Planning and monitoring of patients for electrical cardioversion for atrial fibrillation

This study evaluated the waiting list for elective electrical cardioversion (ECV) for persistent atrial fibrillation (AF), focusing on when and why procedures were postponed. We compared the effects of management of the waiting list conducted by physicians versus management by nurse practitioners (NPs) and we evaluated the safety of our anticoagulating policy by means of bleeding or thromboembolic complications during and after ECV. Not all patients selected for ECV receive their treatment at the first planned instance due to a variety of reasons. These reasons are still undocumented. We evaluated 250 consecutive patients with persistent AF admitted to our clinic for elective ECV. Within 5 to 6 weeks, 186 of 242 patients (77%) received ECV. The main reason for postponing an ECV was an inadequate international normalised ratio (INR); other reasons included spontaneous sinus rhythm and switch to rate control. A total of 23 of the 147 patients (16%) managed by the research physician were postponed due to an inadequate INR at admission versus 4 out of 98 patients (4%) managed by NPs (p = 0.005) An inadequate INR is the main reason for postponing an ECV. Management of ECV by NPs is safe and leads to less postponing on admission

Non-invasive airway health assessment: Synchrotron imaging reveals effects of rehydrating treatments on mucociliary transit in-vivo

To determine the efficacy of potential cystic fibrosis (CF) therapies we have developed a novel mucociliary transit (MCT) measurement that uses synchrotron phase contrast X-ray imaging (PCXI) to non-invasively measure the transit rate of individual micron-sized particles deposited into the airways of live mice. The aim of this study was to image changes in MCT produced by a rehydrating treatment based on hypertonic saline (HS), a current CF clinical treatment. Live mice received HS containing a long acting epithelial sodium channel blocker (P308); isotonic saline; or no treatment, using a nebuliser integrated within a small-animal ventilator circuit. Marker particle motion was tracked for 20 minutes using PCXI. There were statistically significant increases in MCT in the isotonic and HS-P308 groups. The ability to quantify in vivo changes in MCT may have utility in pre-clinical research studies designed to bring new genetic and pharmaceutical treatments for respiratory diseases into clinical trials.Martin Donnelley, Kaye S. Morgan, Karen K. W. Siu, Nigel R. Farrow, Charlene S. Stahr, Richard C. Boucher, Andreas Fouras & David W. Parson

Proteinortho: Detection of (Co-)orthologs in large-scale analysis

<p>Abstract</p> <p>Background</p> <p>Orthology analysis is an important part of data analysis in many areas of bioinformatics such as comparative genomics and molecular phylogenetics. The ever-increasing flood of sequence data, and hence the rapidly increasing number of genomes that can be compared simultaneously, calls for efficient software tools as brute-force approaches with quadratic memory requirements become infeasible in practise. The rapid pace at which new data become available, furthermore, makes it desirable to compute genome-wide orthology relations for a given dataset rather than relying on relations listed in databases.</p> <p>Results</p> <p>The program <monospace>Proteinortho</monospace> described here is a stand-alone tool that is geared towards large datasets and makes use of distributed computing techniques when run on multi-core hardware. It implements an extended version of the reciprocal best alignment heuristic. We apply <monospace>Proteinortho</monospace> to compute orthologous proteins in the complete set of all 717 eubacterial genomes available at NCBI at the beginning of 2009. We identified thirty proteins present in 99% of all bacterial proteomes.</p> <p>Conclusions</p> <p><monospace>Proteinortho</monospace> significantly reduces the required amount of memory for orthology analysis compared to existing tools, allowing such computations to be performed on off-the-shelf hardware.</p

Antiangiogenic Agents in Combination with Chemotherapy in Patients with Advanced Non-Small Cell Lung Cancer

Most patients with non-small cell lung cancer (NSCLC) present with advanced disease requiring systemic chemotherapy. Treatment with the antiangiogenic agent bevacizumab in combination with standard platinum-based doublet chemotherapy has been shown to improve outcomes in patients with advanced NSCLC. Several multitargeted antiangiogenic tyrosine kinase inhibitors (e.g., sorafenib, sunitinib, cediranib, vandetanib, BIBF 1120, pazopanib, and axitinib) are also being evaluated in combination with standard chemotherapy. Here we review current clinical data with combination therapy involving antiangiogenic agents and cytotoxic chemotherapy in patients with advanced NSCLC

