Comparative Analysis of Cervical Spine Management in a Subset of Severe Traumatic Brain Injury Cases Using Computer Simulation

BACKGROUND: No randomized control trial to date has studied the use of cervical spine management strategies in cases of severe traumatic brain injury (TBI) at risk for cervical spine instability solely due to damaged ligaments. A computer algorithm is used to decide between four cervical spine management strategies. A model assumption is that the emergency room evaluation shows no spinal deficit and a computerized tomogram of the cervical spine excludes the possibility of fracture of cervical vertebrae. The study's goal is to determine cervical spine management strategies that maximize brain injury functional survival while minimizing quadriplegia. METHODS/FINDINGS: The severity of TBI is categorized as unstable, high risk and stable based on intracranial hypertension, hypoxemia, hypotension, early ventilator associated pneumonia, admission Glasgow Coma Scale (GCS) and age. Complications resulting from cervical spine management are simulated using three decision trees. Each case starts with an amount of primary and secondary brain injury and ends as a functional survivor, severely brain injured, quadriplegic or dead. Cervical spine instability is studied with one-way and two-way sensitivity analyses providing rankings of cervical spine management strategies for probabilities of management complications based on QALYs. Early collar removal received more QALYs than the alternative strategies in most arrangements of these comparisons. A limitation of the model is the absence of testing against an independent data set. CONCLUSIONS: When clinical logic and components of cervical spine management are systematically altered, changes that improve health outcomes are identified. In the absence of controlled clinical studies, the results of this comparative computer assessment show that early collar removal is preferred over a wide range of realistic inputs for this subset of traumatic brain injury. Future research is needed on identifying factors in projecting awakening from coma and the role of delirium in these cases

Cellular Bases of Barbiturate and Phenytoin Anticonvulsant Drug Action

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65509/1/j.1528-1157.1982.tb06093.x.pd

Expression of HA of HPAI H5N1 Virus at US2 Gene Insertion Site of Turkey Herpesvirus Induced Better Protection than That at US10 Gene Insertion Site

Herpesvirus of turkey (HVT) is being widely used as a vector for development of recombinant vaccines and US2 and US10 genes are often chosen as insertion sites for targeted gene expression. However, the different effects of the two genes for generation of recombinant HVT vaccines were unknown. In order to compare the effects of inserted genes in the two sites on the efficacy of the recombinant vaccines, host-protective haemagglutinin (HA) gene of the highly pathogenic avian influenza virus (HPAIV) H5N1 was inserted into either US2 or US10 gene locus of the HVT. The resulting US2 (rHVT-US2-HA) or US10 (rHVT-US10-HA) recombinant HVT viruses were used to infect chicken embryo fibroblasts. Plaques and the growth kinetics of rHVT-US2-HA-infected chicken embryo fibroblasts were similar to those of parental HVT whereas rHVT-US10-HA infected chicken embryo fibroblasts had different growth kinetics and plaque formation. The viremia levels in rHVT-US10-HA virus-infected chickens were significantly lower than those of rHVT-US2-HA group on 28 days post infection. The vaccine efficacy of the two recombinant viruses against H5N1 HPAIV and virulent Marek's disease virus was also evaluated in 1-day-old vaccinated chickens. rHVT-US2-HA-vaccinated chickens were better protected with reduced mortality than rHVT-US10-HA-vaccinated animals following HPAIV challenge. Furthermore, the overall hemaglutination inhibition antibody titers of rHVT-US2-HA-vaccinated chickens were higher than those of rHVT-US10-HA-vaccinated chickens. Protection levels against Marek's disease virus challenge following vaccination with either rHVT-US2-HA or rHVT-US10-HA, however, were similar to those of the parental HVT virus. These results, for the first time, indicate that US2 gene provides a favorable foreign gene insertion site for generation of recombinant HVT vaccines

