Lessons from the use of telemedicine in the austere military environment and the implications for deployed surgical teams.

Over the last 20 years, there have been significant changes in UK surgical training. Civilian surgical training may no longer prepare military surgeons for the range of skills they require on operations. One method to address gaps in knowledge or experience is to use telemedicine to facilitate specialist consultations from UK-based specialists to deployed medical teams. In the UK Defence Medical Services (DMS), this capability is called real-time clinical support (RTCS). RTCS provides a direct audio-visual link from a deployed location anywhere in the world to a supporting medical specialist in the UK. RTCS is currently delivered via a combination of off-the-shelf hardware and commercially available software. This article will outline the current use of RTCS, with emphasis on deployed surgical teams in austere environments, and discuss the advantages and limitations of this capability. However, it must be emphasised that no technology can be a substitute for clinical training and experience. Although several limitations remain, the authors believe that RTCS offers potential benefits for the DMS and could be an important tool aiding deployed clinicians. It can also be argued that by engaging with the concept now, the DMS can shape future developments in this sphere.

Surgical outcomes for chronic exertional compartment syndrome following improved diagnostic criteria.

INTRODUCTION: Chronic exertional compartment syndrome (CECS) presents with pain during exercise, most commonly within the anterior compartment of the lower limb. A diagnosis is classically made from a typical history and the measurement of intramuscular compartmental pressure (IMCP) testing. Improved, more specific diagnostic criteria for IMCP testing allow clinicians to now be more certain of a diagnosis of CECS. Outcomes following surgical treatment in patients diagnosed using these more robust criteria are unknown. METHODS: All patients undergoing fasciectomy for anterior compartment CECS at a single rehabilitation unit were identified between 2014 and 2017. Wilcoxen signed-rank test was used to compare military fitness grading and paired t-test was used to compare Foot and Ankle Ability Measure, FAAM Sport Specific and Exercise-Induced LimbPain-G outcome measures, presurgery and postsurgery. RESULTS: There was a significant difference in fitness grading between presurgical and postsurgical intervention (Z = -2.68, p < 0.01) with 46 % of patients improving their occupational medical grading. All secondary measures of outcome, looking at clinical symptoms, also improved. CONCLUSION: Almost half of the patients undergoing fasciectomy, following diagnosis using more specific criteria, will have an improvement in occupational medical grading. These outcomes represent the lower end of those reported in civilian populations. This is likely a result of a combination of factors, most notably the different diagnostic criteria followed and the more stringent criteria applied to military occupational grading, compared with civilian practice. Further work is now required to evaluate the impact of differing rehabilitation regimes on postoperative patients identified through this more specific diagnostic testing.

'Modern' distal femoral locking plates allow safe, early weight-bearing with a high rate of union and low rate of failure: five-year experience from a United Kingdom major trauma centre.

AIMS: Fractures of the distal femur can be challenging to manage and are on the increase in the elderly osteoporotic population. Management with casting or bracing can unacceptably limit a patient's ability to bear weight, but historically, operative fixation has been associated with a high rate of re-operation. In this study, we describe the outcomes of fixation using modern implants within a strategy of early return to function. PATIENTS AND METHODS: All patients treated at our centre with lateral distal femoral locking plates (LDFLP) between 2009 and 2014 were identified. Fracture classification and operative information including weight-bearing status, rates of union, re-operation, failure of implants and mortality rate, were recorded. RESULTS: A total of 127 fractures were identified in 122 patients. The mean age was 72.8 years (16 to 101) and 92 of the patients (75%) were female. A consultant performed the operation in 85 of the cases, (67%) with the remainder performed under direct consultant supervision. In total 107 patients (84%) were allowed to bear full weight immediately. The rate of clinical and radiological union was 81/85 (95%) and only four fractures of 127 (3%) fractures required re-operation for failure of surgery. The 30-day, three- and 12-month mortality rates were 6 (5%), 17 (15%) and 25 (22%), respectively. CONCLUSION: Our study suggests an exponential increase in the incidence of a fracture of the distal femur with age, analogous to the population suffering from a proximal femoral fracture. Allowing immediate unrestricted weight-bearing after LDFLP fixation in these elderly patients was not associated with failure of fixation. There was a high rate of union and low rate of re-operation. Cite this article: Bone Joint J 2017;99-B:951-7.

