones between western and eastern clusters. On the other hand, the results indicated gradients and regional variation of genetic diversity. These patterns can be explained by post glacial recolonization and the peripheral character of the species at the northern limit of its distribution. Together with the outcomes of the site condition and dendroecological approaches, the results of the genetic analysis will be used to inform future provenance recommendations

The effect of giving influenza vaccination to general practitioners: a controlled trial [NCT00221676]

BACKGROUND: No efficacy studies of influenza vaccination given to GPs have yet been published. Therefore, our purpose was to assess the effect of an inactivated influenza vaccine given to GPs on the rate of clinical respiratory tract infections (RTIs) and proven influenza cases (influenza positive nose and throat swabs and a 4-fold titre rise), while adjusting for important covariates. METHODS: In a controlled trial during two consecutive winter periods (2002–2003 and 2003–2004) we compared (77 and 100) vaccinated with (45 and 40) unvaccinated GPs working in Flanders, Belgium. Influenza antibodies were measured immediately prior to and 3–5 weeks after vaccination, as well as after the influenza epidemic. During the influenza epidemic, GPs had to record their contact with influenza cases and their own RTI symptoms every day. If they became ill, the GPs had to take nose and throat swabs during the first 4 days. We performed a multivariate regression analysis for covariates using Generalized Estimating Equations. RESULTS: One half of the GPs (vaccinated or not) developed an RTI during the 2 influenza epidemics. During the two influenza periods, 8.6% of the vaccinated and 14.7% of the unvaccinated GPs had positive swabs for influenza (RR: 0.59; 95%CI: 0.28 – 1.24). Multivariate analysis revealed that influenza vaccination prevented RTIs and swab-positive influenza only among young GPs (ORadj: 0.35; 95%CI: 0.13 – 0.96 and 0.1; 0.01 – 0.75 respectively for 30-year-old GPs). Independent of vaccination, a low basic antibody titre against influenza (ORadj 0.57; 95%CI: 0.37 – 0.89) and the presence of influenza cases in the family (ORadj 9.24; 95%CI: 2.91 – 29) were highly predictive of an episode of swab-positive influenza. CONCLUSION: Influenza vaccination was shown to protect against proven influenza among young GPs. GPs, vaccinated or not, who are very vulnerable to influenza are those who have a low basic immunity against influenza and, in particular, those who have family members who develop influenza

Art-175 is a highly efficient antibacterial against multidrug-resistant strains and persisters of Pseudomonas aeruginosa

Artilysins constitute a novel class of efficient enzyme-based antibacterials. Specifically, they covalently combine a bacteriophage-encoded endolysin, which degrades the peptidoglycan, with a targeting peptide that transports the endolysin through the outer membrane of Gram-negative bacteria. Art-085, as well as Art-175, its optimized homolog with increased thermostability, are each composed of the sheep myeloid 29-amino acid (SMAP-29) peptide fused to the KZ144 endolysin. In contrast to KZ144, Art-085 and Art-175 pass the outer membrane and kill Pseudomonas aeruginosa, including multidrug-resistant strains, in a rapid and efficient (similar to 5 log units) manner. Time-lapse microscopy confirms that Art-175 punctures the peptidoglycan layer within 1 min, inducing a bulging membrane and complete lysis. Art-175 is highly refractory to resistance development by naturally occurring mutations. In addition, the resistance mechanisms against 21 therapeutically used antibiotics do not show cross-resistance to Art-175. Since Art-175 does not require an active metabolism for its activity, it has a superior bactericidal effect against P. aeruginosa persisters (up to > 4 log units compared to that of the untreated controls). In summary, Art-175 is a novel antibacterial that is well suited for a broad range of applications in hygiene and veterinary and human medicine, with a unique potential to target persister-driven chronic infections

Antibiotics for coughing in general practice: a questionnaire study to quantify and condense the reasons for prescribing

