Delayed antibiotics for respiratory infections

Background: Concerns exist regarding antibiotic prescribing for acute respiratory tract infections (ARTIs) owing to adverse reactions, cost and antibacterial resistance. One strategy to reduce antibiotic prescribing is to provide prescriptions but to advise delay in the hope symptoms will resolve first. This is an update of a Cochrane Review originally published in 2007 and updated in 2010. Objectives: To evaluate the use of delayed antibiotics compared to immediate or no antibiotics as a prescribing strategy for ARTIs. We evaluated clinical outcomes including duration and severity measures for pain, malaise, fever, cough and rhinorrhoea in sore throat, acute otitis media, bronchitis (cough) and the common cold. We also evaluated the outcomes of antibiotic use, patient satisfaction, antibiotic resistance and re-consultation rates and use of alternative therapies. Search methods: We searched CENTRAL (The Cochrane Library 2013, Issue 2), which includes the Acute Respiratory Infection Group's Specialised Register; Ovid MEDLINE (January 1966 to February Week 3 2013); Ovid MEDLINE In-Process & Other Non-Indexed Citations (28 February 2013); EMBASE (1990 to 2013 Week 08); Science Citation Index - Web of Science (2007 to May 2012) and EBSCO CINAHL (1982 to 28 February 2013). Selection criteria: Randomised controlled trials (RCTs) involving participants of all ages defined as having an ARTI, where delayed antibiotics were compared to antibiotics used immediately or no antibiotics. Data collection and analysis: Three review authors independently extracted and collected data. Important adverse effects, including adverse effects of antibiotics and complications of disease, were included as secondary outcomes. We assessed the risk of bias of all included trials. We contacted trial authors to obtain missing information where available. Main results: Ten studies, with a total of 3157 participants, were included in this review. Heterogeneity of the 10 included studies and their results generally precluded meta-analysis with patient satisfaction being an exception. There was no difference between delayed, immediate and no prescribed antibiotics for the clinical outcomes evaluated in cough and common cold. In patients with acute otitis media (AOM) and sore throat immediate antibiotics were more effective than delayed for fever, pain and malaise in some studies. There were only minor differences in adverse effects with no significant difference in complication rates. Delayed antibiotics resulted in a significant reduction in antibiotic use compared to immediate antibiotics. A strategy of no antibiotics resulted in least antibiotic use. Patient satisfaction favoured immediate antibiotics over delayed (odds ratio (OR) 0.52; 95% confidence interval (CI) 0.35 to 0.76). Delayed and no antibiotics had similar satisfaction rates with both strategies achieving over 80% satisfaction (OR 1.44; 95% CI 0.99 to 2.10). There was no difference in re-consultation rates for immediate and delayed groups. None of the included studies evaluated antibiotic resistance. Authors' conclusions: Most clinical outcomes show no difference between strategies. Delay slightly reduces patient satisfaction compared to immediate antibiotics (87% versus 92%) but not compared to none (87% versus 83%). In patients with respiratory infections where clinicians feel it is safe not to prescribe antibiotics immediately, no antibiotics with advice to return if symptoms do not resolve is likely to result in the least antibiotic use, while maintaining similar patient satisfaction and clinical outcomes to delayed antibiotics

Estimating Discrete Markov Models From Various Incomplete Data Schemes

The parameters of a discrete stationary Markov model are transition probabilities between states. Traditionally, data consist in sequences of observed states for a given number of individuals over the whole observation period. In such a case, the estimation of transition probabilities is straightforwardly made by counting one-step moves from a given state to another. In many real-life problems, however, the inference is much more difficult as state sequences are not fully observed, namely the state of each individual is known only for some given values of the time variable. A review of the problem is given, focusing on Monte Carlo Markov Chain (MCMC) algorithms to perform Bayesian inference and evaluate posterior distributions of the transition probabilities in this missing-data framework. Leaning on the dependence between the rows of the transition matrix, an adaptive MCMC mechanism accelerating the classical Metropolis-Hastings algorithm is then proposed and empirically studied.Comment: 26 pages - preprint accepted in 20th February 2012 for publication in Computational Statistics and Data Analysis (please cite the journal's paper