Trauma-related amputations in war and at a civilian major trauma centre-comparison of care, outcome and the challenges ahead.

The Afghanistan conflict has resulted in a large number of service personnel sustaining amputations. Whilst obvious differences exist between military and civilian trauma-related amputations both settings result in life changing injuries. Comparisons offer the potential of advancement and protection of the knowledge gained during the last 12 years. This paper compares the military and civilian trauma-related amputee cohorts' demographics, management and rehabilitation outcomes measures. The UK military Joint Theatre Trauma Registry and a civilian major trauma centre database of trauma-related amputees were analysed. 255 military and 24 civilian amputees were identified. A significant difference (p>0.05) was seen in median age (24, range 18-43, vs. 48, range 24-87 years), mean number of amputations per casualty (1.6±SD 0.678 vs. 1±SD 0.0), mean ISS (22±SD 12.8 vs. 14.7±SD 15.7) and gender (99% males vs. 78%). Rehabilitation outcome measures recorded included the Special Interest Group in Amputee Medicine score where the military group demonstrated significantly better scores (91% Grade E+ compared to 19%). Differences in patients underlying physiology and psychology, the military trauma system and a huge sustained investment in rehabilitation are all contributing factors for these differing outcomes. However the authors also believe that the use of a consultant-led MDT and central rehabilitation have benefited the military cohort in the acute rehabilitation stage and is reflected in the good short-term outcomes.

Effects of frozen and liquid hypothermic storage and extender type on calcium homeostasis in relation to viability and ATP content in striped bass (Morone saxatilis) sperm.

The effect of hypothermic storage on striped bass sperm calcium homeostasis was determined by Fluo-3 flow cytometry. Calcium homeostasis was defined as the ability of cells to maintain a low concentration of intracellular free calcium as measured by Fluo-3 fluorescence. Sperm were stored frozen in striped bass extender (SBE) and Tris-NaCl medium (T350) modified with 50 mM glycine and 7.5% dimethylsulfoxide and in nonfrozen form diluted 1:3 (vol/vol) in SBE and T350 for 1, 24, and 48 hours at 4 °C in an oxygen atmosphere. Fluo-3 fluorescence was detected in less than 5% of fresh viable sperm cells indicating maintenance of calcium homeostasis. In contrast to sperm in fresh semen, frozen-thawed and nonfrozen sperm cells lost to a considerable extent the ability to maintain low intracellular free calcium even in the absence of exogenous calcium; positive Fluo-3 fluorescence was found in 26% and 39% of thawed sperm frozen in SBE- and T350-based freezing diluents, respectively, and increased (P < 0.05) to 67% during nonfrozen storage in SBE and T350 at 24 and 48 hours. Sperm viability measured by exclusion of propidium iodide by flow cytometry was 99% in fresh milt and maintained at 86% (P > 0.05) in SBE after 48 hours of nonfrozen storage but decreased (P < 0.05) to 55.7% after 48 hours in T350. Energy status in terms of ATP content, determined by luciferin-luciferase bioluminescence assay, was higher (P < 0.05) in sperm frozen in SBE than in T350 during the first 5 minutes post-thaw and decreased to essentially zero by 15 minutes post-thaw and did not differ among nonfrozen storage treatments. In conclusion, sperm cells impervious to propidium iodide after frozen or nonfrozen storage were unable to maintain low intracellular calcium content. SBE is a better medium than T350 for frozen or nonfrozen storage of striped bass sperm. The inability to regulate intracellular calcium in striped bass sperm may be associated with poor activation of motility after 4 °C storage and cryopreservation.

