bluuebunny/crossref_metadata_2025 huggingface dataset:
A new method for tracking organ motion on diagnostic ultrasound images
Authors: Kubota Yoshiki , Matsumura Akihiko , Fukahori Mai , Minohara Shin‐ichi , Yasuda Shigeo , Nagahashi Hiroshi
Published: August 2014

Purpose:

Respiratory‐gated irradiation is effective in reducing the margins of a target in the case of abdominal organs, such as the liver, that change their position as a result of respiratory motion. However, existing technologies are incapable of directly measuring organ motion in real‐time during radiation beam delivery. Hence, the authors proposed a novel quantitative organ motion tracking method involving the use of diagnostic ultrasound images; it is noninvasive and does not entail radiation exposure. In the present study, the authors have prospectively evaluated this proposed method.

Methods:

The method involved real‐time processing of clinical ultrasound imaging data rather than organ monitoring; it comprised a three‐dimensional ultrasound device, a respiratory sensing system, and two PCs for data storage and analysis. The study was designed to evaluate the effectiveness of the proposed method by tracking the gallbladder in one subject and a liver vein in another subject. To track a moving target organ, the method involved the control of a region of interest (ROI) that delineated the target. A tracking algorithm was used to control the ROI, and a large number of feature points and an error correction algorithm were used to achieve long‐term tracking of the target. Tracking accuracy was assessed in terms of how well the ROI matched the center of the target.

Results:

The effectiveness of using a large number of feature points and the error correction algorithm in the proposed method was verified by comparing it with two simple tracking methods. The ROI could capture the center of the target for about 5 min in a cross‐sectional image with changing position. Indeed, using the proposed method, it was possible to accurately track a target with a center deviation of 1.54 ± 0.9 mm. The computing time for one frame image using our proposed method was 8 ms. It is expected that it would be possible to track any soft‐tissue organ or tumor with large deformations and changing cross‐sectional position using this method.

Conclusions:

The proposed method achieved real‐time processing and continuous tracking of the target organ for about 5 min. It is expected that our method will enable more accurate radiation treatment than is the case using indirect observational methods, such as the respiratory sensor method, because of direct visualization of the tumor. Results show that this tracking system facilitates safe treatment in clinical practice.
Evidence for interstellar origin of seven dust particles collected by the Stardust spacecraft
Authors: Westphal Andrew J. , Stroud Rhonda M. , Bechtel Hans A. , Brenker Frank E. , Butterworth Anna L. , Flynn George J. , Frank David R. , Gainsforth Zack , Hillier Jon K. , Postberg Frank , Simionovici Alexandre S. , Sterken Veerle J. , Nittler Larry R. , Allen Carlton , Anderson David , Ansari Asna , Bajt Saša , Bastien Ron K. , Bassim Nabil , Bridges John , Brownlee Donald E. , Burchell Mark , Burghammer Manfred , Changela Hitesh , Cloetens Peter , Davis Andrew M. , Doll Ryan , Floss Christine , Grün Eberhard , Heck Philipp R. , Hoppe Peter , Hudson Bruce , Huth Joachim , Kearsley Anton , King Ashley J. , Lai Barry , Leitner Jan , Lemelle Laurence , Leonard Ariel , Leroux Hugues , Lettieri Robert , Marchant William , Ogliore Ryan , Ong Wei Jia , Price Mark C. , Sandford Scott A. , Tresseras Juan-Angel Sans , Schmitz Sylvia , Schoonjans Tom , Schreiber Kate , Silversmit Geert , Solé Vicente A. , Srama Ralf , Stadermann Frank , Stephan Thomas , Stodolna Julien , Sutton Stephen , Trieloff Mario , Tsou Peter , Tyliszczak Tolek , Vekemans Bart , Vincze Laszlo , Von Korff Joshua , Wordsworth Naomi , Zevin Daniel , Zolensky Michael E. ,   30714 Stardust@home dusters
Published: August 2014

Can you spot a speck of space dust?

NASA's Stardust spacecraft has been collecting cosmic dust: Aerogel tiles and aluminum foil sat for nearly 200 days in the interstellar dust stream before returning to Earth. Citizen scientists identified most of the 71 tracks where particles were caught in the aerogel, and scanning electron microscopy revealed 25 craterlike features where particles punched through the foil. By performing trajectory and composition analysis, Westphal
et al.
report that seven of the particles may have an interstellar origin. These dust particles have surprisingly diverse mineral content and structure as compared with models of interstellar dust based on previous astronomical observations.

Science
, this issue p.
786
Genomic-scale exchange of mRNA between a parasitic plant and its hosts
Authors: Kim Gunjune , LeBlanc Megan L. , Wafula Eric K. , dePamphilis Claude W. , Westwood James H.
Published: August 2014

Strangleweed shares too much information

Because RNA normally functions within an individual cell, we generally think that we keep our RNAs to ourselves. Kim
et al.
now show that the parasitic dodder plant breaks that rule. When dodder attacks a host plant, it opens up a conduit through which messenger and perhaps other regulatory RNAs are exchanged between parasite and host. Because a single dodder plant can attack multiple hosts, such exchanges may underlie instances of genes transferring between species.

