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.

Risk factors associated with short-term complications in mandibular fractures: the MANTRA study-a Maxillofacial Trainee Research Collaborative (MTReC).

INTRODUCTION: Complications following mandibular fractures occur in 9-23% of patients. Identifying those at risk is key to prevention. Previous studies highlighted smoking, age and time from injury to presentation as risk factors but rarely recorded other possible confounders. In this paper, we use a collaborative snapshot audit to document novel risk factors and confirm established risks for complications following the treatment of mandibular fractures. METHODS: The audit was carried out by 122 OMFS trainees across the UK and Ireland (49 centres) over 6 months, coordinated by the Maxillofacial Surgery Trainees Research Collaborative. Variables recorded included basic demography, medical and social history, injury mechanism and type, management and 30-day outcome. RESULTS: Nine hundred and forty-seven (947) patients with fractured mandibles were recorded. Surgical management was carried out in 76.3%. Complications at 30 days occurred 65 (9%) of those who were managed surgically. Risk factors for complications included male sex, increasing age, any medical history, increasing number of cigarettes smoked per week, increasing alcohol use per week, worse oral hygiene and increased time from injury to presentation. DISCUSSION: We have used a large prospective snapshot audit to confirm established risk factors and identify novel risk factors. We demonstrate that time from injury to presentation is confounded by other indicators of poor health behaviour. These results are important in designing trial protocols for management of mandibular fractures and in targeting health interventions to patients at highest risk of complications.

CREATE (Community deRivEd AutomaTEd insulin delivery) trial. Randomised parallel arm open label clinical trial comparing automated insulin delivery using a mobile controller (AnyDANA-loop) with an open-source algorithm with sensor augmented pump therapy in type 1 diabetes.

BACKGROUND: Commercialised automated insulin delivery (AID) systems have demonstrated improved outcomes in type 1 diabetes (T1D), however, they have limited capacity for algorithm individualisation, and can be prohibitively expensive if an individual is without access to health insurance or health funding subsidy. Freely available open-source algorithms, which have the ability to individualise algorithm parameters paired with commercial insulin pumps, and continuous glucose monitoring make up the so-called "do it yourself" (DIY) approach to AID. Limited data on the open-source approach have shown promising results, but data from a large randomised control trial are lacking. METHODS: The CREATE (Community deRivEd AutomaTEd insulin delivery) trial is an open-labelled, randomised, parallel 24-week, multi-site trial comparing sensor augmented pump therapy (SAPT) to our AnyDANA-loop. The three components of AnyDANA-loop are: 1) OpenAPS algorithm implemented in a smartphone (a version of AndroidAPS), 2) DANA-i™ insulin pump and, 3) Dexcom G6R continuous glucose monitor (CGM). The primary outcome measure is the percentage of time in target sensor glucose range (3.9 -10mmol/L). Secondary outcomes include psycho-social factors and platform performance. Analysis of online collective learning, characteristic of the open-source approach, is planned. 100 participants with T1D aged 7 - 70 years (age stratified into children/adolescents 7-15 years and adults 16-70 years), will be recruited from four sites in New Zealand. A 24-week continuation phase follows, to assess long-term safety.

A brief self-compassion intervention for adolescents with type 1 diabetes and disordered eating: a feasibility study.

AIM: To examine the feasibility and acceptability of a brief self-compassion intervention for adolescents with type 1 diabetes and disordered eating behaviour. METHODS: Twenty-seven adolescents with type 1 diabetes were recruited and randomized to receive the brief (two 2.5-h sessions) self-compassion intervention, either in the intervention group (n=11) or in a waitlist control group (n=8). The intervention was adapted from the standardized eight-session 'Making Friends with Yourself' programme, and sessions were delivered 1 week apart. Acceptability was assessed through qualitative questionnaires and feasibility was assessed based on session attendance and recruitment metrics. Possible changes to disordered eating behaviour, self-care behaviours, diabetes-related distress, self-compassion, stress and glycaemic control were also assessed. RESULTS: Nineteen participants completed the study, and they reported an increased sense of common humanity (acknowledging that we are not alone), mindfulness, and coping resources. In terms of feasibility, recruitment took longer than expected (8 months) and not all participants were able to attend both sessions (nine could only attend one of the two sessions). CONCLUSIONS: While self-compassion is a strong conceptual fit for the issues of type 1 diabetes and disordered eating behaviour in adolescence, and the intervention content appears acceptable, feasibility issues were such that brief self-compassion programmes will probably need to be adapted into digital interventions for future research. (Trial registration number: ANZCTR 12619000541101).

