Emergency versus semi-elective management of mandible fractures: a Maxillofacial Trainee Research Collaborative (MTReC) study.

INTRODUCTION: Recent evidence suggests that acute emergency management of mandible fractures does not improve surgical outcomes yet is associated with increased financial burden. Current NHS policy advocating for increased adoption of day-case and semi-elective surgical procedures to reduce bed strain must be balanced with providing timely, effective treatment. Our research aims to determine patient groups currently managed via semi-elective admission and whether this can be extended to other groups to provide safe and effective management of mandible fractures. METHODS: A multi-national trainee-led audit of mandibular fractures across 49 units was completed by the Maxillofacial Trainee Research Collaborative (MTReC). Each unit prospectively collected data on fractures on admission and at follow-up. Data collected included patient demographics, behaviour, health, injury, timing to intervention and surgical complications. RESULTS: Data were collected on 947 mandibular fractures. Of the surgically managed patients, 649 (90%) were managed via acute emergency admission at the time of presentation, while 68 (10%) were managed semi-electively. Patient demographics, injury pattern and mechanism appeared to significantly affect timing of management, whereas patient behaviour, health status, timing of injury and presentation did not. Semi-elective management was associated with a significantly shorter inpatient duration (0.9 versus 1.9 days, p=0.000) with no differences in readmission, antibiotic usage or surgical complications (p=1.000, RR 1.030). CONCLUSION: Our study demonstrates the efficacy of planned admissions and semi-elective management of mandibular fractures. Simple mandibular fractures in compliant patients are suitable for semi-elective treatment. Holistic patient assessment and tailored surgical planning is crucial in determining admission modality to effectively manage mandibular trauma.

Inner ear drug delivery through a cochlear implant: Pharmacokinetics in a Macaque experimental model.

OBJECTIVES: The method of drug delivery directly into the cochlea with an implantable pump connected to a CI electrode array ensures long-term delivery and effective dose control, and also provides the possibility to use different drugs. The objective is to develop a model of inner ear pharmacokinetics of an implanted cochlea, with the delivery of FITC-Dextran, in the non-human primate model. DESIGN: A preclinical cochlear electrode array (CI Electrode Array HL14DD, manufactured by Cochlear Ltd.) attached to an implantable peristaltic pump filled with FITC-Dextran was implanted unilaterally in a total of 15 Macaca fascicularis (Mf). Three groups were created (5 Mf in each group), according to three different drug delivery times: 2 hours, 24 hours and 7 days. Perilymph (10 samples, 1µL each) was sampled from the apex of the cochlea and measured immediately after extraction with a spectrofluorometer. After scarifying the specimens, x-Rays and histological analysis were performed. RESULTS: Surgery, sampling and histological analysis were performed successfully in all specimens. FITC-Dextran quantification showed different patterns, depending on the delivery group. In the 2 hours injection experiment, an increase in FITC-Dextran concentrations over the sample collection time was seen, reaching maximum concentration peaks (420-964µM) between samples 5 and 7, decreasing in successive samples, without returning to baseline. The 24-hours and 7-days injection experiments showed even behaviour throughout the 10 samples obtained, reaching a plateau with mean concentrations ranging from 2144 to 2564 µM and from 1409 to 2502µM, respectively. Statistically significant differences between the 2 hours and 24 hours groups (p = 0.001) and between the 2 hours and 7 days groups (p = 0.037) were observed, while between the 24 hours and 7 days groups no statistical differences were found. CONCLUSIONS: This experimental study shows that a model of drug delivery and pharmacokinetics using an active pump connected to an electrode array is feasible in Mf. An infusion time ranging from 2 to 24 hours is required to reach a maximum concentration peak at the apex. It establishes then an even concentration profile from base to apex that is maintained throughout the infusion time in Mf. Flow mechanisms during injection and during sampling that may explain such findings may involve cochlear aqueduct flow as well as the possible existence of substance exchange from scala tympani to extracellular spaces, such as the modiolar space or the endolymphatic sinus, acting as a substance reservoir to maintain a relatively flat concentration profile from base to apex during sampling. Leveraging the learnings achieved by experimentation in rodent models, we can move to experiment in non-human primate with the aim of achieving a useful model that provides transferrable data to human pharmacokinetics. Thus, it may broaden clinical and therapeutic approaches to inner ear diseases.