Science
, this issue p.
808
A boom in boomless seismology
Authors: Hand Eric
Published: August 2014

Densely packed sensors eavesdrop on Earth's hum.
Predictive Value of Testing Nasopharyngeal Samples for Respiratory Viruses in the Setting of Lower Respiratory Tract Disease
Authors: Hakki Morgan , Strasfeld Lynne M. , Townes John M.
Published: August 2014

To determine the predictive value of nasopharyngeal (NP) sample testing for respiratory viruses (RVs) in suspected lower respiratory tract disease, 72 paired NP and bronchoalveolar lavage (BAL) fluid specimen sets, mostly from transplant recipients or patients with hematologic malignancies, were analyzed. Overall, 31.3% of the specimens tested positive for an RV. In 19 sets (26.4%), the NP and BAL fluid specimens were both positive for an RV; in 3 sets (4.2%), the NP specimens were positive but the BAL fluid specimens were negative; and in 3 other sets, the NP specimens were negative but the BAL fluid specimens were positive. The positive and negative predictive values of the NP specimens were 86.4% and 94%, respectively.
Poor Performance of the Determine HIV-1/2 Ag/Ab Combo Fourth-Generation Rapid Test for Detection of Acute Infections in a National Household Survey in Swaziland
Authors: Duong Yen T. , Mavengere Yvonne , Patel Hetal , Moore Carole , Manjengwa Julius , Sibandze Dumile , Rasberry Christopher , Mlambo Charmaine , Li Zhi , Emel Lynda , Bock Naomi , Moore Jan , Nkambule Rejoice , Justman Jessica , Reed Jason , Bicego George , Ellenberger Dennis L. , Nkengasong John N. , Parekh Bharat S.
Published: August 2014

Fourth-generation HIV rapid tests (RTs) claim to detect both p24 antigen (Ag) and HIV antibodies (Ab) for early identification of acute infections, important for targeting prevention and reducing HIV transmission. In a nationally representative household survey in Swaziland, 18,172 adults, age 18 to 49 years, received home-based HIV rapid testing in 2010 and 2011. Of the 18,172 individuals, 5,822 (32.0%) were Ab positive (Ab+) by the Determine HIV-1/2 Ab/Ab combo test, and 5,789 (99.4%) of those were confirmed to be reactive in the Uni-Gold test. Determine combo identified 12 individuals as having acute infections (Ag+/Ab negative [Ab−]); however, none had detectable HIV-1 RNA and 8 of 12 remained HIV negative at their 6-week follow-up visit (4 were lost to follow-up). All RT-nonreactive samples were pooled and tested by nucleic acid amplification testing (NAAT) to identify acute infections. NAAT identified 13 (0.1%) of the 12,338 HIV antibody-negative specimens as HIV RNA positive, with RNA levels ranging from 300 to >10,000,000 copies/ml. However, none of them were Ag+by Determine combo. Follow-up testing of 12 of the 13 NAAT-positive individuals at 6 months demonstrated 12 seroconversions (1 individual was lost to follow-up). Therefore, the Determine combo test had a sensitivity of 0% (95% confidence interval, 0 to 28) and positive predictive value of 0% for the detection of acute infections. The ability of the 4th-generation Determine combo to detect antigen was very poor in Swaziland. Thus, the Determine combo test does not add any value to the current testing algorithm; rather, it adds additional costs and complexity to HIV diagnosis. The detection of acute HIV infections may need to rely on other testing strategies.
The Matrix Gene Segment Destabilizes the Acid and Thermal Stability of the Hemagglutinin of Pandemic Live Attenuated Influenza Virus Vaccines
Authors: O'Donnell Christopher D. , Vogel Leatrice , Matsuoka Yumiko , Jin Hong , Subbarao Kanta
Published: August 2014

The threat of future influenza pandemics and their potential for rapid spread, morbidity, and mortality has led to the development of pandemic vaccines. We generated seven reassortant pandemic live attenuated influenza vaccines (pLAIVs) with the hemagglutinin (HA) and neuraminidase (NA) genes derived from animal influenza viruses on the backbone of the six internal protein gene segments of the temperature sensitive, cold-adapted (
ca
) A/Ann Arbor/60 (H2N2) virus (AA/60
ca
) of the licensed seasonal LAIV. The pLAIV viruses were moderately to highly restricted in replication in seronegative adults; we sought to determine the biological basis for this restriction. Avian influenza viruses generally replicate at higher temperatures than human influenza viruses and, although they shared the same backbone, the pLAIV viruses had a lower shutoff temperature than seasonal LAIV viruses, suggesting that the HA and NA influence the degree of temperature sensitivity. The pH of HA activation of highly pathogenic avian influenza viruses was greater than human and low-pathogenicity avian influenza viruses, as reported by others. However, pLAIV viruses had a consistently higher pH of HA activation and reduced HA thermostability compared to the corresponding wild-type parental viruses. From studies with single-gene reassortant viruses bearing one gene segment from the AA/60
ca
virus in recombinant H5N1 or pH1N1 viruses, we found that the lower HA thermal stability and increased pH of HA activation were associated with the AA/60 M gene. Together, the impaired HA acid and thermal stability and temperature sensitivity likely contributed to the restricted replication of the pLAIV viruses we observed in seronegative adults.