From model to molecules: the development and experimental manipulation of an in vivo contaminated extremity war wound.

Wound infection is a key determinant of outcome in survivors of armed conflict. One factor having potential for promoting healing, decreasing bacterial burden and influencing prognosis is the dressing that covers the ballistic-injured extremity. Although antiseptic and silver dressings are applied to acute wounds, evidence to support their use is scarce with no controlled studies reported of antimicrobial wound dressings in extremity trauma. Given the recent burden of ballistic extremity injury, the requirement to investigate the role of antimicrobial dressings in contaminated wounds is transparent. This paper details a programme of work undertaken at the Defence Science and Technology Laboratory of developing and trialling a recovery model to investigate the early management of contaminated war wounds. A New Zealand White rabbit flexor carpi ulnaris muscle belly, isolated and then injured by a drop rig mechanism, was contaminated with Staphylococcus aureus to provide a reproducible contaminated muscle wound. This model was developed to support a series of randomised controlled trials to determine the impact of antimicrobial dressings on decreasing the bacterial burden of combat related extremity wounds. The results of the initial trial indicated that over a 48-h period, dressings augmented with antiseptic or silver offer no advantage over saline-soaked gauze in reducing the bacterial burden of a contaminated soft tissue injury. The model has subsequently been used to investigate the efficacy of dressings over a 7-day study period and impact of antibiotics and to evaluate biofilm formation and wound cytokines.

Improved sperm cryosurvival in diluents containing amides versus glycerol in the Przewalski's horse (Equus ferus przewalskii).

Two studies were conducted to understand sperm cryosensitivity in an endangered equid, the Przewalski's horse (Equus ferus przewalski), while testing the cryoprotectant ability of formamides. The first assessed the toxicity of permeating cryoprotectants (glycerol, methylformamide [MF] and dimethylformamide [DMF]) to Przewalski's horse spermatozoa during liquid storage at 4°C. The second examined the comparative influence of three diluents (with or without formamides) on cryosurvival of sperm from the Przewalski's versus domestic horse. When Przewalski's horse spermatozoa were incubated at 4°C in INRA 96 with differing concentrations of glycerol, MF or DMF or a combination of these amides, cells tolerated all but the highest concentration (10% v/v) of MF alone or in combination with DMF, both of which decreased (P<0.05) motility traits. There was no effect of cryoprotectants on sperm acrosomal integrity. In the cryosurvival study, average sperm motility and proportion of cells with intact acrosomes in fresh ejaculates were similar (P>0.05) between the Przewalski's (67%, 84%, respectively) and domestic (66%, 76%) horse donors. Sperm from both species were diluted in lactose-EDTA-glycerol (EQ), Botu-Crio (BOTU; a proprietary product containing glycerol and MF) or SM (INRA 96 plus 2% [v/v] egg yolk and 2.5% [v/v] MF and DMF) and then frozen over liquid nitrogen vapor. After thawing, the highest values recovered for total and progressive sperm motility, acrosomal integrity and mitochondrial membrane potential were 42.4%, 21.8%, 88.7% and 25.4CN (CN=mean JC-1 fluorescence intensity/cell on a channel number scale), respectively, in the Przewalski's and 49.3%, 24.6%, 88.9% and 25.8CN, respectively, in the domestic horse. Although sperm progressive motility and acrosome integrity did not differ (P>0.05) among treatments across species, mitochondrial membrane potential was higher (P<0.05) in both species using EQ compared to BOTU or SM media. Additionally, Przewalski's stallion sperm expressed higher (P<0.05) post-thaw total motility in BOTU and SM compared to EQ, whereas there were no differences among freezing diluents in the domestic horse. In summary, Przewalski's stallion sperm benefit from exposure to either MF or DMF as an alternative cryoprotectant to glycerol. Overt sperm quality appears similar between the Przewalski's and domestic horse, although the total motility of cells from the former appears more sensitive to certain freezing diluents. Nonetheless, post-thaw motility and acrosomal integrity values for Przewalski's horse spermatozoa mimic findings in the domestic horse in the presence of INRA 96 supplemented with 2% (v/v) egg yolk and a combined 2.5% concentration of MF and DMF.