BACKGROUND: Antibiotics are being overprescribed in ambulant care, especially for respiratory tract infections (RTIs). Gaining insight into the actual reasons for prescribing remains important for the design of effective strategies to optimise antibiotic prescribing. We aimed to determine items of importance for the antibiotic prescribing decision and to make them operational for an intervention trial. METHODS: A postal questionnaire based upon focus group findings was sent to 316 Flemish general practitioners (GPs). On a verbal rating scale the GPs scored to what extent they consider the questionnaire items in decision making in case of suspected RTI in a coughing patient and how strongly the items support or counter antibiotic treatment. Factor analysis was used to condense the data. The relative importance of the yielded operational factors was assessed using Wilcoxon Matched Pairs test. RESULTS: 59.5% completed the study. Response group characteristics (mean age: 42.8 years; 65.9% men) approximated that of all Flemish GPs. Participants considered all the items included in the questionnaire: always the operational factor 'lung auscultation', often 'whether or not there is something unusual happening' – both medical reasons – and to a lesser extent 'non-medical reasons' (P < 0.001). Non-medical as well as medical reasons support antibiotic treatment, but non-medical reasons to a lesser extent (P < 0.001). CONCLUSION: This study quantified, condensed and confirmed the findings of previous focus group research. Practice guidelines and interventions to optimise antibiotic prescribing have to take non-medical reasons into account

Fluoxetine in Progressive Multiple Sclerosis (FLUOX-PMS) : study protocol for a randomized controlled trial

Background: Currently available disease-modifying treatments acting by modifying the immune response are ineffective in progressive multiple sclerosis (MS), which is caused by a widespread axonal degeneration. Mechanisms suspected to be involved in this widespread axonal degeneration are reduced axonal energy metabolism, axonal glutamate toxicity, and reduced cerebral blood flow. Fluoxetine might theoretically reduce axonal degeneration in MS because it stimulates energy metabolism through enhancing glycogenolysis, stimulates the production of brain-derived neurotrophic factor, and dilates cerebral arterioles. The current document presents the protocol of a clinical trial to test the hypothesis that fluoxetine slows down the progressive phase of MS. Methods/Design: The FLUOX-PMS trial is a multi-center, randomized, controlled and double-blind clinical study. A total of 120 patients with the diagnosis of either secondary or primary progressive MS will be treated either by fluoxetine (40 mg daily) or placebo for a total period of 108 weeks. The primary endpoint is the time to confirmed disease progression defined as either at least a 20% increase in the timed 25-Foot Walk or at least a 20% increase in the 9-Hole Peg Test. Secondary endpoints include the Hauser ambulation index, cognitive changes, fatigue, magnetic resonance imaging of the brain, and in a small subgroup optical coherence tomography. Discussion: The FLUOX-PMS trial will gives us information as to whether fluoxetine has neuroprotective effects in patients with progressive MS

A New Family of Lysozyme Inhibitors Contributing to Lysozyme Tolerance in Gram-Negative Bacteria

Lysozymes are ancient and important components of the innate immune system of animals that hydrolyze peptidoglycan, the major bacterial cell wall polymer. Bacteria engaging in commensal or pathogenic interactions with an animal host have evolved various strategies to evade this bactericidal enzyme, one recently proposed strategy being the production of lysozyme inhibitors. We here report the discovery of a novel family of bacterial lysozyme inhibitors with widespread homologs in gram-negative bacteria. First, a lysozyme inhibitor was isolated by affinity chromatography from a periplasmic extract of Salmonella Enteritidis, identified by mass spectrometry and correspondingly designated as PliC (periplasmic lysozyme inhibitor of c-type lysozyme). A pliC knock-out mutant no longer produced lysozyme inhibitory activity and showed increased lysozyme sensitivity in the presence of the outer membrane permeabilizing protein lactoferrin. PliC lacks similarity with the previously described Escherichia coli lysozyme inhibitor Ivy, but is related to a group of proteins with a common conserved COG3895 domain, some of them predicted to be lipoproteins. No function has yet been assigned to these proteins, although they are widely spread among the Proteobacteria. We demonstrate that at least two representatives of this group, MliC (membrane bound lysozyme inhibitor of c-type lysozyme) of E. coli and Pseudomonas aeruginosa, also possess lysozyme inhibitory activity and confer increased lysozyme tolerance upon expression in E. coli. Interestingly, mliC of Salmonella Typhi was picked up earlier in a screen for genes induced during residence in macrophages, and knockout of mliC was shown to reduce macrophage survival of S. Typhi. Based on these observations, we suggest that the COG3895 domain is a common feature of a novel and widespread family of bacterial lysozyme inhibitors in gram-negative bacteria that may function as colonization or virulence factors in bacteria interacting with an animal host