IMPORTANCE
There is increasing evidence that the HA stability of influenza viruses depends on the virus strain and host species and that HA stability can influence replication, virulence, and transmission of influenza A viruses in different species. We investigated the HA stability of pandemic live attenuated influenza vaccine (pLAIV) viruses and observed that the pLAIV viruses consistently had a less stable HA than the corresponding wild-type influenza viruses. The reduced HA stability and temperature sensitivity of the pLAIV viruses may account for their restricted replication in clinical trials.
Combined Alphavirus Replicon Particle Vaccine Induces Durable and Cross-Protective Immune Responses against Equine Encephalitis Viruses
Authors: Reed Douglas S. , Glass Pamela J. , Bakken Russell R. , Barth James F. , Lind Cathleen M. , da Silva Luis , Hart Mary Kate , Rayner Jonathan , Alterson Kim , Custer Max , Dudek Jeanne , Owens Gary , Kamrud Kurt I. , Parker Michael D. , Smith Jonathan
Published: August 2014

Alphavirus replicons were evaluated as potential vaccine candidates for Venezuelan equine encephalitis virus (VEEV), western equine encephalitis virus (WEEV), or eastern equine encephalitis virus (EEEV) when given individually or in combination (V/W/E) to mice or cynomolgus macaques. Individual replicon vaccines or the combination V/W/E replicon vaccine elicited strong neutralizing antibodies in mice to their respective alphavirus. Protection from either subcutaneous or aerosol challenge with VEEV, WEEV, or EEEV was demonstrated out to 12 months after vaccination in mice. Individual replicon vaccines or the combination V/W/E replicon vaccine elicited strong neutralizing antibodies in macaques and demonstrated good protection against aerosol challenge with an epizootic VEEV-IAB virus, Trinidad donkey. Similarly, the EEEV replicon and V/W/E combination vaccine elicited neutralizing antibodies against EEEV and protected against aerosol exposure to a North American variety of EEEV. Both the WEEV replicon and combination V/W/E vaccination, however, elicited poor neutralizing antibodies to WEEV in macaques, and the protection conferred was not as strong. These results demonstrate that a combination V/W/E vaccine is possible for protection against aerosol challenge and that cross-interference between the vaccines is minimal.

IMPORTANCE
Three related viruses belonging to the genus
Alphavirus
cause severe encephalitis in humans: Venezuelan equine encephalitis virus (VEEV), western equine encephalitis virus (WEEV), and eastern equine encephalitis virus (EEEV). Normally transmitted by mosquitoes, these viruses can cause disease when inhaled, so there is concern that these viruses could be used as biological weapons. Prior reports have suggested that vaccines for these three viruses might interfere with one another. We have developed a combined vaccine for Venezuelan equine encephalitis, western equine encephalitis, and eastern equine encephalitis expressing the surface proteins of all three viruses. In this report we demonstrate in both mice and macaques that this combined vaccine is safe, generates a strong immune response, and protects against aerosol challenge with the viruses that cause Venezuelan equine encephalitis, western equine encephalitis, and eastern equine encephalitis.
Computational Prediction of Vaccine Strains for Human Influenza A (H3N2) Viruses
Authors: Steinbrück L. , Klingen T. R. , McHardy A. C.
Published: August 2014

Human influenza A viruses are rapidly evolving pathogens that cause substantial morbidity and mortality in seasonal epidemics around the globe. To ensure continued protection, the strains used for the production of the seasonal influenza vaccine have to be regularly updated, which involves data collection and analysis by numerous experts worldwide. Computer-guided analysis is becoming increasingly important in this problem due to the vast amounts of generated data. We here describe a computational method for selecting a suitable strain for production of the human influenza A virus vaccine. It interprets available antigenic and genomic sequence data based on measures of antigenic novelty and rate of propagation of the viral strains throughout the population. For viral isolates sampled between 2002 and 2007, we used this method to predict the antigenic evolution of the H3N2 viruses in retrospective testing scenarios. When seasons were scored as true or false predictions, our method returned six true positives, three false negatives, eight true negatives, and one false positive, or 78% accuracy overall. In comparison to the recommendations by the WHO, we identified the correct antigenic variant once at the same time and twice one season ahead. Even though it cannot be ruled out that practical reasons such as lack of a sufficiently well-growing candidate strain may in some cases have prevented recommendation of the best-matching strain by the WHO, our computational decision procedure allows quantitative interpretation of the growing amounts of data and may help to match the vaccine better to predominating strains in seasonal influenza epidemics.

IMPORTANCE
Human influenza A viruses continuously change antigenically to circumvent the immune protection evoked by vaccination or previously circulating viral strains. To maintain vaccine protection and thereby reduce the mortality and morbidity caused by infections, regular updates of the vaccine strains are required. We have developed a data-driven framework for vaccine strain prediction which facilitates the computational analysis of genetic and antigenic data and does not rely on explicit evolutionary models. Our computational decision procedure generated good matches of the vaccine strain to the circulating predominant strain for most seasons and could be used to support the expert-guided prediction made by the WHO; it thus may allow an increase in vaccine efficacy.
The VP4 Peptide of Hepatitis A Virus Ruptures Membranes through Formation of Discrete Pores
Authors: Shukla Ashutosh , Padhi Aditya K. , Gomes James , Banerjee Manidipa
Published: August 2014

Membrane-active peptides, components of capsid structural proteins, assist viruses in overcoming the host membrane barrier in the initial stages of infection. Several such peptides have been identified, and their roles in membrane fusion or disruption have been characterized through biophysical studies. In several members of the
Picornaviridae
family, the role of the VP4 structural peptide in cellular-membrane penetration is well established. However, there is not much information on the membrane-penetrating capsid components of hepatitis A virus (HAV), an unusual member of this family. The VP4 peptide of HAV differs from its analogues in other picornaviruses in being significantly shorter in length and in lacking a signal for myristoylation, thought to be a critical requisite for VP4-mediated membrane penetration. Here we report, for the first time, that the atypical VP4 in HAV contains significant membrane-penetrating activity. Using a combination of biophysical assays and molecular dynamics simulation studies, we show that VP4 integrates into membrane vesicles through its N-terminal region to finally form discrete pores of 5- to 9-nm diameter, which induces leakage in the vesicles without altering their overall size or shape. We further demonstrate that the membrane activity of VP4 is specific toward vesicles mimicking the lipid content of late endosomes at acidic pH. Taken together, our data indicate that VP4 might be essential for the penetration of host endosomal membranes and release of the viral genome during HAV entry.