Partial ABCC8 gene deletion mutations causing diazoxide-unresponsive hyperinsulinaemic hypoglycaemia.

Inactivating mutations in the pancreatic beta cell ATP-sensitive potassium (K(ATP) ) channel genes are identified by sequencing in approximately 80% of patients with diazoxide-unresponsive hyperinsulinaemic hypoglycaemia (HH). Genetic testing is clinically important as the mode of inheritance of a K(ATP) channel mutation(s) provides information on the histological subtype. For example in patients with a single paternally inherited mutation a focal lesion is possible and once confirmed, the patient can undergo a curative lesionectomy. By contrast, recessive inheritance indicates diffuse disease, which requires near-total pancreatectomy, if medical management is unsuccessful. We investigated ABCC8 and KCNJ11 gene dosage in 29 probands from a cohort of 125 with diazoxide-unresponsive HH where sequencing did not provide a genetic diagnosis. We identified heterozygous partial ABCC8 deletions in four probands. In two cases with focal pancreatic disease, a paternally inherited deletion was found. Two other probands with diffuse pancreatic disease were compound heterozygotes for a deletion and a recessively acting mutation that had been identified by sequencing. Family member studies confirmed compound heterozygosity for the deletion and the missense mutation in two affected siblings of one proband. Heterozygous deletions of the ABCC8 gene are a rare, but important cause of diazoxide-unresponsive HH. Dosage analysis should be undertaken in all patients when sequencing analysis does not confirm the genetic diagnosis as confirmation of the mode of inheritance can guide clinical management and will provide important information regarding recurrence risk.

Sustainable Urban Drainage Systems (SUDS) treatment train assessment tool.

This paper outlines a rationale and scoring system for the stormwater treatment train assessment tool (STTAT) which is a proposed regulatory tool for Sustainable Urban Drainage Systems (SUDS). STTAT provides guidance and regulatory consistency for developers about the requirements of planners and the Scottish Environment Protection Agency (SEPA). The tool balances the risks of pollution to the receiving water body with the treatment provided in a treatment train. It encourages developers to take SUDS into account early, avoiding any misunderstanding of SUDS requirements at the planning stage of a development. A pessimistic view on pollution risks has been adopted since there may be a change of land use on the development in the future. A realistic view has also been taken of maintenance issues and the 'survivability' of a SUDS component. The development of STTAT as a response to the requirements of the Water Framework Directive is explored, the individual scores being given in tabular format for receiving water and catchment risks. Treatment scores are proposed for single SUDS components as well as multiple components within treatment trains. STTAT has been tested on a range of sites, predominantly in Scotland where both development and receiving water information was known. The operational tool in use by SEPA is presented.

Evidence of traffic-related pollutant control in soil-based sustainable urban drainage systems (SUDS).

SUDS are being increasingly employed to control highway runoff and have the potential to protect groundwater and surface water quality by minimising the risks of both point and diffuse sources of pollution. While these systems are effective at retaining polluted solids by filtration and sedimentation processes, less is known of the detail of pollutant behaviour within SUDS structures. This paper reports on investigations carried out as part of a co-ordinated programme of controlled studies and field measurements at soft-engineered SUDS undertaken in the UK, observing the accumulation and behaviour of traffic-related heavy metals, oil and PAHs. The field data presented were collected from two extended detention basins serving the M74 motorway in the south-west of Scotland. Additional data were supplied from an experimental lysimeter soil core leaching study. Results show that basin design influences pollutant accumulation and behaviour in the basins. Management and/or control strategies are discussed for reducing the impact of traffic-related pollutants on the aqueous environment.

Medium-term performance and maintenance of SUDS: a case-study of Hopwood Park Motorway Service Area, UK.

One of the main barriers to implementing SUDS is concern about performance and maintenance costs since there are few well-documented case-studies. This paper summarizes studies conducted between 2000 and 2008 of the performance and maintenance of four SUDS management trains constructed in 1999 at the Hopwood Park Motorway Service Area, central England. Assessments were made of the wildlife value and sedimentation in the SUDS ponds, the hydraulic performance of the coach park management train, water quality in all management trains, and soil/sediment composition in the grass filter strip, interceptor and ponds. Maintenance procedures and costs were also reviewed. Results demonstrate the benefits of a management train approach over individual SUDS units for flow attenuation, water treatment, spillage containment and maintenance. Peak flows, pond sediment depth and contaminant concentrations in sediment and water decreased through the coach park management train. Of the 2007 annual landscape budget of pounds 15,000 for the whole site, the maintenance costs for SUDS only accounted for pounds 2,500 compared to pounds 4,000 for conventional drainage structures. Furthermore, since sediment has been attenuated in the management trains, the cost of sediment removal after the recommended period of three years was only pounds 554 and, if the design is not compromised, less frequent removal will be required in future.