Faunal mediated carbon export from mangroves in an arid area.

The outwelling paradigm argues that mangrove and saltmarsh wetlands export much excess production to downstream marine systems. However, outwelling is difficult to quantify and currently 40-50% of fixed carbon is unaccounted for. Some carbon is thought outwelled through mobile fauna, including fish, which visit and feed on mangrove produce during tidal inundation or early life stages before moving offshore, yet this pathway for carbon outwelling has never been quantified. We studied faunal carbon outwelling in three arid mangroves, where sharp isotopic gradients across the boundary between mangroves and down-stream systems permitted spatial differentiation of source of carbon in animal tissue. Stable isotope analysis (C, N, S) revealed 22-56% of the tissue of tidally migrating fauna was mangrove derived. Estimated consumption rates showed that 1.4% (38 kg C ha-1 yr-1) of annual mangrove litter production was directly consumed by migratory fauna, with <1% potentially exported. We predict that the amount of faunally-outwelled carbon is likely to be highly correlated with biomass of migratory fauna. While this may vary globally, the measured migratory fauna biomass in these arid mangroves was within the range of observations for mangroves across diverse biogeographic ranges and environmental settings. Hence, this study provides a generalized prediction of the relatively weak contribution of faunal migration to carbon outwelling from mangroves and the current proposition, that the unaccounted-for 40-50% of mangrove C is exported as dissolved inorganic carbon, remains plausible.

Validation of the Seegene RV15 multiplex PCR for the detection of influenza A subtypes and influenza B lineages during national influenza surveillance in hospitalized adults.

Background. The Serious Outcomes Surveillance Network of the Canadian Immunization Research Network (CIRN SOS) has been performing active influenza surveillance since 2009 (ClinicalTrials.gov identifier: NCT01517191). Influenza A and B viruses are identified and characterized using real-time reverse-transcriptase polymerase chain reaction (RT-PCR), and multiplex testing has been performed on a subset of patients to identify other respiratory virus aetiologies. Since both methods can identify influenza A and B, a direct comparison was performed.Methods. Validated real-time RT-PCRs from the World Health Organization (WHO) to identify influenza A and B viruses, characterize influenza A viruses into the H1N1 or H3N2 subtypes and describe influenza B viruses belonging to the Yamagata or Victoria lineages. In a subset of patients, the Seeplex RV15 One-Step ACE Detection assay (RV15) kit was also used for the detection of other respiratory viruses.Results. In total, 1111 nasopharyngeal swabs were tested by RV15 and real-time RT-PCRs for influenza A and B identification and characterization. For influenza A, RV15 showed 98.0 % sensitivity, 100 % specificity and 99.7 % accuracy. The performance characteristics of RV15 were similar for influenza A subtypes H1N1 and H3N2. For influenza B, RV15 had 99.2 % sensitivity, 100 % specificity and 99.8 % accuracy, with similar assay performance being shown for both the Yamagata and Victoria lineages.Conclusions. Overall, the detection of circulating subtypes of influenza A and lineages of influenza B by RV15 was similar to detection by real-time RT-PCR. Multiplex testing with RV15 allows for a more comprehensive respiratory virus surveillance in hospitalized adults, without significantly compromising the reliability of influenza A or B virus detection.

The Impact of Prior Season Vaccination on Subsequent Influenza Vaccine Effectiveness to Prevent Influenza-related Hospitalizations Over 4 Influenza Seasons in Canada.