Quasi-prospective, real-life monitoring of food craving post-bariatric surgery: comparison with overweight and normal weight women.

Food cravings are common post-bariatric surgery, suggested as predictors of relapse and weight regain, but relatively unstudied, especially in the longer term. The present study investigated the frequency and nature of food craving experiences after gastric surgery in comparison with non-surgical control participants. Participants were 21 women, 4-38 months post-surgery (mean age = 44 years, 9 following gastric banding, 12 after Roux-en-Y gastric bypass), and two comparison samples of 39 overweight dieters and 33 normal weight non-dieters. They completed a food craving record after every food craving, a daily mood assessment and a food diary over a 7-day period. Over the 299 craving episodes, savoury foods were the most commonly craved (40% of craving events), followed by chocolate (31%). Post-bariatric patients reported more and stronger cravings than normal weight non-dieters but at a similar frequency and strength to overweight dieters. Neither hunger nor negative mood distinguished the food cravings of post-bariatric patients from those of comparison participants, nor did the proportion that led to eating (58%). Food cravings should be anticipated post-bariatric surgery but no more so at 12 months post-surgery than by other overweight or obese individuals. Food cravings are not the product of extreme hunger nor do they have the connection with negative mood seen in disordered eating. In addition, the ability to fulfil cravings by eating the craved food is reduced by the surgery itself, although the duration of surgical restraint is uncertain.

The effect of freezing rate on the quality of striped bass sperm.

Several studies have been conducted in an attempt to determine the optimal freezing rate for cryopreservation of striped bass (Morone saxatilis) sperm. In this study, the effects of freezing rate (-10 °C, -15 °C, -20 °C, and -40 °C/min) on gamete quality was examined, using Sybr-14 and propidium iodide to determine viability (sperm cell membrane integrity), ATP concentration using a luciferin-luciferase bioluminescence assay, and a CEROS computer-assisted sperm analysis system to characterize striped bass sperm motion. Adult male striped bass (N = 12) were sampled once a week for 5 weeks. Collected samples were extended, cryoprotected using a 7.5% (vol/vol) dimethyl sulfoxide final concentration solution, and frozen using a Planer Kryosave controlled-rate freezer. Samples were stored in liquid nitrogen for 49 days, and sperm quality was re-evaluated after thaw (same methods). Sperm cryopreserved at -40 °C/min resulted in means for total motility (10.06%), progressive motility (7.14%), ATP concentration (0.86 pmol/10(6) cells), and sperm viability (56.5%) that were greater (P < 0.05) than those for slower cooling rates. Therefore, -40 °C/min was the optimal freezing rate (among those tested) for cryopreservation of striped bass sperm.

Effects of reactive oxygen species on sperm function.

Reactive oxygen species (ROS) formation and membrane lipid peroxidation have been recognized as problems for sperm survival and fertility. The precise roles and detection of superoxide (SO), hydrogen peroxide (HP), and membrane lipid peroxidation have been problematic, because of the low specificity and sensitivity of the established chemiluminescence assay technologies. We developed flow cytometric assays to measure SO, HP, membrane lipid peroxidation, and inner mitochondrial transmembrane potential in boar sperm. These methods were sufficiently sensitive to permit detection of early changes in ROS formation in sperm cells that were still viable. Basal ROS formation and membrane lipid peroxidation in the absence of ROS generators were low in viable sperm of both fresh and frozen-thawed boar semen, affecting less than 4% of the sperm cells on average. However, this is not the case in other species, as human, bovine, and poultry sperm have large increases in sperm ROS formation, lipid peroxidation, loss of motility, and death in vitro. Closer study of the effects of ROS formation on the relationship between sperm motility and ATP content in boar sperm was conducted using menadione (mitochondrial SO generator) and HP treatment. Menadione or HP caused an immediate disruption of motility with delayed or no decrease in sperm ATP content, respectively. Overall, the inhibitory effects of ROS on motility point to a mitochondrial-independent mechanism. The reduction in motility may have been due to a ROS-induced lesion in ATP utilization or in the contractile apparatus of the flagellum.