IMPORTANCE
Hepatitis A virus causes acute hepatitis in humans through the fecal-oral route and is particularly prevalent in underdeveloped regions with poor hygienic conditions. Although a vaccine for HAV exists, its high cost makes it unsuitable for universal application in developing countries. Studies on host-virus interaction for HAV have been hampered due to a lack of starting material, since the virus is extremely slow growing in culture. Among the unknown aspects of the HAV life cycle is its manner of host membrane penetration, which is one of the most important initial steps in viral infection. Here, we present data to suggest that a small peptide, VP4, a component of the HAV structural polyprotein, might be essential in helping the viral genome cross cell membranes during entry. It is hoped that this work might help in elucidating the manner of initial host cell interaction by HAV.
Inhibition of Interleukin-2 Gene Expression by Human Herpesvirus 6B U54 Tegument Protein
Authors: Iampietro Mathieu , Morissette Guillaume , Gravel Annie , Flamand Louis
Published: August 2014

Human herpesvirus 6B (HHV-6B) is a ubiquitous pathogen causing lifelong infections in approximately 95% of humans worldwide. To persist within its host, HHV-6B has developed several immune evasion mechanisms, such as latency, during which minimal proteins are expressed, and the ability to disturb innate and adaptive immune responses. The primary cellular targets of HHV-6B are CD4+T cells. Previous studies by Flamand et al. (L. Flamand, J. Gosselin, I. Stefanescu, D. Ablashi, and J. Menezes, Blood 85:1263–1271, 1995) reported on the capacity of HHV-6A as well as UV-irradiated HHV-6A to inhibit interleukin-2 (IL-2) synthesis in CD4+lymphocytes, suggesting that viral structural components could be responsible for this effect. In the present study, we identified the HHV-6B U54 tegument protein (U54) as being capable of inhibiting IL-2 expression. U54 binds the calcineurin (CaN) phosphatase enzyme, causing improper dephosphorylation and nuclear translocation of NFAT (nuclear factor of activated T cells) proteins, resulting in suboptimalIL-2gene transcription. The U54 GISIT motif (amino acids 293 to 297), analogous to the NFAT PXIXIT motif, contributed to the inhibition of NFAT activation.

IMPORTANCEHuman herpesvirus 6A (HHV-6A) and HHV-6B are associated with an increasing number of pathologies. These viruses have developed strategies to avoid the immune response allowing them to persist in the host. Several studies have illustrated mechanisms by which HHV-6A and HHV-6B are able to disrupt host defenses (reviewed in L. Dagna, J. C. Pritchett, and P. Lusso, Future Virol. 8:273–287, 2013, doi:10.2217/fvl.13.7). Previous work informed us that HHV-6A is able to suppress synthesis of interleukin-2 (IL-2), a key immune growth factor essential for adequate T lymphocyte proliferation and expansion. We obtained evidence that HHV-6B also inhibits IL-2 gene expression and identified the mechanisms by which it does so. Our work led us to the identification of U54, a virion-associated tegument protein, as being responsible for suppression of IL-2. Consequently, we have identified HHV-6B U54 protein as playing a role in immune evasion. These results further contribute to our understanding of HHV-6 interactions with its human host and the efforts deployed to ensure its long-term persistence.
Inhibition of Breast Cancer Cell Proliferation through Disturbance of the Calcineurin/NFAT Pathway by Human Herpesvirus 6B U54 Tegument Protein
Authors: Iampietro Mathieu , Gravel Annie , Flamand Louis
Published: August 2014

Nuclear factor of activated T cell (NFAT) proteins are key regulators involved in multiple physiological mechanisms, such as immune response and cell growth. The capacity of selective calcineurin/NFAT inhibitors to decrease NFAT-dependent cancer cell progression, particularly in breast cancer, has already been demonstrated. In this study, we report a role for the human herpesvirus 6B (HHV-6B) U54 tegument protein in inhibiting MCF-7 breast cancer cell proliferation by inhibiting NFAT activation.
The Temperature-Sensitive and Attenuation Phenotypes Conferred by Mutations in the Influenza Virus PB2, PB1, and NP Genes Are Influenced by the Species of Origin of the PB2 Gene in Reassortant Viruses Derived from Influenza A/California/07/2009 and A/WSN/33 Viruses
Authors: Broadbent Andrew J. , Santos Celia P. , Godbout Rachel A. , Subbarao Kanta
Published: August 2014

Live attenuated influenza vaccines in the United States are derived from a human virus that is temperature sensitive (
ts
), characterized by restricted (≥100-fold) replication at 39°C. The
ts
genetic signature (
ts
sig) has been mapped to 5 loci in 3 genes: PB1 (391E, 581G, and 661T), PB2 (265S), and NP (34G). However, when transferred into avian and swine influenza viruses, only partial
ts
and attenuation phenotypes occur. To investigate the reason for this, we introduced the
ts
sig into the human origin virus A/WSN/33 (WSN), the avian-origin virus A/Vietnam/1203/04 (VN04), and the swine origin triple-reassortant 2009 pandemic H1N1 virus A/California/07/2009 (CA07), which contains gene segments from human, avian, and swine viruses. The VN04

ts

sig
and CA07

ts

sig
viruses replicated efficiently in Madin-Darby canine kidney (MDCK) cells at 39°C, but the replication of WSN

ts

sig
was restricted ≥100-fold compared to that at 33°C. Reassortant CA07

ts

sig
viruses were generated with individual polymerase gene segments from WSN, and vice versa. Only
ts
sig viruses with a PB2 gene segment derived from WSN were restricted in replication ≥100-fold at 39°C. In ferrets, the CA07

ts

sig
virus replicated in the upper and lower respiratory tract, but the replication of a reassortant CA07

ts

sig
virus with a WSN PB2 gene was severely restricted in the lungs. Taken together, these data suggest that the origin of the PB2 gene segment influences the
ts
phenotype
in vitro
and attenuation
in vivo
. This could have implications for the design of novel live vaccines against animal origin influenza viruses.