Ethnicity and social deprivation independently influence metabolic control in children with type 1 diabetes.

AIMS/HYPOTHESIS: This study was performed to evaluate the influence of ethnicity and socioeconomic status (SES) on metabolic control in a population-based cohort of children with type 1 diabetes mellitus, and to evaluate whether any relationship between ethnicity and HbA(1c) is mediated by SES. METHODS: We performed a retrospective review of all patients under age 16 years with type 1 diabetes (n = 555) from 1995 to 2005 in the greater Auckland region, New Zealand. Diabetes care variables and HbA(1c) values were collected prospectively, during clinic visits. RESULTS: The mean population HbA(1c) was 8.3 +/- 1.3%. Maori and Pacific patients had poorer metabolic control than their European counterparts (9.1% and 9.3% vs 8.1%, p < 0.001) and higher rates of moderate to severe hypoglycaemia (31.1 and 24.8 vs 14.9 events/100 patient-years, p = 0.03). In multiple linear regression analysis, both ethnicity and SES were independently associated with HbA(1c) (p < 0.001). Other factors associated with higher HbA(1c) level were longer duration of diabetes, higher insulin dose, lower BMI z score and less frequent blood glucose monitoring (p < 0.001). CONCLUSIONS/INTERPRETATION: Both ethnicity and SES independently influenced metabolic control in a large, unselected population of children with type 1 diabetes. Irrespective of SES, Maori and Pacific youth with type 1 diabetes were at greater risk of both moderate to severe hypoglycaemia and long-term complications associated with poor metabolic control.

A cost comparison of traditional drainage and SUDS in Scotland.

The Dunfermline Eastern Expansion (DEX) is a 350 ha mixed development which commenced in 1996. Downstream water quality and flooding issues necessitated a holistic approach to drainage planning and the site has become a European showcase for the application of Sustainable Urban Drainage Systems (SUDS). However, there is minimal data available regarding the real costs of operating and maintaining SUDS to ensure they continue to perform as per their design function. This remains one of the primary barriers to the uptake and adoption of SUDS. This paper reports on what is understood to be the only study in the UK where actual costs of constructing and maintaining SUDS have been compared to an equivalent traditional drainage solution. To compare SUDS costs with traditional drainage, capital and maintenance costs of underground storage chambers of analogous storage volumes were estimated. A whole life costing methodology was then applied to data gathered. The main objective was to produce a reliable and robust cost comparison between SUDS and traditional drainage. The cost analysis is supportive of SUDS and indicates that well designed and maintained SUDS are more cost effective to construct, and cost less to maintain than traditional drainage solutions which are unable to meet the environmental requirements of current legislation.

An angled insertion technique using 6-mm needles markedly reduces the risk of intramuscular injections in children and adolescents.

AIMS: The aims of this study were (i) to establish which children with Type 1 diabetes are at risk of intramuscular or intradermal insulin injections and (ii) to determine a needle length and technique that reliably administers insulin into subcutaneous fat. METHODS: Seventy-two healthy diabetic children (age 6.3-14.3 years, body mass index standard deviation score 1.0 +/- 1.4) were recruited for study 1 and 37 of this cohort participated in study 2. In study 1, 200 microl air was injected into the abdomen and anterior thigh by a pinched skin-fold technique using either a perpendicular insertion of NovoFine(R) 31G 6-mm or an angled insertion of NovoFine(R) 30G 8-mm needles. In study 2, subjects received injections into abdomen and anterior thigh via angled 6-mm needles with either an unpinched or pinched technique. The site of air injection was visualized by ultrasound scan and measurements taken of subcutaneous fat thickness. RESULTS: In study 1, intramuscular injections were detected in 32% of subjects, and in a further 22% air was visualized at the muscle fascia. In study 2, intramuscular injections occurred in 3% of subjects and a further 11% had muscle fascia air detected. No intramuscular injections occurred in subjects injecting with a 6-mm needle and an angled pinched skin-fold technique. Pinching abdomen and thigh skin folds increased the subcutaneous fat thickness by 192 +/- 16% and 22 +/- 6%, respectively. In very lean subjects, pinching thighs actually reduced subcutaneous fat thickness. CONCLUSIONS: While intramuscular injections were observed frequently using standard injection protocols, an angled 6-mm needle technique reliably injects into the subcutaneous fat.

