Prehospital plasma is associated with survival principally in patients transferred from the scene of injury: A secondary analysis of the PAMPer trial.

BACKGROUND: We sought to characterize if prehospital transfer origin from the scene of injury (SCENE) or from a referral emergency department (REF) alters the survival benefit attributable to prehospital plasma resuscitation in patients at risk of hemorrhagic shock. METHODS: We performed a secondary analysis of data from a recently completed prehospital plasma clinical trial. All of the enrolled patients from either the SCENE or REF groups were included. The demographics, injury characteristics, shock severity and resuscitation needs were compared. The primary outcome was a 30-day mortality. Kaplan-Meier analysis and Cox-hazard regression were used to characterize the independent survival benefits of prehospital plasma for transport origin groups. RESULTS: Of the 501 enrolled patients, the REF group patients (n = 111) accounted for 22% with the remaining (n = 390) originating from the scene. The SCENE group patients had higher injury severity and were more likely intubated prehospital. The REF group patients had longer prehospital times and received greater prehospital crystalloid and blood products. Kaplan-Meier analysis revealed a significant 30-day survival benefit associated with prehospital plasma in the SCENE group (P < .01) with no difference found in the REF group patients (P = .36). The Cox-regression verified after controlling for relevant confounders that prehospital plasma was independently associated with a 30-day survival in the SCENE group patients (hazard ratio 0.59; 95% confidence interval 0.39-0.89; P = .01) with no significant relationship found in the REF group patients (hazard ratio 1.03, 95% confidence interval 0.4-3.0). CONCLUSION: Important differences across the SCENE and REF cohorts exist that are essential to understand when planning prehospital studies. Prehospital plasma is associated with a survival benefit primarily in SCENE group patients. The results are exploratory but suggest transfer origin may be an important determinant of prehospital plasma benefit.

Impact of Factor Xa Inhibitor Reversal with Prothrombin Complex Concentrate in Patients with Traumatic Brain Injuries.

BACKGROUND: Anticoagulant use prior to trauma has been associated with increased incidence of traumatic brain injury (TBI), intracranial hemorrhage (ICH) progression, and mortality. Prothrombin complex concentrates (PCCs) are commonly used as off-label treatments for factor Xa inhibitor-associated life-threatening hemorrhage. At this time, there is no consensus regarding appropriate indication, target dose, or outcomes of PCC administration in patients presenting with traumatic ICH. This study seeks to evaluate the impact of reversal with PCC on hemorrhage progression and outcomes in patients with TBI on preinjury factor Xa inhibitors. METHODS: This single-center retrospective cohort study included patients ≥ 18 years presenting with an acute TBI of any severity on apixaban or rivaroxaban from September 1, 2016, to September 1, 2019. Patients were grouped on the basis of receipt of PCCs for reversal (i.e., reversal or no reversal). Exclusion criteria included spontaneous ICH or known coagulopathy. Propensity score matching was conducted with the following variables: age, Abbreviated Injury Scale (head) score, and Charlson Comorbidity Index score. The primary outcome was hemorrhage stability within 48 h. Secondary outcomes included degree of hemorrhage progression, in-hospital mortality, discharge disposition, and incidence of thromboembolic events. RESULTS: Of the 115 patients meeting inclusion criteria, 84 were included in the propensity score matched data set. Baseline characteristics, comorbidities, and TBI severity were similar. The majority of patients in the reversal group (35 [83.3%]) and the no reversal (NR) group (40 [95.2%]) experienced a mild TBI (admission Glasgow Coma Scale score of 14 to 15). In the reversal group, patients received 34.3 units/kg activated PCC, 30.5 units/kg four-factor PCC, or 54.9 units/kg four-factor PCC and activated PCC on average. There was no difference observed in the incidence of hemorrhage progression (10.8% NR vs. 15.0% reversal; p = 0.739) or in median change in ICH volume (0 mL NR vs. 1 mL reversal; p = 0.2199) between groups. Additionally, reversal did not affect in-hospital mortality (3 [7.1%] NR vs. 4 [9.5%] reversal; p > 0.999). One patient in the reversal group developed a deep vein thrombosis (DVT) during the hospitalization; however, this did not result in a statistically significant difference in the occurrence of DVT (p > 0.999). CONCLUSIONS: This study demonstrated that PCC used for the treatment of factor Xa inhibitor-associated ICH related to mild TBI did not significantly impact the incidence or degree of hemorrhage progression, and PCC treatment did not result in increased thromboembolic events.