Modern military surgery: lessons from Iraq and Afghanistan.

The types of explosive devices used in warfare and the pattern of war wounds have changed in recent years. There has, for instance, been a considerable increase in high amputation of the lower limb and unsalvageable leg injuries combined with pelvic trauma. The conflicts in Iraq and Afghanistan prompted the Department of Military Surgery and Trauma in the United Kingdom to establish working groups to promote the development of best practice and act as a focus for research. In this review, we present lessons learnt in the initial care of military personnel sustaining major orthopaedic trauma in the Middle East.

Plenary contribution to International Conference on Boar Semen Preservation 2011. Genetic selection for freezability and its controversy with selection for performance.

Little data are available in the literature regarding freezability of boar sperm or its relationship with other traits. Existing data suggest the trait would respond favourably to selection, and information is available from other species suggesting components that might have changed. Genetic parameters are estimated for boar sperm freezability including heritability and correlations with other production traits. Sperm freezability is an ideal candidate for marker assisted-selection or selection for favourable alleles.

Historical origins and current concepts of wound debridement.

In the late 18th Century wound debridement consisted of incision of skin and deep fascia to release the swelling associated with ballistic injury, however extremity war wounds were more usually managed non-operatively or by amputation. During the First World War debridement was redefined to include excision of all non-viable and foreign material. In the modern era it has been proposed that wounds contain a zone of injured tissue which is not obviously non-viable at the initial debridement. Debridement which preserves this tissue has been described as marginal debridement. Wounds sustained in close proximity to explosions have an extensive zone of injury. Preservation of traumatised tissue may be beneficial in terms of limb salvage and limb reconstruction. Equally the complexity and contamination of these wounds, as well as the physiological frailty of the casualty, may make complete debridement in one sitting an unachievable goal. Where traumatised tissue has been left during debridement it must be reassessed at around 48 hours in order to reduce the risk of infection. Evacuation timelines and logistic infrastructure currently support serial marginal debridement but in future conflicts this may not be the case.

Initial extremity war wound debridement: a multidisciplinary consensus.

A joint meeting of the Limb Trauma and Wounds Working Groups resulted in the establishment of 29 consensus recommendations for the conduct of initial extremity war wound debridement. Pre-operative, operative and post-operative phases of debridement were considered along with wound irrigation and dressings. Wounds where a different surgical approach is required, such as superficial soft tissue wounds at one end of the spectrum and complex wounds sustained in close proximity to explosions at the other, were also discussed. The recommendations represent the consensus opinion of orthopaedic, vascular and plastic surgeons, as well as nursing officers, from across the Defence Medical Services and are intended to provide useful guidance to the deploying surgeon, regardless of their own personal experience.

Morton's neuroma: clinical testing and imaging in 76 feet, compared to a control group.

BACKGROUND: Morton's neuroma is a mechanically induced degenerative neuropathy. METHODS: We compared clinical and MRI findings in 76 feet treated operatively for Morton's neuroma and 40 feet with different pathologies (controls). RESULTS: In the 'treatment group' web space tenderness (WST) was positive in 95%, foot squeeze (SQU) in 88%, plantar percussion (PLP) in 61%, and toe tip sensation deficit (TTSD) in 67%. MRI identified neuromata in 97%. Histological examination confirmed neuroma excision in 99%. Frequency of positive tests was significantly higher in the treatment group compared to controls. MRI revealed (asymptomatic) neuromata in 10/40 (25%) feet in the control group. TTSD was similarly positive in asymptomatic and symptomatic neuromata. TTSD in association with any other test being positive, was significantly more frequent in symptomatic neuromata. CONCLUSIONS: The diagnosis of Morton's neuroma, based on clinical and imaging findings, was accurate. Positive clinical testing was more frequent in the 'treatment' group compared to the 'control' group.