IMPORTANCE
Live attenuated influenza vaccines (LAIVs) on temperature-sensitive (
ts
) backbones derived from animal origin influenza viruses are being sought for use in the poultry and swine industries and to protect people against animal origin influenza. However, inserting the
ts
genetic signature from a licensed LAIV backbone fails to fully attenuate these viruses. Our data indicate this is associated with the presence of a PB2 gene segment derived from an avian influenza virus. We show that a reassortant 2009 pandemic H1N1 virus with the
ts
signature from a licensed LAIV donor virus is
ts in vitro
and attenuated
in vivo
when the PB2 gene is derived from a human origin virus but not from an avian virus. Our study provides information that could benefit the rational design of alternative LAIV backbones against animal origin influenza viruses.
Ultrasound-Guided Percutaneous Needle Electrolysis in Chronic Lateral Epicondylitis: Short-Term and Long-Term Results
Authors: Valera-Garrido Fermín , Minaya-Muñoz Francisco , Medina-Mirapeix Francesc
Published: August 2014

Background

Ultrasound (US)-guided percutaneous needle electrolysis (PNE) is a novel minimally invasive approach which consists of the application of a galvanic current through an acupuncture needle.

Objective

To evaluate the clinical and ultrasonographic effectiveness of a multimodal programme (PNE, eccentric exercise (EccEx) and stretching) in the short term for patients with chronic lateral epicondylitis, and to determine whether the clinical outcomes achieved decline over time.

Methods

A one-way repeated measures study was performed in a clinical setting in 36 patients presenting with lateral epicondylitis. The patients received one session of US-guided PNE per week over 4–6 weeks, associated with a home programme of EccEx and stretching. The main outcome measures were severity of pain, disability (Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire), structural tendon changes (US), hypervascularity and patients’ perceptions of overall outcome. Measurements at 6, 26 and 52 weeks follow-up included recurrence rates (increase in severity of pain or disability compared with discharge), perception of overall outcome and success rates.

Results

All outcome measures registered significant improvements between pre-intervention and discharge. Most patients (n=30, 83.3%) rated the overall outcome as ‘successful’ at 6 weeks. The ultrasonographic findings showed that the hypoechoic regions and hypervascularity of the extensor carpi radialis brevis changed significantly. At 26 and 52 weeks, all participants (n=32) perceived a ‘successful’ outcome. Recurrence rates were null after discharge and at follow-up at 6, 26 and 52 weeks.

Conclusions

Symptoms and degenerative structural changes of chronic lateral epicondylitis are reduced after US-guided PNE associated with EccEx and stretching, with encouragingly low recurrences in the mid to long term.

Trial Registration Number

ClinicalTrials.gov identifier: NCT02085928.
A rapidly growing lid lump
Authors: Koay Su-Yin , Lee Richard M H , Hugkulstone Charles , Rodrigues Ian Aureliano Stephen
Published: August 2014

A 97-year-old woman presented with a 5-month history of a rapidly growing, painless, left upper eyelid lesion. Examination revealed a large vascularised, ulcerated nodule on the left upper lid, causing significant ptosis. Wide local excision of the lesion was performed and the wound was left to heal by secondary intention. Histology and immunohistochemistry of the lesion confirmed a diagnosis of Merkel cell carcinoma, a rare primary malignancy of the eyelid which has significant morbidity and mortality. Although uncommon, this diagnosis should always be considered in any patient with a rapidly growing lid lump. In view of the patient's age, known dementia and family wishes, the patient was managed conservatively, with no further investigations performed. She was due to be followed up in clinic on a regular basis, but has since died from other causes.
The effects of sodium-glucose co-transporter 2 inhibitors in patients with type 2 diabetes: protocol for a systematic review with meta-analysis of randomised trials
Authors: Storgaard Heidi , Gluud Lise Lotte , Christensen Mikkel , Knop Filip Krag , Vilsbøll Tina
Published: August 2014

Introduction

Sodium-glucose co-transporter 2 inhibitors (SGLT-2i) increase urinary glucose excretion through a reduced renal glucose reabsorption. We plan to perform a systematic review of SGLT-2i for treatment of type 2 diabetes.

Methods and analysis

A systematic review with meta-analyses of randomised clinical trials on SGLT-2i versus placebo, other oral glucose lowering drugs or insulin for patients with type 2 diabetes will be performed. The primary end point will be the glycated haemoglobin. Secondary end points will include changes in body weight, body mass index, fasting plasma glucose, plasma cholesterol, kidney and liver blood tests, blood pressure and adverse events. Electronic (the Cochrane Library, MEDLINE, EMBASE and the Science Citation Index) and manual searches will be performed. Meta-analyses will be performed and the results presented as mean differences for continuous outcomes and risk differences for dichotomous outcomes, both with 95% CIs. Subgroup, sensitivity, regression and sequential analyses will be performed to evaluate intertrial heterogeneity, bias and the robustness of results due to cumulative testing.