Current concepts of the management of dental extractions for patients taking warfarin

The document attached has been archived with permission from the Australian Dental Association. An external link to the publisher’s copy is included.Background: Controversy has surrounded the correct management of patients therapeutically anticoagulated with warfarin who require dental extractions. The risk of bleeding must be weighed up against the risk of thromboembolism when deciding whether to interfere with a patient's warfarin regimen. An improved understanding of the importance of fibrinolytic mechanisms in the oral cavity has resulted in the development of various local measures to enable these patients to be treated on an outpatient basis. Methods: A review of the literature was undertaken. This was supplemented by the authors' clinical trials and extensive clinical experience with anticoagulated patients. Results: Various protocols for treating patients taking warfarin have been reviewed and summarized and an overview of the haemostatic and fibrinolytic systems is presented. A protocol for management of warfarinized patients requiring dental extractions in the outpatient setting is proposed. Conclusions: Patients therapeutically anticoagulated with warfarin can be treated on an ambulatory basis, without interruption of their warfarin regimen provided appropriate local measures are used.G Carter, AN Goss, JV Lloyd, R Tocchett

Modulatory effects of heparin and short-length oligosaccharides of heparin on the metastasis and growth of LMD MDA-MB 231 breast cancer cells in vivo

Expression of the chemokine receptor CXCR4 allows breast cancer cells to migrate towards specific metastatic target sites which constitutively express CXCL12. In this study, we determined whether this interaction could be disrupted using short-chain length heparin oligosaccharides. Radioligand competition binding assays were performed using a range of heparin oligosaccharides to compete with polymeric heparin or heparan sulphate binding to I125 CXCL12. Heparin dodecasaccharides were found to be the minimal chain length required to efficiently bind CXCL12 (71% inhibition; P<0.001). These oligosaccharides also significantly inhibited CXCL12-induced migration of CXCR4-expressing LMD MDA-MB 231 breast cancer cells. In addition, heparin dodecasaccharides were found to have less anticoagulant activity than either a smaller quantity of polymeric heparin or a similar amount of the low molecular weight heparin pharmaceutical product, Tinzaparin. When given subcutaneously in a SCID mouse model of human breast cancer, heparin dodecasaccharides had no effect on the number of lung metastases, but did however inhibit (P<0.05) tumour growth (lesion area) compared to control groups. In contrast, polymeric heparin significantly inhibited both the number (P<0.001) and area of metastases, suggesting a differing mechanism for the action of polymeric and heparin-derived oligosaccharides in the inhibition of tumour growth and metastases

FRAGMATIC: A randomised phase III clinical trial investigating the effect of fragmin® added to standard therapy in patients with lung cancer

Background Venous thromboembolism (VTE) occurs when blood clots in the leg, pelvic or other deep vein (deep vein thrombosis) with or without transport of the thrombus into the pulmonary arterial circulation (pulmonary embolus). VTE is common in patients with cancer and is increased by surgery, chemotherapy, radiotherapy and disease progression. Low molecular weight heparin (LMWH) is routinely used to treat VTE and some evidence suggests that LMWH may also have an anticancer effect, by reduction in the incidence of metastases. The FRAGMATIC trial will assess the effect of adding dalteparin (FRAGMIN), a type of LMWH, to standard treatment for patients with lung cancer. Methods/Design The study design is a randomised multicentre phase III trial comparing standard treatment and standard treatment plus daily LMWH for 24 weeks in patients with lung cancer. Patients eligible for this study must have histopathological or cytological diagnosis of primary bronchial carcinoma (small cell or non-small cell) within 6 weeks of randomisation, be 18 or older, and must be willing and able to self-administer 5000 IU dalteparin by daily subcutaneous injection or have it administered to themselves or by a carer for 24 weeks. A total of 2200 patients will be recruited from all over the UK over a 3 year period and followed up for a minimum of 1 year after randomisation. Patients will be randomised to one of the two treatment groups in a 1:1 ratio, standard treatment or standard treatment plus dalteparin. The primary outcome measure of the trial is overall survival. The secondary outcome measures include venous thrombotic event (VTE) free survival, serious adverse events (SAEs), metastasis-free survival, toxicity, quality of life (QoL), levels of breathlessness, anxiety and depression, cost effectiveness and cost utility. Trial registration Current Controlled Trials ISRCTN8081276