Oviductal expression of avidin, avidin-related protein-2, and progesterone receptor in turkey hens in relation to sperm storage: effects of oviduct tissue type, sperm presence, and turkey line.

The sperm storage tubules (SST) of the turkey hen, which are located in the uterovaginal junction (UVJ) of the oviduct, maintain viable sperm for up to 10 wk after a single insemination. The mechanisms of this in vivo sperm storage are poorly understood. Our objective was to evaluate mRNA and protein expression of avidin and 2 avidin-associated factors, avidin-related protein-2 (AVR2) and progesterone receptor, in the oviducts of 2 different lines to determine the extent to which they were sperm responsive and tissue specific. At 38 wk of age, Hybrid Grade Maker and Converter turkey hens were artificially inseminated with diluted semen (AI) or were sham-inseminated with extender alone (SI). Forty-eight hours after insemination, total RNA was extracted from the UVJ epithelium (containing SST) and vaginal epithelium (VGE) of SI and AI hens. Real time-polymerase chain reaction data showed a clear tissue region-specific effect on gene expression in the turkey hen oviduct, with much greater (P < 0.0001) expression in the UVJ compared with VGE region for avidin and AVR2 mRNA in both lines and for progesterone receptor mRNA in the Converter line. In contrast to real-time PCR data, in situ hybridization of SI and AI tissues showed that the presence of sperm increased avidin mRNA in the SST and UVJ surface epithelium in the Converter hens. Immunohistochemistry confirmed the presence of avidin protein in the epithelium of the UVJ in both lines; however, whereas avidin protein was localized in the SST of SI-Grade Maker hens, this protein was not detected in the SST of Converter hens. The upregulation of avidin and AVR2 mRNA within the sperm storage region indicates the involvement of avidin, and perhaps avidin analogs, in the sustained storage of sperm in the SST, possibly through the binding of biotin to avidin. The absence of avidin protein in the SST and VGE of Converter hens in the presence of increased mRNA may indicate a rapid turnover of protein.

Effects of hypothermic storage on intracellular calcium, reactive oxygen species formation, mitochondrial function, motility, and plasma membrane integrity in striped bass (Morone saxatilis) sperm.

Experiments were conducted to determine the effect of hypothermic 24 h storage on striped bass sperm cell plasma membrane integrity, free intracellular Ca(2+) ([Ca(2+)](i)), mitochondrial membrane potential (ΔΨ(m)), and reactive oxygen species (ROS) formation (oxidation of hydroethidine to ethidium) as determined by flow cytometry; motion activation and ATP concentration as determined by Luciferin-Luciferase bioluminescence assay. Semen was stored for 1 or 24 h at 4 °C in an O(2) atmosphere undiluted or diluted (one volume semen with 3 volumes diluent) with T350 (20 mM TRIS base-NaCl, 350 mOsm/mL, pH 8) or with seminal plasma in the presence of various treatments. Viability (% cells excluding propidium iodide) approached 100% after 1 h storage in undiluted or diluted semen. After 1 h of storage the [Ca(2+)](i) marker, Fluo-3, was detected in only 3% of sperm cells in undiluted or diluted semen. In contrast to storage for 1 h, after 24 h the incidence Fluo-3 fluorescence intensity was increased (P < 0.05) in > 50% of the viable cells in undiluted and diluted semen along with increased cell death; the presence of 1 mM ethylene glycol tetraacetic acid (EGTA) blocked CaCl(2)-induced Fluo-3 fluorescence and cell death. Activation of sperm motility was 82% after 1 h in T350 and decreased (P < 0.05) to 30% after 24 h. However, motility activation failed in the presence of EGTA at 1 or 24 h. During storage ΔΨ(m) was not affected by storage time or treatment. In contrast, sperm ATP was greater (P < 0.05) at 1 h than at 24 h and was greater in sperm stored in diluted than undiluted form. While ROS formation was induced by menadione treatment, there was no evidence of storage-induced ROS formation in the absence of menadione. The increased [Ca(2+)](i) found after 24 h indicates a storage induced defect in the maintenance of cellular calcium homeostasis which may be detrimental to sperm activation.