BACKGROUND: Recent studies have demonstrated the possibility of negative associations between prior influenza vaccines and subsequent influenza vaccine effectiveness (VE), depending on season and strain. We investigated this association over 4 consecutive influenza seasons (2011-2012 through 2014-2015) in Canada. METHODS: Using a matched test-negative design, laboratory-confirmed influenza cases and matched test-negative controls admitted to hospitals were enrolled. Patients were stratified into 4 groups according to influenza vaccine history (not vaccinated current and prior season [referent], vaccinated prior season only, vaccinated current season only, and vaccinated both current and prior season). Conditional logistic regression was used to estimate VE; prior vaccine impact was assessed each season for overall effect and effect stratified by age (<65 years, ≥65 years) and type/subtype (A/H1N1, A/H3N2, influenza B). RESULTS: Overall, mainly nonsignificant associations were observed. Trends of nonsignificant decreased VE among patients repeatedly vaccinated in both prior and current season relative to the current season only were observed in the A/H3N2-dominant seasons of 2012-2013 and 2014-2015. Conversely, in 2011-2012, during which B viruses circulated, and in 2013-2014, when A/H1N1 circulated, being vaccinated in both seasons tended to result in a high VE in the current season against the dominant circulating subtype. CONCLUSIONS: Prior vaccine impact on subsequent VE among Canadian inpatients was mainly nonsignificant. Even in circumstances where we observed a trend of negative impact, being repeatedly vaccinated was still more effective than not receiving the current season's vaccine. These findings favor continuation of annual influenza vaccination recommendations, particularly in older adults. CLINICAL TRIALS REGISTRATION: NCT01517191.

Drain Usage in Head and Neck Surgery: A National Survey of Thirty-five Surgeons across Ten Units

Introduction Drain usage is commonplace in head and neck surgery. There is an increasing body of literature disputing their routine placement in certain procedures. The aim of this study is to explore modern-day practice in terms of drain usage and the use of haemostatic agents. Methods A simple questionnaire was devised and sent to 35 ENT Surgeons across 10 units nationally. Results There was an overall response rate of 77.1% (n=27). There was considerable heterogeneity amongst surgeons in terms of indication for insertion, how the decision is made to remove the drain and if any alternative/adjunctive haemostatic agents are being used. Discussion The management of drains is poorly defined and guidelines are lacking. With increased pressure on resources, the risk of infection and discomfort to the patient, further reflection is required to evaluate if careful patient selection rather than habitual drain insertion in every case is more appropriate.

Resistance patterns of Enterobacteriaceae in urines are similar in symptomatic and asymptomatic patients.

Antibiograms of urine cultures are being used to guide empiric treatment for urinary tract infections (UTIs). However, roughly 50% of urine cultures are from patients with asymptomatic bacteriuria (ABU). It is unclear whether Enterobacteriaceae in ABU patients have similar resistance patterns as UTI patients. Hence, we aimed to compare the antimicrobial resistance patterns in patients with ABU to patients with symptomatic UTI. We found no major differences in resistance patterns, and therefore empiric treatment choices can be guided by antibiograms that include ABU patients.

Polyps, grommets and eosinophilic granulomatosis with polyangiitis.

OBJECTIVE: To explore the link between nasal polyposis, refractory otitis media with effusion and eosinophilic granulomatosis with polyangiitis. METHODS: A retrospective observational study was carried out of patients diagnosed with refractory otitis media with effusion necessitating grommet insertion and who had nasal polyps. Patients were evaluated to determine if they fulfilled the diagnostic criteria of eosinophilic granulomatosis with polyangiitis. RESULTS: Sixteen patients (10 males and 6 females) were identified. The mean age of grommet insertion was 45.4 years. The mean number of grommets inserted per patient was 1.6. The mean number of nasal polypectomies was 1.7. All 16 patients had paranasal sinus abnormalities and otitis media with effusion, 14 had asthma, 9 had serological eosinophilia and 7 had extravascular eosinophilia. Nine patients met the diagnostic criteria for eosinophilic granulomatosis with polyangiitis. CONCLUSION: The co-presence of nasal polyps and resistant otitis media with effusion should raise the possibility of eosinophilic granulomatosis with polyangiitis.

Cardiac cephalgia: a diagnostic headache.

A 73-year-old man presented with a 6-month history of exertional headaches. Exercise tolerance test demonstrated progressive ischaemic changes concomitant with worsening headache. Cardiac cephalgia was diagnosed and his symptoms resolved after coronary artery bypass surgery. Cardiac cephalgia may occasionally present as exertional headache without chest symptoms.

Benthic surveys of the historic pearl oyster beds of Qatar reveal a dramatic ecological change.