Innovations in total knee replacement: new trends in operative treatment and changes in peri-operative management

The human knee joint can sustain damage due to injury, or more usually osteoarthritis, to one, two or all three of the knee compartments: the medial femorotibial, the lateral femorotibial and the patellofemoral compartments. When pain associated with this damage is unmanageable using nonsurgical techniques, knee replacement surgery might be the most appropriate course of action. This procedure aims to restore a pain-free, fully functional and durable knee joint. Total knee replacement is a well-established treatment modality, and more recently, partial knee replacement—more commonly known as bi- or unicompartmental knee replacement—has seen resurgence in interest and popularity. Combined with the use of minimally invasive surgery (MIS) techniques, gender-specific prosthetics and computer-assisted navigation systems, orthopaedic surgeons are now able to offer patients knee replacement procedures that are associated with (1) minimal risks during and after surgery by avoiding fat embolism, reducing blood loss and minimising soft tissue disruption; (2) smaller incisions; (3) faster and less painful rehabilitation; (4) reduced hospital stay and faster return to normal activities of daily living; (5) an improved range of motion; (6) less requirement for analgesics; and (7) a durable, well-aligned, highly functional knee. With the ongoing advancements in surgical technique, medical technology and prosthesis design, knee replacement surgery is constantly evolving. This review provides a personal account of the recent innovations that have been made, with a particular emphasis on the potential use of MIS techniques combined with computer-assisted navigation systems to treat younger, more physically active patients with resurfacing partial/total implant knee arthroplasty

Audio-Visual Speech Timing Sensitivity Is Enhanced in Cluttered Conditions

Events encoded in separate sensory modalities, such as audition and vision, can seem to be synchronous across a relatively broad range of physical timing differences. This may suggest that the precision of audio-visual timing judgments is inherently poor. Here we show that this is not necessarily true. We contrast timing sensitivity for isolated streams of audio and visual speech, and for streams of audio and visual speech accompanied by additional, temporally offset, visual speech streams. We find that the precision with which synchronous streams of audio and visual speech are identified is enhanced by the presence of additional streams of asynchronous visual speech. Our data suggest that timing perception is shaped by selective grouping processes, which can result in enhanced precision in temporally cluttered environments. The imprecision suggested by previous studies might therefore be a consequence of examining isolated pairs of audio and visual events. We argue that when an isolated pair of cross-modal events is presented, they tend to group perceptually and to seem synchronous as a consequence. We have revealed greater precision by providing multiple visual signals, possibly allowing a single auditory speech stream to group selectively with the most synchronous visual candidate. The grouping processes we have identified might be important in daily life, such as when we attempt to follow a conversation in a crowded room

Origin of an Alternative Genetic Code in the Extremely Small and GC–Rich Genome of a Bacterial Symbiont

The genetic code relates nucleotide sequence to amino acid sequence and is shared across all organisms, with the rare exceptions of lineages in which one or a few codons have acquired novel assignments. Recoding of UGA from stop to tryptophan has evolved independently in certain reduced bacterial genomes, including those of the mycoplasmas and some mitochondria. Small genomes typically exhibit low guanine plus cytosine (GC) content, and this bias in base composition has been proposed to drive UGA Stop to Tryptophan (Stop→Trp) recoding. Using a combination of genome sequencing and high-throughput proteomics, we show that an α-Proteobacterial symbiont of cicadas has the unprecedented combination of an extremely small genome (144 kb), a GC–biased base composition (58.4%), and a coding reassignment of UGA Stop→Trp. Although it is not clear why this tiny genome lacks the low GC content typical of other small bacterial genomes, these observations support a role of genome reduction rather than base composition as a driver of codon reassignment