Ethics and dissemination

The study will contribute to the knowledge regarding the beneficial and harmful effects of SGLT-2i in patients with type 2 diabetes. We plan to publish the study irrespective of the results.

Results

The study will be disseminated by peer-review publication and conference presentation.

Trial registration number

PROSPERO CRD42014008960
Reduced risk of recurrent myocardial infarction in homozygous carriers of the chromosome 9p21 rs1333049 C risk allele in the contemporary percutaneous coronary intervention era: a prospective observational study
Authors: Hara Masahiko , Sakata Yasuhiko , Nakatani Daisaku , Suna Shinichiro , Usami Masaya , Matsumoto Sen , Ozaki Kouichi , Nishino Masami , Sato Hiroshi , Kitamura Tetsuhisa , Nanto Shinsuke , Hamasaki Toshimitsu , Tanaka Toshihiro , Hori Masatsugu , Komuro Issei
Published: August 2014

Objectives

Chromosome 9p21 single nucleotide polymorphism (SNP) is a susceptibility variant for acute myocardial infarction (AMI) in the primary prevention setting. However, it is controversial whether this SNP is also associated with recurrent myocardial infarction (ReMI) in the secondary prevention setting. The purpose of this study is to evaluate the impact of chromosome 9p21 SNP on ReMI in patients receiving secondary prevention programmes after AMI.

Design

A prospective observational study.

Setting

Osaka Acute Coronary Insufficiency Study (OACIS) in Japan.

Participants

2022 patients from the OACIS database.

Interventions

Genotyping of the 9p21 rs1333049 variant.

Primary outcome measures

ReMI event after survival discharge for 1 year.

Results

A total of 43 ReMI occurred during the 1 year follow-up period. Although the rs1333049 C allele had an increased susceptibility to their first AMI in an additive model when compared with 1373 healthy controls (OR 1.20, 95% CI 1.09 to 1.33, p=2.3*10−4), patients with the CC genotype had a lower incidence of ReMI at 1 year after discharge of AMI (log-rank p=0.005). The adjusted HR of the CC genotype as compared with the CG/GG genotypes was 0.20 (0.06 to 0.65, p=0.007). Subgroup analysis demonstrated that the association between the rs1333049 CC genotype and a lower incidence of 1 year ReMI was common to all subgroups.

Conclusions

Homozygous carriers of the rs1333049 C allele on chromosome 9p21 showed a reduced risk of 1 year ReMI in the contemporary percutaneous coronary intervention era, although the C allele had conferred susceptibility to their first AMI.
THE SHOCKING TRUTH—TIME BETWEEN DEFIBRILLATION ATTEMPTS DURING PRE-HOSPITAL RESUSCITATION OF VF CARDIAC ARREST
Authors: Mitchell Kirsty , Short Steven , Clegg Gareth
Published: August 2014

Objectives & Background

Timely defibrillation and high-quality cardiopulmonary resuscitation (CPR) are the only pre-hospital interventions which have been demonstrated to save lives after OHCA (out-of-hospital cardiac arrest). Standard resuscitation using the advanced life support (ALS) algorithm specifies a period of two minutes of CPR after delivering a shock before re-assessing the rhythm and delivering a further shock if indicated. Recent work has focused on improving quality of CPR, but few studies have examined how effectively defibrillation is carried out in pre-hospital practice. This study aims to assess the timing of shocks during resuscitation after OHCA.

Methods

Defibrillator (Philips MRX) data is routinely downloaded after all OHCA in Edinburgh as part of routine audit. We analysed a consecutive series of arrests 1-April-2013 and 31-March-2014. Only arrests where >1 consecutive shocks were delivered were included, in order to allow inter-shock intervals to be calculated. Event Review Pro software (Philips) was used to visualise ECG and CPR data, to determine time between shocks with no interrupting period of non-shockable rhythm. Inter-shock intervals between 2:00 min and 2:30 min were deemed compliant with ALS guidelines.

Results

There were 189 cardiac arrests in the study period, with 70 cases eligible for inclusion. Mean time between shocks was 3:06 min (0:15 min–18:23 min, SD 1:54 min). 53% of inter-shock intervals were >2:30 min and 21% were <2:00 min. Only 26% of intervals were compliant with ALS guidelines. Figure 1 shows a scatter plot of the inter-shock intervals for each OHCA resuscitation episode. The red bar indicates the 'compliant' zone of 2:00–2:30 min.

Conclusion

The majority of intervals between shocks delivered in out-of-hospital cardiac arrest were non-compliant with current ALS guidelines. Whilst the underlying reasons for this finding remain unclear, the extreme outliers appeared to be related to transporting the patient from the scene of the arrest. It was still the case, however, that the majority of defibrillation attempts were delivered either earlier than 2 min or later than 2:30 min, which may reflect a loss of situational awareness in the distracting environment of an OHCA resuscitation. Further work needs to be done to establish the cause of this deviation from recommended shock timing in order to develop strategies to optimise practice.
WHAT IS THE ROLE OF ADVANCED NURSE PRACTITIONERS (ANPs) IN A MAJOR TRAUMA TEAM (MTT)?
Authors: Adkins Charlotte V , Trivedy Chetan , Stanhope Benjamin
Published: August 2014

Objectives & Background

ANPs are autonomous practitioners and form a core part of many Emergency Departments (EDs). However, there is little data on their role in major trauma and deployment within MTTs. The project aimed to explore clinicians' views on the role of ANPs within MTTs in Major Trauma Centres (MTCs).

