A survey of antibiotic administration practices involving patients with sepsis in UK Critical Care Units

Background: Alternative administration methods are emerging as a key area of research to improve clinical efficacy of antibiotics and address concerns regarding multi-drug resistance. Extended intermittent infusions or continuous infusions of antibiotics exhibiting time-dependent kill characteristics may be favourable in critically ill septic patients, but more evidence is needed to determine best practice. Objective: To find out whether any common practice exists for intravenous antibiotic administration in critical care units (CCUs) across UK NHS Trusts, and identify factors influencing the adoption of extended or continuous infusions. Setting: UK hospitals. Method: UK critical care pharmacists were invited to participate in a survey on behalf of all 240 CCUs via a UK Clinical Pharmacy Association message board. The survey focused on administration practices for 22 antibacterial agents. Main outcome measure: Antibiotic administration method. Results: Responses were received covering 64 CCUs, a rate of 26.2%. Common, but not uniform administration methods were apparent for 17/22 antibiotics. Four antibiotics (piperacillin/tazobactam, doripenem, meropenem and vancomycin) were more likely to be administered as continuous or extended-intermittent infusions. Choice of administration method was especially influenced by altered pk/pd properties in sepsis or severe burns patients, or by the presence of organisms requiring high MICs. Conclusion: Unlicensed alternative practices of antibiotic administration are widespread but only weak evidence exists of any patient benefit, such as reduced length of CCU stay, and none showing improvement in mortality. Further research is needed to determine whether extended infusion methods offer clinically meaningful advantages over shorter licenced administration methods in CCU patients

The clinical features of the piriformis syndrome: a systematic review

Piriformis syndrome, sciatica caused by compression of the sciatic nerve by the piriformis muscle, has been described for over 70 years; yet, it remains controversial. The literature consists mainly of case series and narrative reviews. The objectives of the study were: first, to make the best use of existing evidence to estimate the frequencies of clinical features in patients reported to have PS; second, to identify future research questions. A systematic review was conducted of any study type that reported extractable data relevant to diagnosis. The search included all studies up to 1 March 2008 in four databases: AMED, CINAHL, Embase and Medline. Screening, data extraction and analysis were all performed independently by two reviewers. A total of 55 studies were included: 51 individual and 3 aggregated data studies, and 1 combined study. The most common features found were: buttock pain, external tenderness over the greater sciatic notch, aggravation of the pain through sitting and augmentation of the pain with manoeuvres that increase piriformis muscle tension. Future research could start with comparing the frequencies of these features in sciatica patients with and without disc herniation or spinal stenosis

Asymmetric reproductive isolation between terminal forms of the salamander ring species Ensatina eschscholtzii revealed by fine-scale genetic analysis of a hybrid zone

<p>Abstract</p> <p>Background</p> <p>Ring species, exemplified by salamanders of the <it>Ensatina eschscholtzii </it>complex, represent a special window into the speciation process because they allow the history of species formation to be traced back in time through the geographically differentiated forms connecting the two terminal forms of the ring. Of particular interest is the nature and extent of reproductive isolation between the geographically terminal forms, in this case <it>E. e. eschscholtzii </it>and <it>E. e. klauberi</it>. Previous studies have documented infrequent hybridization at the end of the ring. Here, we report the first fine-scale genetic analysis of a hybrid zone between the terminal forms in southern California using individual-based Bayesian analyses of multilocus genetic data to estimate levels and direction of hybridization and maximum-likelihood analysis of linkage disequilibrium and cline shape to make inferences about migration and selection in the hybrid zone.</p> <p>Results</p> <p>The center of the hybrid zone has a high proportion of hybrids, about half of which were classified as F1s. Clines are narrow with respect to dispersal, and there are significant deviations from Hardy-Weinberg equilibrium as well as nonrandom associations (linkage disequilibria) between alleles characteristic of each parental type. There is cytonuclear discordance, both in terms of introgression and the geographic position of mitochondrial versus nuclear clines. Genetic disequilibrium is concentrated on the <it>eschscholtzii </it>side of the zone. Nearly all hybrids possess <it>klauberi </it>mtDNA, indicating that most hybrids are formed from female <it>klauberi </it>mating with male <it>eschscholtzii </it>or male hybrids (but not vice versa).</p> <p>Conclusions</p> <p>Our results are consistent with a tension zone trapped at an ecotone, with gene combinations characteristic of <it>klauberi </it>showing up on the <it>eschscholtzii </it>side of the zone due to asymmetric hybridization. We suggest that the observed asymmetry is best explained by increased discriminatory power of <it>eschscholtzii </it>females, or asymmetric postzygotic isolation. The relatively high frequency of hybrids, particularly F1s, contrasts with other contacts between the terminal forms, and with other contacts between other divergent <it>Ensatina </it>lineages, highlighting the diverse outcomes of secondary contact within a single species complex.</p

A meta-analysis of long-term effects of conservation agriculture on maize grain yield under rain-fed conditions