Simple models of the chemical field around swimming plankton

Background. Cervical cancer is the fourth most common cancer in women, and we recently reported human leukocyte antigen (HLA) alleles showing strong associations with cervical neoplasia risk and protection. HLA ligands are recognized by killer immunoglobulin-like receptors (KIRs) expressed on a range of immune cell subsets, governing their proinflammatory activity. We hypothesized that the inheritance of particular HLA-KIR combinations would increase cervical neoplasia risk. Methods. Here, we used HLA and KIR dosages imputed from single-nucleotide polymorphism genotype data from 2143 cervical neoplasia cases and 13 858 healthy controls of European decent. Results. The following 4 novel HLA alleles were identified in association with cervical neoplasia, owing to their linkage disequilibrium with known cervical neoplasia-associated HLA-DRB1 alleles: HLA-DRB3*9901 (odds ratio [OR], 1.24; P = 2.49 × 10−9), HLA-DRB5*0101 (OR, 1.29; P = 2.26 × 10−8), HLA-DRB5*9901 (OR, 0.77; P = 1.90 × 10−9), and HLA-DRB3*0301 (OR, 0.63; P = 4.06 × 10−5). We also found that homozygosity of HLA-C1 group alleles is a protective factor for human papillomavirus type 16 (HPV16)-related cervical neoplasia (C1/C1; OR, 0.79; P = .005). This protective association was restricted to carriers of either KIR2DL2 (OR, 0.67; P = .00045) or KIR2DS2 (OR, 0.69; P = .0006). Conclusions. Our findings suggest that HLA-C1 group alleles play a role in protecting against HPV16-related cervical neoplasia, mainly through a KIR-mediated mechanism

A survey of physicians knowledge regarding awareness of maternal alcohol use and the diagnosis of FAS.

BACKGROUND: Alcohol is the most widely used drug in the world that is a human teratogen whose use among women of childbearing age has been steadily increasing. It is also probable that Fetal Alcohol Syndrome is under diagnosed by physicians. The objectives of this study were twofold: 1) to evaluate the experience, knowledge and confidence of family physicians with respect to the diagnosis of FAS and 2) to evaluate physicians awareness of maternal drinking patterns. METHODS AND PARTICIPANTS: A multiple choice anonymous questionnaire was sent to a randomly selected group of family physicians in the Metropolitan Toronto area. RESULTS: There was a 73% (75/103) total response rate; Overall, 6/75 (8%) of family physicians reported that they had actually diagnosed a child with FAS. 17.9% had suspicions but did not make a diagnosis and 12.7% reported making a referral to confirm the diagnosis. Physician rated confidence in the ability to diagnosis FAS was low, with 49% feeling they had very little confidence. 75% reported counselling pregnant women and 60.8% reported counselling childbearing women in general on the use of alcohol. When asked what screening test they used to detect the use of alcohol, 75% described frequency/quantity. Not a single respondent identified using the current accepted screening method for alcohol use (TWEAK) which is recommended by The Centre for Addiction and Mental Health. CONCLUSIONS: Family physicians do not feel confident about diagnosing FAS. None of the physicians were aware of the current screening methods to accurately gage alcohol use in pregnant and childbearing wome

Voids in the Large-Scale Structure

Voids are the most prominent feature of the LSS of the universe. Still, they have been generally ignored in quantitative analysis of it, essentially due to the lack of an objective tool to identify and quantify the voids. To overcome this, we present the Void-Finder algorithm, a novel tool for objectively quantifying galaxy voids. The algorithm classifies galaxies as either wall- or field-galaxies. Then it identifies voids in the wall-galaxy distribution. Voids are defined as continuous volumes that do not contain any wall-galaxies. The voids must be thicker than an adjustable limit, which is refined in successive iterations. We test the algorithm using Voronoi tessellations. By appropriate scaling of the parameters we apply it to the SSRS2 survey and to the IRAS 1.2 Jy. Both surveys show similar properties: ~50% of the volume is filled by the voids, which have a scale of at least 40 Mpc, and a -0.9 under-density. Faint galaxies populate the voids more than bright ones. These results suggest that both optically and IRAS selected galaxies delineate the same LSS. Comparison with the recovered mass distribution further suggests that the observed voids in the galaxy distribution correspond well to under-dense regions in the mass distribution. This confirms the gravitational origin of the voids.Comment: Submitted to ApJ; 33 pages, aaspp4 LaTeX file, using epsfig and natbib, 1 table, 12 PS figures. Complete gzipped version is available at http://shemesh.fiz.huji.ac.il/hagai/; uuencoded file is available at http://shemesh.fiz.huji.ac.il/papers/ep3.uu or ftp://shemesh.fiz.huji.ac.i