Methods

A two-part project using an anonymised questionnaire was designed to explore attitudes towards the role of ANPs as part of the MTT. Part one was distributed to members of the MTT at an MTC in the West Midlands (the author's workplace); using an online survey tool, part two was sent to the clinical leads of all 26 MTCs in England. Resultant data includes current national use of ANPs in MTTs, reasons for inclusion/exclusion, and understanding, attitudes and opinions regarding their involvement.

Results

At the author's workplace, 93% of responses felt that ANPs should form part of an MTT (remaining 7% unsure). Data suggests that there is a lack of understanding of the ANP role (45% stating they fully understand the role, 55% partially) and of ANP training in regard to managing major trauma, with resultant uncertainty regarding abilities. 76% feel ANPs should have a role in clinical assessment of patients, 68% that they should have a role in breathing interventions (ie manual ventilation) and 90% circulatory interventions (cannulation/pelvic splint application). 85% of national MTCs responded; 81% of these have ANPs in their ED but only 11% utilise ANPs as a core MTT member. Where ANPs are part of the MTT, their roles tend to be in line with normal nursing roles (ie circulatory interventions 100%, drug preparation/administration 50%). Only 50% of respondents utilised ANPs for clinical assessment, part of their day-to-day role. 13% felt that ANPs do not have a role in MTTs. Barriers to ANP involvement include rota capacity (35%), clinical competence (25%), training priorities (22%), supervision (16%), ANP training (52%), ability (68%) and skills (36%).

Conclusion

The project data shows that, although ANPs are now part of many ED teams and are increasingly taking on extended autonomous ED roles, there is still a level of uncertainty and lack of clarity on their role as part of an MTT. There needs to be a national policy outlining and standardising ANP training, qualification and utilisation within the ED as well as a robust programme to promote their education, training and skills, to optimise their deployment.
ADHERENCE TO THE NICE HEAD INJURY GUIDELINES 2007 AND 2014 IN ANTICOAGULATED PATIENTS
Authors: Kuczawski Maxine , Mason Suzanne , Stevenson Matt , Holmes Michael , Teare Marion D , Ramlakhan Shammi , Goodacre Steve , Morris Francis , Harper Rosemary
Published: August 2014

Objectives & Background

Until January 2014, The National Institute of Clinical Excellence (NICE) Head Injury Guidelines (CG56) issued to clinicians advised anticoagulated patients with a head injury should only receive CT imaging if loss of consciousness or amnesia was experienced. These guidelines have recently been updated to advise CT imaging for all anticoagulated patients. We aimed to investigate how closely the 2007 guidelines were followed and whether the guideline update will mean considerable changes to existing practice.

Methods

Data was analysed from the AHEAD Study, a large prospective observational multicentre study involving 33 emergency departments in England and Scotland. Within the cohort of anticoagulated patients, those that complied with the NICE guidelines (2007 and 2014) were identified and categorised into 3 groups depending on the NICE CT imaging advice a) <1 hr, b) <8 hrs and c) all patients. The symptoms, treatment and outcomes of these patients were described and compared with actual clinical practice.

Results

Applying NICE 2007 criteria to the 3534 patients, 779 (22%) patients were identified as eligible candidates for CT imaging—within 1hr, 558 (72%) patients and within 8hrs, 221 (28%) patients. Of the eligible patients, 82% (n=641) actually did have a CT head scan of which 17% (n=111) had a significant head injury-related finding. Adherence in the time to CT was achieved for 16% within 1hr and 90% within 8hrs (Mean 285 and 243 minutes respectively). Neurosurgery was performed in 14 (1.8%) patients and 27 (3.5%) patients died of a head injury-related death. Of those patients that did not fulfil the NICE 2007 criteria (n=2755), 54% (n=1473) had CT imaging on average 431 minutes after ED attendance. A significant CT finding was found in 5.9% (n=87) patients, neurosurgery performed in 5 (0.2%) patients and 15 (0.5%) patients died of a head injury-related death. Applying the updated NICE 2014 advice which states all anticoagulated patients should receive CT imaging, found only 60% (n=2114) of this cohort received it.

Conclusion

The majority of patients that fulfilled the NICE 2007 criteria did have CT imaging performed (82%). However, a significant number of patients not fulfilling the criteria also had CT imagining performed. Overall, 60% of the anticoagulated patient cohort had CT imaging, this will need to increase considerably to follow the updated NICE 2014 guidelines of CT imaging for all patients.
DO GP USER-FEES AFFECT A&E USAGE? GP CHARGES DRIVE A&E DEMAND, FOR RICHER, FOR POORER
Authors: Arun-Castro Sriskantharajah
Published: August 2014

Objectives & Background

To establish whether the need to pay for GP services including consultations, phlebotomy and referrals, affects how households utilise A&E in Jersey. To describe the reasons why households have previously utilised A&E instead of a GP.

Background

Outside of the NHS, Jersey's primary healthcare service is funded through direct user-fees and co-payments, whilst secondary care including the island's sole Emergency Department is free. The average GP consultation in Jersey costs £37.50.

Methods

A postal questionnaire survey exploring household health seeking behaviours was commissioned, designed and piloted following a user-led approach with the Jersey Consumer Council's Primary Care Users Group. A census design was applied to collect data from all households (41,595) during the month of July 2012. Inclusion criteria: All households in Jersey, one return per household. Exclusion Criteria: Incomplete/soiled questionnaires. Data were managed in SPSS, with a population-based weighting applied to maximise the representativeness of the sample.