Conservation agriculture involves reduced tillage, permanent soil cover and crop rotations to enhance soil fertility and to supply food from a dwindling land resource. Recently, conservation agriculture has been promoted in Southern Africa, mainly for maize-based farming systems. However, maize yields under rain-fed conditions are often variable. There is therefore a need to identify factors that influence crop yield under conservation agriculture and rain-fed conditions. Here, we studied maize grain yield data from experiments lasting 5 years and more under rain-fed conditions. We assessed the effect of long-term tillage and residue retention on maize grain yield under contrasting soil textures, nitrogen input and climate. Yield variability was measured by stability analysis. Our results show an increase in maize yield over time with conservation agriculture practices that include rotation and high input use in low rainfall areas. But we observed no difference in system stability under those conditions. We observed a strong relationship between maize grain yield and annual rainfall. Our meta-analysis gave the following findings: (1) 92% of the data show that mulch cover in high rainfall areas leads to lower yields due to waterlogging; (2) 85% of data show that soil texture is important in the temporal development of conservation agriculture effects, improved yields are likely on well-drained soils; (3) 73% of the data show that conservation agriculture practices require high inputs especially N for improved yield; (4) 63% of data show that increased yields are obtained with rotation but calculations often do not include the variations in rainfall within and between seasons; (5) 56% of the data show that reduced tillage with no mulch cover leads to lower yields in semi-arid areas; and (6) when adequate fertiliser is available, rainfall is the most important determinant of yield in southern Africa. It is clear from our results that conservation agriculture needs to be targeted and adapted to specific biophysical conditions for improved impact

First Neutrino Observations from the Sudbury Neutrino Observatory

The first neutrino observations from the Sudbury Neutrino Observatory are presented from preliminary analyses. Based on energy, direction and location, the data in the region of interest appear to be dominated by 8B solar neutrinos, detected by the charged current reaction on deuterium and elastic scattering from electrons, with very little background. Measurements of radioactive backgrounds indicate that the measurement of all active neutrino types via the neutral current reaction on deuterium will be possible with small systematic uncertainties. Quantitative results for the fluxes observed with these reactions will be provided when further calibrations have been completed.Comment: Latex, 7 pages, 10 figures, Invited paper at Neutrino 2000 Conference, Sudbury, Canada, June 16-21, 2000 to be published in the Proceeding

A systems serology approach to the investigation of infection-induced antibody responses and protection in trachoma.

BACKGROUND: Ocular infections with Chlamydia trachomatis serovars A-C cause the neglected tropical disease trachoma. As infection does not confer complete immunity, repeated infections are common, leading to long-term sequelae such as scarring and blindness. Here, we apply a systems serology approach to investigate whether systemic antibody features are associated with susceptibility to infection. METHODS: Sera from children in five trachoma endemic villages in the Gambia were assayed for 23 antibody features: IgG responses towards two C. trachomatis antigens and three serovars [elementary bodies and major outer membrane protein (MOMP), serovars A-C], IgG responses towards five MOMP peptides (serovars A-C), neutralization, and antibody-dependent phagocytosis. Participants were considered resistant if they subsequently developed infection only when over 70% of other children in the same compound were infected. RESULTS: The antibody features assayed were not associated with resistance to infection (false discovery rate < 0.05). Anti-MOMP SvA IgG and neutralization titer were higher in susceptible individuals (p < 0.05 before multiple testing adjustment). Classification using partial least squares performed only slightly better than chance in distinguishing between susceptible and resistant participants based on systemic antibody profile (specificity 71%, sensitivity 36%). CONCLUSIONS: Systemic infection-induced IgG and functional antibody responses do not appear to be protective against subsequent infection. Ocular responses, IgA, avidity, or cell-mediated responses may play a greater role in protective immunity than systemic IgG

Twenty-first century brain banking. Processing brains for research: the Columbia University methods

Carefully categorized postmortem human brains are crucial for research. The lack of generally accepted methods for processing human postmortem brains for research persists. Thus, brain banking is essential; however, it cannot be achieved at the cost of the teaching mission of the academic institution by routing brains away from residency programs, particularly when the autopsy rate is steadily decreasing. A consensus must be reached whereby a brain can be utilizable for diagnosis, research, and teaching. The best diagnostic categorization possible must be secured and the yield of samples for basic investigation maximized. This report focuses on integrated, novel methods currently applied at the New York Brain Bank, Columbia University, New York, which are designed to reach accurate neuropathological diagnosis, optimize the yield of samples, and process fresh-frozen samples suitable for a wide range of modern investigations. The brains donated for research are processed as soon as possible after death. The prosector must have a good command of the neuroanatomy, neuropathology, and the protocol. One half of each brain is immersed in formalin for performing the thorough neuropathologic evaluation, which is combined with the teaching task. The contralateral half is extensively dissected at the fresh state. The anatomical origin of each sample is recorded using the map of Brodmann for the cortical samples. The samples are frozen at −160°C, barcode labeled, and ready for immediate disbursement once categorized diagnostically. A rigorous organization of freezer space, coupled to an electronic tracking system with its attached software, fosters efficient access for retrieval within minutes of any specific frozen samples in storage. This report describes how this achievement is feasible with emphasis on the actual processing of brains donated for research