A hierarchy of voids: Much ado about nothing

We present a model for the distribution of void sizes and its evolution in the context of hierarchical scenarios of gravitational structure formation. We find that at any cosmic epoch the voids have a size distribution which is well-peaked about a characteristic void size which evolves self-similarly in time. This is in distinct contrast to the distribution of virialized halo masses which does not have a small-scale cut-off. In our model, the fate of voids is ruled by two processes. The first process affects those voids which are embedded in larger underdense regions: the evolution is effectively one in which a larger void is made up by the mergers of smaller voids, and is analogous to how massive clusters form from the mergers of less massive progenitors. The second process is unique to voids, and occurs to voids which happen to be embedded within a larger scale overdensity: these voids get squeezed out of existence as the overdensity collapses around them. It is this second process which produces the cut-off at small scales. In the excursion set formulation of cluster abundance and evolution, solution of the cloud-in-cloud problem, i.e., counting as clusters only those objects which are not embedded in larger clusters, requires study of random walks crossing one barrier. We show that a similar formulation of void evolution requires study of a two-barrier problem: one barrier is required to account for voids-in-voids, and the other for voids-in-clouds. Thus, in our model, the void size distribution is a function of two parameters, one of which reflects the dynamics of void formation, and the other the formation of collapsed objects.Comment: 23 pages, 9 figures, submitted to MNRA

The DEEP2 Galaxy Redshift Survey: The Evolution of Void Statistics from z~1 to z~0

We present measurements of the void probability function (VPF) at z~1 using data from the DEEP2 Redshift Survey and its evolution to z~0 using data from the Sloan Digital Sky Survey (SDSS). We measure the VPF as a function of galaxy color and luminosity in both surveys and find that it mimics trends displayed in the two-point correlation function, $\xi$; namely that samples of brighter, red galaxies have larger voids (i.e. are more strongly clustered) than fainter, blue galaxies. We also clearly detect evolution in the VPF with cosmic time, with voids being larger in comoving units at z~0. We find that the reduced VPF matches the predictions of a `negative binomial' model for galaxies of all colors, luminosities, and redshifts studied. This model lacks a physical motivation, but produces a simple analytic prediction for sources of any number density and integrated two-point correlation function, \bar{\xi}. This implies that differences in the VPF across different galaxy populations are consistent with being due entirely to differences in the population number density and \bar{\xi}. The robust result that all galaxy populations follow the negative binomial model appears to be due to primarily to the clustering of dark matter halos. The reduced VPF is insensitive to changes in the parameters of the halo occupation distribution, in the sense that halo models with the same \bar{\xi} will produce the same VPF. For the wide range of galaxies studied, the VPF therefore does not appear to provide useful constraints on galaxy evolution models that cannot be gleaned from studies of \bar{\xi} alone. (abridged)Comment: 17 pages, 15 figures, ApJ accepte

Delayed antibiotics for respiratory infections (Review)