Conservative treatment of a comminuted cervical fracture in a racehorse

The 'classical' or 'Hangman' neck fracture involves the odontoid peg (process) of the second cervical vertebra (C2), and is described as an axial, dens or odontoid peg fracture in both the veterinary and human literature. Possible surgical treatment in both foals and adult horses requires a technique that allows decompression, anatomical alignment and stabilisation of the odontoid fracture. A limited number of surgical cases in foals have been reported in literature, but never in an adult horse. A mature Irish Thoroughbred racehorse was diagnosed with a type 2a odontoid peg fracture. Clinical signs included reluctance to move the head and neck, a left hind limb lameness and a neurological status of grade 2. The horse was treated conservatively and raced successfully five months after the diagnosed injury

The management of non-valvular atrial fibrillation (NVAF) in Australian general practice: bridging the evidence-practice gap. A national, representative postal survey

<p>Abstract</p> <p>Background</p> <p>General practitioners (GPs) are ideally placed to bridge the widely noted evidence-practice gap between current management of NVAF and the need to increase anticoagulant use to reduce the risk of fatal and disabling stroke in NVAF. We aimed to identify gaps in current care, and asked GPs to identify potentially useful strategies to overcome barriers to best practice.</p> <p>Methods</p> <p>We obtained contact details for a random sample of 1000 GPs from a national commercial data-base. Randomly selected GPs were mailed a questionnaire after an advance letter. Standardised reminders were administered to enhance response rates. As part of a larger survey assessing GP management of NVAF, we included questions to explore GPs' risk assessment, estimates of stroke risk and GPs' perceptions of the risks and benefits of anticoagulation with warfarin. In addition, we explored GPs' perceived barriers to the wider uptake of anticoagulation, quality control of anticoagulation and their assessment of strategies to assist in managing NVAF.</p> <p>Results</p> <p>596 out of 924 eligible GPs responded (64.4% response rate). The majority of GPs recognised that the benefits of warfarin outweighed the risks for three case scenarios in which warfarin is recommended according to Australian guidelines. In response to a hypothetical case scenario describing a patient with a supratherapeutic INR level of 5, 41.4% of the 596 GPs (n = 247) and 22.0% (n = 131) would be "highly likely" or "likely", respectively, to cease warfarin therapy and resume at a lower dose when INR levels are within therapeutic range. Only 27.9% (n = 166/596) would reassess the patient's INR levels within one day of recording the supratherapeutic INR. Patient contraindications to warfarin was reported to "usually" or "always" apply to the patients of 40.6% (n = 242/596) of GPs when considering whether or not to prescribe warfarin. Patient refusal to take warfarin "usually" or "always" applied to the patients of 22.3% (n = 133/596) of GPs. When asked to indicate the usefulness of strategies to assist in managing NVAF, the majority of GPs (89.1%, n = 531/596) reported that they would find patient educational resources outlining the benefits and risks of available treatments "quite useful" or "very useful". Just under two-thirds (65.2%; n = 389/596) reported that they would find point of care INR testing "quite" or "very" useful. An outreach specialist service and training to enable GPs to practice stroke medicine as a special interest were also considered to be "quite" or "very useful" by 61.9% (n = 369/596) GPs.</p> <p>Conclusion</p> <p>This survey identified gaps, based on GP self-report, in the current care of NVAF. GPs themselves have provided guidance on the selection of implementation strategies to bridge these gaps. These results may inform future initiatives designed to reduce the risk of fatal and disabling stroke in NVAF.</p

Splint: the efficacy of orthotic management in rest to prevent equinus in children with cerebral palsy, a randomised controlled trial