Clinical phenotypes of nine cases of Kabuki syndrome from New Zealand.

Nine cases of Kabuki syndrome have been identified in Auckland and surrounding regions in the North Island, New Zealand since 1995. All have the characteristic facial dysmorphism and many of the well-described associated anomalies. Some of the abnormalities were unusual including a case with severe congenital mitral stenosis, two cases of eventration of the diaphragm, idiopathic thrombocytopaenic purpura and vitiligo. One child had an Arnold Chiari type 1 malformation and another had epibulbar dermoids, neither of which has previously been reported in this syndrome. There was a wide diversity of ethnic origin, with the syndrome being described in patients from the Pacific Islands for the first time. The cases described emphasize the broad range of associated anomalies found in Kabuki syndrome and further illustrate its presence in all ethnic groups.

Mal (MyD88-adapter-like) is required for Toll-like receptor-4 signal transduction.

The recognition of microbial pathogens by the innate immune system involves Toll-like receptors (TLRs), which recognize pathogen-associated molecular patterns. Different TLRs recognize different pathogen-associated molecular patterns, with TLR-4 mediating the response to lipopolysaccharide from Gram-negative bacteria. All TLRs have a Toll/IL-1 receptor (TIR) domain, which is responsible for signal transduction. MyD88 is one such protein that contains a TIR domain. It acts as an adapter, being involved in TLR-2, TLR-4 and TLR-9 signalling; however, our understanding of how TLR-4 signals is incomplete. Here we describe a protein, Mal (MyD88-adapter-like), which joins MyD88 as a cytoplasmic TIR-domain-containing protein in the human genome. Mal activates NF-kappaB, Jun amino-terminal kinase and extracellular signal-regulated kinase-1 and -2. Mal can form homodimers and can also form heterodimers with MyD88. Activation of NF-kappaB by Mal requires IRAK-2, but not IRAK, whereas MyD88 requires both IRAKs. Mal associates with IRAK-2 by means of its TIR domain. A dominant negative form of Mal inhibits NF-kappaB, which is activated by TLR-4 or lipopolysaccharide, but it does not inhibit NF-kappaB activation by IL-1RI or IL-18R. Mal associates with TLR-4. Mal is therefore an adapter in TLR-4 signal transduction.

Transactivation by the p65 subunit of NF-kappaB in response to interleukin-1 (IL-1) involves MyD88, IL-1 receptor-associated kinase 1, TRAF-6, and Rac1.

We have examined the involvement of components of the interleukin-1 (IL-1) signaling pathway in the transactivation of gene expression by the p65 subunit of NF-kappaB. Transient transfection of cells with plasmids encoding wild-type MyD88, IL-1 receptor-associated kinase 1 (IRAK-1), and TRAF-6 drove p65-mediated transactivation. In addition, dominant negative forms of MyD88, IRAK-1, and TRAF-6 inhibited the IL-1-induced response. In cells lacking MyD88 or IRAK-1, no effect of IL-1 was observed. Together, these results indicate that MyD88, IRAK-1, and TRAF-6 are important downstream regulators of IL-1-mediated p65 transactivation. We have previously shown that the low-molecular-weight G protein Rac1 is involved in this response. Constitutively active RacV12-mediated transactivation was not inhibited by dominant negative MyD88, while dominant negative RacN17 inhibited the MyD88-driven response, placing Rac1 downstream of MyD88 on this pathway. Dominant negative RacN17 inhibited wild-type IRAK-1- and TRAF-6-induced transactivation, and in turn, dominant negative IRAK-1 and TRAF-6 inhibited the RacV12-driven response, suggesting a mutual codependence of Rac1, IRAK-1, and TRAF-6 in regulating this pathway. Finally, Rac1 was found to associate with the receptor complex via interactions with both MyD88 and the IL-1 receptor accessory protein. A pathway emanating from MyD88 and involving IRAK-1, TRAF-6, and Rac1 is therefore involved in transactivation of gene expression by the p65 subunit of NF-kappaB in response to IL-1.

Rac1 regulates interleukin 1-induced nuclear factor kappaB activation in an inhibitory protein kappaBalpha-independent manner by enhancing the ability of the p65 subunit to transactivate gene expression.