BACKGROUND: Modest benefits of antibiotics for acute upper respiratory tract infections have to be weighed against common adverse reactions, cost and antibacterial resistance. There has been interest in ways to reduce antibiotic prescribing. One strategy is to provide the prescription, but advise delay of more than 48 hours before use, in the hope symptoms resolve first. Advocates suggest this will preserve patient satisfaction. This review asks what effect delayed antibiotics have on clinical outcomes of respiratory infections, antibiotic use and patient satisfaction. OBJECTIVES: To evaluate the prescribing strategy of delayed antibiotics for acute respiratory tract infections compared to immediate or no antibiotics for clinical outcomes, antibiotic use and patient satisfaction. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 4, 2006); MEDLINE (January 1966 to January Week 2, 2007), EMBASE (1990 to Week 2, 2007) and Current Contents - ISI Web of Knowledge (1998 to January 2007). SELECTION CRITERIA: Randomised controlled trials (RCTs) involving patients of all ages defined as having an acute respiratory infection were included in which delayed antibiotics were compared to antibiotics used immediately or no antibiotics. Outcomes measured included clinical outcomes, antibiotic use and patient satisfaction. DATA COLLECTION AND ANALYSIS: Data were collected and analysed by three review authors. MAIN RESULTS: Nine trials were eligible on the basis of design and relevant outcomes. For most clinical outcomes there was no difference between delayed, immediate and no antibiotics. Antibiotics prescribed immediately were more effective than delayed for fever, pain and malaise in some studies of patients with acute otitis media and sore throat but for other studies there was no difference. There was no difference for the common cold and bronchitis. Delaying antibiotic prescriptions reduced antibiotic use, and in three studies, reduced patient satisfaction compared to immediate antibiotics. In the other two studies comparing delayed and immediate antibiotics measuring satisfaction, there was no difference. Two studies also included a 'no antibiotics' arm for bronchitis and sore throat: there was no difference in symptom resolution nor patient satisfaction from antibiotic delay. In one study, but not the other, antibiotic use was significantly decreased with no, rather than delayed, antibiotics. AUTHORS' CONCLUSIONS: For most clinical outcomes there is no difference between the strategies. Immediate antibiotics was the strategy most likely to provide the best clinical outcomes in patients with sore throat and otitis media. Delaying or avoiding antibiotics, rather than providing them immediately, reduces antibiotic use for acute respiratory infections. Delay also reduced patient satisfaction in three trials, compared to immediate antibiotics with no difference in two other trials. Delaying antibiotics seems to have little advantage over avoiding them altogether where it is safe to do so

Jahn-Teller polarons and their superconductivity in a molecular conductor

We present a theoretical study of a possibility of superconductivity in a three dimensional molecular conductor in which the interaction between electrons in doubly degenerate molecular orbitals and an {\em intra}molecular vibration mode is large enough to lead to the formation of $E\otimes \beta$ Jahn-Teller small polarons. We argue that the effective polaron-polaron interaction can be attractive for material parameters realizable in molecular conductors. This interaction is the source of superconductivity in our model. On analyzing superconducting instability in the weak and strong coupling regimes of this attractive interaction, we find that superconducting transition temperatures up to 100 K are achievable in molecular conductors within this mechanism. We also find, for two particles per molecular site, a novel Mott insulating state in which a polaron singlet occupies one of the doubly degenerate orbitals on each site. Relevance of this study in the search for new molecular superconductors is pointed out.Comment: Submitted to Phys. Rev.

Gravitational collapse in an expanding background and the role of substructure II: Excess power at small scales and its effect of collapse of structures at larger scales

We study the interplay of clumping at small scales with the collapse and relaxation of perturbations at larger scales using N-Body simulations. We quantify the effect of collapsed haloes on perturbations at larger scales using two point correlation function, moments of counts in cells and mass function. The purpose of the study is twofold and the primary aim is to quantify the role played by collapsed low mass haloes in the evolution of perturbations at large scales, this is in view of the strong effect seen when the large scale perturbation is highly symmetric. Another reason for this study is to ask whether features or a cutoff in the initial power spectrum can be detected using measures of clustering at scales that are already non-linear. The final aim is to understand the effect of ignoring perturbations at scales smaller than the resolution of N-Body simulations. We find that these effects are ignorable if the scale of non-linearity is larger than the average inter-particle separation in simulations. Features in in the initial power spectrum can be detected easily if the scale of these features is in the linear regime, detecting such features becomes difficult as the relevant scales become non-linear. We find no effect of features in initial power spectra at small scales on the evolved power spectra at large scales. We may conclude that in general, the effect on evolution of perturbations at large scales of clumping on small scales is very small and may be ignored in most situations.Comment: Accepted for publication in MNRA