<p>Abstract</p> <p>Background</p> <p>Range of motion deficits of the lower extremity occur in about the half of the children with spastic cerebral palsy (CP). Over time, these impairments can cause joint deformities and deviations in the children's gait pattern, leading to limitations in moblity. Preventing a loss of range of motion is important in order to reduce secondary activity limitations and joint deformities. Sustained muscle stretch, imposed by orthotic management in rest, might be an effective method of preventing a decrease in range of motion. However, no controlled study has been performed.</p> <p>Methods</p> <p>A single blind randomised controlled trial will be performed in 66 children with spastic CP, divided over three groups with each 22 participants. Two groups will be treated for 1 year with orthoses to prevent a decrease in range of motion in the ankle (either with static or dynamic knee-ankle-foot-orthoses) and a third group will be included as a control group and will receive usual care (physical therapy, manual stretching). Measurements will be performed at baseline and at 3, 6, 9 and 12 months after treatment allocation. The primary outcome measure will be ankle dorsiflexion at full knee extension, measured with a custom designed hand held dynamometer. Secondary outcome measures will be i) ankle and knee flexion during gait and ii) gross motor function. Furthermore, to gain more insight in the working mechanism of the orthotic management in rest, morphological parameters like achilles tendon length, muscle belly length, muscle fascicle length, muscle physiological cross sectional area length and fascicle pennation angle will be measured in a subgroup of 18 participants using a 3D imaging technique.</p> <p>Discussion</p> <p>This randomised controlled trial will provide more insight into the efficacy of orthotic management in rest and the working mechanisms behind this treatment. The results of this study could lead to improved treatments.</p> <p>Trial Registration Number</p> <p>Nederlands Trial Register <a href="http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=2091">NTR2091</a></p

Postcopulatory Sexual Selection Is Associated with Reduced Variation in Sperm Morphology

The evolutionary role of postcopulatory sexual selection in shaping male reproductive traits, including sperm morphology, is well documented in several taxa. However, previous studies have focused almost exclusively on the influence of sperm competition on variation among species. In this study we tested the hypothesis that intraspecific variation in sperm morphology is driven by the level of postcopulatory sexual selection in passerine birds.Using two proxy measures of sperm competition level, (i) relative testes size and (ii) extrapair paternity level, we found strong evidence that intermale variation in sperm morphology is negatively associated with the degree of postcopulatory sexual selection, independently of phylogeny.Our results show that the role of postcopulatory sexual selection in the evolution of sperm morphology extends to an intraspecific level, reducing the variation towards what might be a species-specific 'optimum' sperm phenotype. This finding suggests that while postcopulatory selection is generally directional (e.g., favouring longer sperm) across avian species, it also acts as a stabilising evolutionary force within species under intense selection, resulting in reduced variation in sperm morphology traits. We discuss some potential evolutionary mechanisms for this pattern

Individualized Cost-Effectiveness Analysis

John Ioannidis and Alan Garber discuss how to use incremental cost-effectiveness ratios (ICER) and related metrics so they can be useful for decision-making at the individual level, whether used by clinicians or individual patients

Topographical analysis of the subependymal zone neurogenic niche

The emerging model for the adult subependymal zone (SEZ) cell population indicates that neuronal diversity is not generated from a uniform pool of stem cells but rather from diverse and spatially confined stem cell populations. Hence, when analysing SEZ proliferation, the topography along the anterior-posterior and dorsal-ventral axes must be taken into account. However, to date, no studies have assessed SEZ proliferation according to topographical specificities and, additionally, SEZ studies in animal models of neurological/psychiatric disorders often fail to clearly specify the SEZ coordinates. This may render difficult the comparison between studies and yield contradictory results. More so, by focusing in a single spatial dimension of the SEZ, relevant findings might pass unnoticed. In this study we characterized the neural stem cell/progenitor population and its proliferation rates throughout the rat SEZ anterior-posterior and dorsal-ventral axes. We found that SEZ proliferation decreases along the anterior-posterior axis and that proliferative rates vary considerably according to the position in the dorsal-ventral axis. These were associated with relevant gradients in the neuroblasts and in the neural stem cell populations throughout the dorsal-ventral axis. In addition, we observed spatially dependent differences in BrdU/Ki67 ratios that suggest a high variability in the proliferation rate and cell cycle length throughout the SEZ; in accordance, estimation of the cell cycle length of the neuroblasts revealed shorter cell cycles at the dorsolateral SEZ. These findings highlight the need to establish standardized procedures of SEZ analysis. Herein we propose an anatomical division of the SEZ that should be considered in future studies addressing proliferation in this neural stem cell niche.Fundação para a Ciência e a Tecnologia (FCT