We have examined the involvement of Rac1 in nuclear factor kappaB (NFkappaB) activation by interleukin 1 (IL1). IL1 induced a rapid and sustained activation of Rac1 in the thymoma cell line EL4.NOB-1. Transient transfection with dominant negative RacN17 inhibited IL1-induced kappaB-dependent reporter gene expression but not IkappaBalpha degradation, whereas constitutively active RacV12 potentiated kappaB-dependent reporter gene expression in response to IL1 but had no effects on its own. Using porcine aortic endothelial cells stably transfected with RacV12 or RacN17 under the control of an inducible promoter, we confirmed that RacV12 did not affect IkappaBalpha degradation, nor did RacN17 inhibit the IL1-induced response. RacV12 was also unable to induce nuclear translocation of NFkappaB. These effects suggested a role for Rac1 in p65-mediated transactivation of NFkappaB, independent of IkappaBalpha regulation. In support of this we found that IL1 activated a pathway leading to increased p65 transactivation activity and that RacV12 alone could drive this response in both cell systems. Additionally, RacN17 inhibited IL1-driven p65-mediated transactivation. From data using specific inhibitors of p38 and p42/p44 kinases we propose that both p38 and p42/p44 lie downstream of Rac1 on the IL1 pathway leading to enhanced transactivation by p65.

Meningococcal disease in Auckland, July 1992 - June 1994.

AIMS: To assess two years of meningococcal disease in the Auckland area, the outcomes and management issues, and the specific socio-geographic groups that are affected. METHODS: Using the nationally agreed case definition, a retrospective chart review was undertaken. Case finding was through the National surveillance system at ESR, backed by hospital laboratory and coroner case findings. RESULTS: There were 106 cases of meningococcal disease, both adult and paediatric, from July 1992 to June 1994. Group B (n=61), was predominant throughout this period especially in the winter months. There were two main age groups most affected. The first, and most striking, was in Maori and New Zealand Pacific Island children younger than five years, with rates of 52.6 and 54.2/100,000 respectively. The second peak was in European, and to a lesser extent Maori, 15-24 year-olds, (rates 11.7 and 8.5/100,000, respectively). The annual incidence was 5.6/100,000 with an overall case fatality rate of 6.6%, (n=7). South Auckland had the greatest proportion of cases with 42/106. Two-thirds of the cases were referred for hospital admission by a general practitioner. From both general practitioner and self-referred groups, two-thirds had a petechial/purpuric rash on arrival at hospital. For general practitioner referred cases, 24 received parenteral antibiotics on referral, and from these cases there was one death, (1/24). Those not treated with antibiotics (general practitioner or self-referred) had a mortality of 2/41. There were 31 cases of paediatric meningococcal meningitis. Nineteen cases had dexamethasone in appropriate dose and timing; no hearing loss occurred in the 17 cases that survived (0/17), compared to 2/12 not treated with dexamethasone. This compares to a published rate of 5-7%. CONCLUSIONS: Meningococcal disease, predominantly serogroup B, is of high incidence in Auckland. The highest rates of disease are occurring in the under five-year-olds, where an effective group B vaccine is awaited. The benefit of dexamethasone is suggestive. There was no clear benefit in outcome by pre-treatment with parenteral antibiotics for paediatric meningococcal disease though no suggestive detrimental effect either.

Meningococcal disease epidemiology and control in New Zealand.

Epidemiology, surveillance and research New Zealand has a high quality surveillance system for meningococcal disease that successfully integrates notification and laboratory data. Since 1991, New Zealand has had elevated incidence rates of meningococcal disease rising to 6.2 per 100,000 population in 1994. This represents a rate that is four times that recorded in 1989/90. Serogroup B infection predominates and international experience suggests that these elevated rates may continue for 5 to 15 years. Rates of meningococcal disease in Maori and Pacific Islands populations were three times higher than in Europeans at 10.0 and 12.3 per 100,000 respectively in 1994. The rates were particularly high for infants with the rate in Maori infants under 1 year reaching 120 per 100,000. The case fatality rate at 5.3% for 1994 would appear to be relatively low by international standards. Case control studies could be used to investigate potentially modifiable primary risk factors for disease. Intensive case review studies to investigate the role of such factors as preadmission antibiotics in reducing severe outcomes may be of benefit. The Ministry of Health or research funding organisations should consider the potential value of such studies in more detail.