The study aimed to confirm the presence of historic oyster banks of Qatar and code the biotopes present. The research also collated historical records and scientific publications to create a timeline of fishery activity. The oyster banks where once an extremely productive economic resource however, intense overfishing, extreme environmental conditions and anthropogenic impacts caused a fishery collapse. The timeline highlighted the vulnerability of ecosystem engineering bivalves if overexploited. The current status of the oyster banks meant only one site could be described as oyster dominant. This was unexpected as the sites were located in areas which once supported a highly productive oyster fishery. The research revealed the devastating effect that anthropogenic impacts can have on a relatively robust marine habitat like an oyster bed and it is hoped these findings will act as a driver to investigate and map other vulnerable habitats within the region before they too become compromised.

60 YEARS OF POMC: Lipotropin and beta-endorphin: a perspective.

Many important fields of research had a humble origin. In the distant past, A J P Martin's discovery that amino acids could be separated by paper chromatography and Moore and Stein's use of columns for quantitative amino acid analysis provided the first steps towards the determination of structure in complex biologically active molecules. They opened the door to reveal the essential relationship that exists between structure and function. In molecular endocrinology, for example, striking advances have been made by chemists with their expertise in the identification of structure working with biologists who contributed valuable knowledge and experience. Advantage was gained from the convergence of different background, and it is notable that the whole is greater than the sum. In the determination of structure, it may be recalled that four of the world's great pioneers (Archibald Martin, Rodney Porter, Fred Sanger and Vincent du Vigneaud) were acknowledged for their fundamental contributions when individually they were awarded the Nobel Prize. They foresaw that the identification of structure would prove of outstanding importance in the future. Indeed, study of the structures of ß-endorphin and enkephalin and the different forms of opiate activity they engender has led to a transformation in our understanding of chemical transmission in the brain.

Variation in Arterial Access for Invasive Coronary Procedures in New Zealand: A National Analysis (ANZACS-QI 5).

BACKGROUND: Radial arterial access (RA) and femoral arterial access (FA) rates for invasive coronary angiography (ICA) vary widely internationally. The European Society of Cardiology (ESC) suggests default RA is feasible. We aim to investigate the variation in RA rates across all New Zealand public hospitals. METHODS AND RESULTS: Patient characteristics, procedural details, and inpatient outcome data were collected in the All New Zealand Acute Coronary Syndrome - Quality Improvement (ANZACS-QI) registry on consecutive patients undergoing ICA over five months. Of the 5894 ICAs 81% were via RA. Hospitals averaged 25 - 176 procedures/month (46.5% - 96.4% via RA). Operators averaged 17 procedures/month. Those performing more than 20 ICAs/month had RA rates between 61% - 99%. Of the 75 operators, 69% met the ESC recommendation. After multivariable adjustment higher operator (RR 1.12, CI 1.09 - 1.30) and hospital (RR 1.21, CI 1.15 - 1.28) volume were independent predictors of RA. Those with prior CABG (RR 0.51, CI 0.45 - 0.57), STEMI <12h (RR 0.91, CI 0.87 - 0.96), and female sex (RR 0.96, CI 0.94 - 0.99) were less likely to receive RA. CONCLUSIONS: New Zealand has a high RA rate for ICAs. Rates vary substantially between both operators and centres. Radial arterial was highest amongst the highest volume operators and centres.

Whole-genome sequencing in hierarchy with pulsed-field gel electrophoresis: the utility of this approach to establish possible sources of MRSA cross-transmission.

BACKGROUND: In order to study the micro-epidemiology of meticillin-resistant Staphylococcus aureus (MRSA) effectively, the molecular typing method used must be able to distinguish between different MRSA strains. Pulsed-field gel electrophoresis (PFGE) can detect small genetic differences but is limited in its potential to distinguish isolates within a major lineage. Whole-genome sequencing (WGS) provides sufficient resolution to support or exclude links between otherwise indistinguishable isolates, but lacks the practical utility of conventional typing methods. AIM: To explore the utility of WGS in a hierarchical approach with PFGE to help establish possible sources of MRSA cross-transmission in the intensive care setting. METHODS: Possible transmission routes from donor to recipient via the hands of staff, the air or environmental surfaces were identified. Focused molecular typing used PFGE to explore these transmission hypotheses. WGS was applied when an acquisition event involved a common PFGE pulsotype. FINDINGS: Thirty-eight of the 78 acquisition events could not be explored as clinical isolates were not available. PFGE excluded all potential donors from 26 of the remaining 40 acquisition events, but did identify a probable source in 14 new colonizations. Within the hypotheses tested, PFGE supported links between patients occupying the same bay, the same bed space, adjacent isolation rooms and different wards. When a patient source was not identified, PFGE implicated the ward environment and the hands of staff. However, WGS disproved three of these transmission pathways. CONCLUSION: WGS can complement conventional typing methods by confirming or refuting possible MRSA transmission hypotheses. Epidemiological data are crucial in this process.