Co-administration of liraglutide with insulin detemir demonstrates additive pharmacodynamic effects with no pharmacokinetic interaction.

AIM: To compare the pharmacokinetic (PK) [area under the curve (AUC0(-)24 (h), C(max))] and pharmacodynamic (PD) (AUC(GIR) 0(-)24 (h), GIR(max)) properties of single-dose insulin detemir in the presence or absence of steady-state liraglutide (1.8 mg dose) in subjects with type 2 diabetes to determine whether co-administration affected the PK and PD profiles of either therapeutic agent. METHODS: Following a 3-week washout of oral antidiabetic agents (OADs) other than metformin, PK and PD assessments during three euglycaemia clamps were conducted: day 1 following a single dose of insulin detemir alone (0.5 U/kg), day 22 after 3 weeks of once-daily liraglutide with weekly dose escalation to 1.8 mg daily, and day 36 after 2 weeks of steady-state liraglutide maintenance at the 1.8 mg dose following co-administration with a single dose of insulin detemir (0.5 U/kg). RESULTS: The study population (N = 33; age 49.6 (±8.5) years) had diabetes for an average of 6.5 (±4.1) years, BMI 33 (±6.4) kg/m², FPG 9.7 (±1.6) mmol/l and HbA1c 8.3% (±0.9). PK: The PK profiles of insulin detemir were similar with and without steady-state liraglutide. Liraglutide did not affect AUC or C(max) of insulin detemir and vice versa. The 90% confidence intervals (CIs) for ratios of insulin detemir AUC [1.03; CI (0.97, 1.09)] and C(max) [1.05; CI (0.98, 1.13)] and liraglutide AUC [0.97; CI (0.87, 1.08)] and C(max) [1.03, CI (0.93, 1.13)] were all within the no-effect boundary (0.80, 1.25) (bioequivalence criterion). A stable mean insulin detemir concentration with and without liraglutide was maintained at the end of the 24-h PK sampling period. PD: The sum of AUC(GIR) for liraglutide (1982 mg/kg) and insulin detemir (1058 mg/kg) when given alone was similar to that obtained when the two were co-administered (2947 mg/kg). No serious adverse events were reported and no adverse events led to study withdrawal. CONCLUSION: Co-administration of liraglutide 1.8 mg at steady state and insulin detemir produces an additive glucose-lowering effect without affecting the PK profile of either therapeutic agent suggesting that the addition of insulin detemir to patients treated with liraglutide will not require titration algorithms different from when insulin is added to OADs. The co-administration of insulin detemir and liraglutide was well tolerated.

Fractures of the pelvis.

High energy fractures of the pelvis are a challenging problem both in the immediate post-injury phase and later when definitive fixation is undertaken. No single management algorithm can be applied because of associated injuries and the wide variety of trauma systems that have evolved around the world. Initial management is aimed at saving life and this is most likely to be achieved with an approach that seeks to identify and treat life-threatening injuries in order of priority. Early mortality after a pelvic fracture is most commonly due to major haemorrhage or catastrophic brain injury. In this article we review the role of pelvic binders, angiographic embolisation, pelvic packing, early internal fixation and blood transfusion with regard to controlling haemorrhage. Definitive fixation seeks to prevent deformity and reduce complications. We believe this should be undertaken by specialist surgeons in a hospital resourced, equipped and staffed to manage the whole spectrum of major trauma. We describe the most common modes of internal fixation by injury type and review the factors that influence delayed mortality, adverse functional outcome, sexual dysfunction and venous thromboembolism.