Results

Data were obtained from 6,508 households, reflecting a response rate of 16% (6508/41,595).

One in three respondents (1934/5998; 32.2%) stated that their household had previously chosen to attend A&E instead of a GP practice. Primary care user-fees were the most commonly cited reason explaining this behaviour, reported by 43.9% of respondents (849/1934).

Almost one in five households (1099/5950; 18.5%) stated that they had attended A&E for problems they self-reported as being “neither an accident nor emergency.” Both highest (>£104,000) and lowest (<£25,000) annual income groups contributed to this use of A&E. 17.5% (86/492) of high income households and 20.8% (412/1977) low income households reported using A&E for such non-urgent care.

Conclusion

This study confirms that in Jersey, GP user-fees create cost-related demand for the Emergency Department.

Willingness to pay for primary care does not reflect ability to pay in Jersey, evidenced by both high and low income groups reporting use of A&E for non-urgent problems.

Further research is indicated to examine whether A&E cost-related demand would arise if GP user-fees were introduced in the NHS.
CIRCULATING LEUCINE-RICHα-2-GLYCOPROTEIN glycoprotein 1 TO DETECT ACUTE APPENDICITIS IN PATIENTS WITH ACUTE ABDOMINAL PAIN
Authors: Rainer Timothy H , Leung Ling Yan , Chan Pui Yee Cangel , Leung Yuk Ki , Lai Bo San Paul , Cheung Yue Sun , Graham Colin A
Published: August 2014

Objectives & Background

Circulating leucine-rich α-2-glycoprotein-1 (LRG1) protein has been found in the plasma and urine of patients with acute appendicitis (AA) and may be useful for diagnosis. The present study aimed to investigate whether circulating LRGI mRNA levels also improve the early diagnosis of AA.

Methods

A prospective study was conducted between December 2011 and October 2012 on patients presenting to the ED with acute abdominal pain (<7 days of symptom onset). AA was confirmed if there were histopathological findings of an inflammed or necrotic appendix in appendicectomy specimens. Real-time polymerase chain reaction was used to analyze whole blood LRG1 mRNA level taken from these patients within 24 hours of arrival (mean 12.4 h). The primary outcome was AA.

Results

Eighty-four consecutive patients (40 (47.6%) with AA and 44 (52.4%) without AA; mean age 35 years; 41.6% males) were recruited. Median whole blood LRG1 mRNA levels were higher in AA patients than in non-AA patients (2.2 (95% CI 1.3–2.6) vs 1.3 (95% CI 0.8–1.8)×105copies/ml,p=0.0122). Of 40 AA patients, 13 (32.5%) were diagnosed as complicated AA, and had median LRG mRNA level higher than in patients with simple AA (3.2 (95% CI 2.2–4.1) vs 1.6 (95% CI 1.1–2.5)×105 copies/ml,p=0.0479). At a LRG1 mRNA cutoff of 1.9×105 copies/ml, the optimal sensitivity and specificity were 57.5% and 72.7% respectively. At this cutoff, the odds ratio for AA was 3.6 (95% CI 1.5–9.0;p=0.0047).

Conclusion

Whole blood LRG1 mRNA levels may be useful to diagnose simple and complicated AA from other causes of abdominal pain.

Acknowledgement

This research study was supported by a Direct Grant for Research from the Chinese University of Hong Kong (reference no.: 2041642) (HK$18000).
FIX FREDDIE! – PULLING STRINGS TO REDUCE PRESSURE ON MINORS
Authors: Cleugh Francesca , Langseth Annette , Clements Charlotte , Salam Menai , Manfredi Lucia
Published: August 2014

Objectives & Background

Emergency and urgent care workload is becoming unsustainable.1 2NW London has higher than average use of unscheduled care;3significant proportion with low acuity conditions.2 4 5As a paediatric emergency care provider, Imperial College Healthcare (ICHT) recognise a need to become proactive in tackling this challenge. ICHT collaborated with a professional puppet company to produce Fix Freddie!6A pilot tour ran in NW London March and April 2014. Objectives included:

better understanding of how local community accesses unscheduled care

gathering professionals across the whole system to support families in feeling confident to navigate system and care for their children's health needs

reducing pressures on unscheduled care system

Methods

Pilot tour explored different settings and workshop styles. Audience 484 children, 134 adults(image1)

Parents and carers asked to complete pre show questionnaire about child health and services. After the show issues raised explored in various ways:

small parent focus groups

classroom-based discussion

fete style event promoting conversations with professionals

Feedback obtained with Post-It comments on “Freddie Feedback” poster(image 2).

Filmed to capture impact of events on children, parents, professionals.

Leaflet distributed with information about how to seek advice, self management and local services.

Results:Pre show questionnaire

Completed by 46 parents of 85 children. 53% white british; 47% diverse ethnicies.

Chart A -How they seek child health advice(image 3)

Chart B -Services use when worried(image 3)

Parents consistently worried by fever: 52% would seek GP review 41% would go to ED.

Attended ED and the GP with similar illnesses.

26% reported issues in accessing care, primarily lack of same day GP appointments.

Key themes surfaced from Fix Freddie! Feedback(image 4)

Better understanding of local services, notably 111

Improved confidence managing minor ailments

Positive feedback for puppet show and events

Immediate impact captured on film, currently being analysed. Short documentary being produced by June 2014.

Conclusion

Fix Freddie! has provided a fun and engaging way to make connections across the whole system, facilitating co-design of local solutions to problems of healthcare accessibility and confidence in self management. Local CCG commissioners are keen to fund a wider local tour and we are looking at next steps to broaden the reach of events.