Early lesions following aerosol challenge of rhesus macaques (Macaca mulatta) with Mycobacterium tuberculosis (Erdman strain).

Three rhesus macaques (Macaca mulatta) were challenged with Mycobacterium tuberculosis (Mtb), Erdman strain, as part of studies to investigate lesion development at early time points in tuberculosis (TB) and to assess computed tomography (CT) as a method of monitoring disease progression in vivo. Animals were challenged with either a high, mid or low dose of aerosolized Mtb. The low-dose animal was killed humanely at 24 days post challenge (dpc) and the remaining animals at 25 dpc. Abnormalities in clinical parameters were observed in all animals, but clinical signs relating to respiratory disease were not seen. Pulmonary changes consistent with TB infection were detected by CT at 21 dpc and magnetic resonance imaging (MRI) post mortem. Pulmonary nodule counts obtained from both imaging techniques were directly proportional to the challenge dose and correlated with gross and microscopical lesion counts. On gross and microscopical examination, lesions of similar size and morphology were observed in the lungs of all three animals, with the majority containing necrotic foci. Concomitant gross and microscopical, granulomatous lesions were observed in the tracheobronchial lymph nodes of all animals together with evidence of systemic spread. These findings further contribute to our understanding and knowledge of early lesion formation in the lungs of non-human primates.

Helminths in the hygiene hypothesis: sooner or later?

There is increasing recognition that exposures to infectious agents evoke fundamental effects on the development and behaviour of the immune system. Moreover, where infections (especially parasitic infections) have declined, immune responses appear to be increasingly prone to hyperactivity. For example, epidemiological studies of parasite-endemic areas indicate that prenatal or early-life experience of infections can imprint an individual's immunological reactivity. However, the ability of helminths to dampen pathology in established inflammatory diseases implies that they can have therapeutic effects even if the immune system has developed in a low-infection setting. With recent investigations of how parasites are able to modulate host immune pathology at the level of individual parasite molecules and host cell populations, we are now able to dissect the nature of the host-parasite interaction at both the initiation and recall phases of the immune response. Thus the question remains - is the influence of parasites on immunity one that acts primarily in early life, and at initiation of the immune response, or in adulthood and when recall responses occur? In short, parasite immunosuppression - sooner or later?

Multi-parametric flow cytometric and genetic investigation of the peripheral B cell compartment in human type 1 diabetes.

The appearance of circulating islet-specific autoantibodies before disease diagnosis is a hallmark of human type 1 diabetes (T1D), and suggests a role for B cells in the pathogenesis of the disease. Alterations in the peripheral B cell compartment have been reported in T1D patients; however, to date, such studies have produced conflicting results and have been limited by sample size. In this study, we have performed a detailed characterization of the B cell compartment in T1D patients (n = 45) and healthy controls (n = 46), and assessed the secretion of the anti-inflammatory cytokine interleukin (IL)-10 in purified B cells from the same donors. Overall, we found no evidence for a profound alteration of the B cell compartment or in the production of IL-10 in peripheral blood of T1D patients. We also investigated age-related changes in peripheral B cell subsets and confirmed the sharp decrease with age of transitional CD19(+) CD27(-) CD24(hi) CD38(hi) B cells, a subset that has recently been ascribed a putative regulatory function. Genetic analysis of the B cell compartment revealed evidence for association of the IL2-IL21 T1D locus with IL-10 production by both memory B cells (P = 6·4 × 10(-4) ) and islet-specific CD4(+) T cells (P = 2·9 × 10(-3) ). In contrast to previous reports, we found no evidence for an alteration of the B cell compartment in healthy individuals homozygous for the non-synonymous PTPN22 Trp(620) T1D risk allele (rs2476601; Arg(620) Trp). The IL2-IL21 association we have identified, if confirmed, suggests a novel role for B cells in T1D pathogenesis through the production of IL-10, and reinforces the importance of IL-10 production by autoreactive CD4(+) T cells.

Interim estimates of 2013/14 influenza clinical severity and vaccine effectiveness in the prevention of laboratory-confirmed influenza-related hospitalisation, Canada, February 2014.

During the 2013/14 influenza season in Canada, 631 of 654 hospitalisations for laboratory-confirmed influenza enrolled in sentinel hospitals were due to Influenza A. Of the 375 with known subtype, influenza A(H1N1) accounted for 357. Interim unmatched vaccine effectiveness adjusted for age and presence of one or more medical comorbidities was determined by test-negative case-control design to be 58.5% (90% confidence interval (CI): 43.9-69.3%) overall and 57.9% (90% CI: 37.7-71.5) for confirmed influenza A(H1N1).

Cyanoacrylate tissue adhesives - effective securement technique for intravascular catheters: in vitro testing of safety and feasibility.

Partial or complete dislodgement of intravascular catheters remains a significant problem in hospitals despite current securement methods. Cyanoacrylate tissue adhesives (TA) are used to close skin wounds as an alternative to sutures. These adhesives have high mechanical strength and can remain in situ for several days. This study investigated in vitro use of TAs in securing intravascular catheters (IVC). We compared two adhesives for interaction with IVC material, comparing skin glues with current securement methods in terms of their ability to prevent IVC dislodgement and inhibit microbial growth. Two TAs (Dermabond, Ethicon Inc. and Histoacryl, B. Braun) and three removal agents (Remove™, paraffin and acetone) were tested for interaction with IVC material by use of tensile testing. TAs were also compared against two polyurethane (standard and bordered) dressings (Tegaderm™ 1624 and 1633, 3M Australia Pty Ltd) and an external stabilisation device (Statlock, Bard Medical, Covington) against control (unsecured IVCs) for ability to prevent pull-out of 16 G peripheral IVCs from newborn fresh porcine skin. Agar media containing pH-sensitive dye was used to assess antimicrobial properties of TAs and polyurethane dressings to inhibit growth of Staphylococcus aureus and Staphylococcus epidermidis. Neither TA weakened the IVCs (P >0.05). Of removal agents, only acetone was associated with a significant decrease in IVC strength (P <0.05). Both TAs and Statlock significantly increased the pull-out force (P <0.01). TA was quick and easy to apply to IVCs, with no irritation or skin damage noted on removal and no bacterial colony growth under either TA.

Genetic association of zinc transporter 8 (ZnT8) autoantibodies in type 1 diabetes cases.

AIMS/HYPOTHESIS: Autoantibodies to zinc transporter 8 (ZnT8A) are associated with risk of type 1 diabetes. Apart from the SLC30A8 gene itself, little is known about the genetic basis of ZnT8A. We hypothesise that other loci in addition to SLC30A8 are associated with ZnT8A. METHODS: The levels of ZnT8A were measured in 2,239 British type 1 diabetic individuals diagnosed before age 17 years, with a median duration of diabetes of 4 years. Cases were tested at over 775,000 loci genome wide (including 53 type 1 diabetes associated regions) for association with positivity for ZnT8A. ZnT8A were also measured in an independent dataset of 855 family members with type 1 diabetes. RESULTS: Only FCRL3 on chromosome 1q23.1 and the HLA class I region were associated with positivity for ZnT8A. rs7522061T>C was the most associated single nucleotide polymorphism (SNP) in the FCRL3 region (p = 1.13 × 10(-16)). The association was confirmed in the family dataset (p ≤ 9.20 × 10(-4)). rs9258750A>G was the most associated variant in the HLA region (p = 2.06 × 10(-9) and p = 0.0014 in family cases). The presence of ZnT8A was not associated with HLA-DRB1, HLA-DQB1, HLA-A, HLA-B or HLA-C (p > 0.05). Unexpectedly, the two loci associated with the presence of ZnT8A did not alter risk of having type 1 diabetes, and the 53 type 1 diabetes risk loci did not influence positivity for ZnT8A, despite them being disease specific. CONCLUSIONS/INTERPRETATION: ZnT8A are not primary pathogenic factors in type 1 diabetes. Nevertheless, ZnT8A testing in combination with other autoantibodies facilitates disease prediction, despite the biomarker not being under the same genetic control as the disease.