Junior trainee group 'Buddy Scheme'.

The ethos of the junior trainees' group is to facilitate peer support, an important complement to pursuing our speciality of oral and maxillofacial surgery. Launched in September 2020, the Buddy Scheme enables peer-matching. Results demonstrate this scheme has successfully provided additional support for second-degree applicants. With further help from our senior colleagues, our ambition is to expand this scheme in 2021.

Three changes to reduce the loss of dual degree trainees from OMFS national specialty selection in the UK: evidence based proposals.

The training pathway for oral and maxillofacial surgery (OMFS) has remained relatively stable for around 30 years. Circumstances surrounding the training pathway have changed including the priorities of individuals considering entering OMFS training. Run-through Specialty Training (ST1) OMFS posts (which include core surgical training) are oversubscribed while direct entry to Specialty Training (ST3) OMFS specialty recruitment rounds have unfilled posts, including places declined by appointable candidates. As part of a project to refine and improve OMFS recruitment and retention, data drawn from the British Association of Oral and Maxillofacial Surgeons (BAOMS) and the OMFS National Selection administering Deanery, Health Education England South West were scrutinised. Numbers of students starting second undergraduate degrees (medicine or dentistry) to pursue an OMFS career are increasing. Of a total of 43 candidates deemed appointable at OMFS ST1 selection but not offered an available post, 16 did not subsequently apply for ST3 selection. In the period studied (2015-20), of a total of 116 unfilled ST3 posts, 39 remained vacant because appointable candidates declined the available posts (33%). Appropriate changes to the current national selection processes could help address the perceived OMFS ST recruitment problems. By increasing the number of available ST1 posts, widening the window during which appointable candidates can continue into training and increasing prior experience recognition (including creating benchmarking processes prior to ST). These three clear, fair and transparent changes could reduce the current levels of attrition.

Perceptions and work-readiness of Australian physiotherapists in cancer care: a national evaluation.

OBJECTIVES: Physiotherapy interventions can improve health outcomes for people across the cancer continuum yet little is known of the work-readiness and perceptions of physiotherapists working in cancer care. This study described perceptions of Australian physiotherapists. DESIGN: Electronic, national cross-sectional survey. SETTING: One hundred nineteen Australian hospitals and 35 rehabilitation programmes in July 2019 were invited. PARTICIPANTS: Clinical physiotherapists responsible for the provision of cancer care. MAIN OUTCOME MEASURES: Custom-designed survey targeted clinical knowledge, physiotherapy management, physical activity/exercise, and learning/preparedness. Relationships between domains and demographic characteristics eg: clinical experience and work setting, were analysed. RESULTS: One hundred twenty eight surveys were completed. Median [IQR] experience was 8 [4 to 19] years (2 [0.5 to 5] years specifically in oncology). Most participants (99/128, 77%) felt poorly prepared to commence work in oncology. Confidence was consistently lower among physiotherapists in their first year compared to others. Confidence and knowledge was rated high for people with early stage cancers (median 4 [3 to 5]) and lower for prescribing exercise for patients with cardiotoxicity and knowledge of precautions/contraindications regarding hormone and targeted therapies (median 2 [1 to 3]). High importance ratings (Likert scores 4 or 5) were reported for exercise (115/127, 91%) and physical activity (120/126, 95%). Learning needs were identified for medical management, treatment side-effects/precautions and management of cancer-related pain and fatigue. CONCLUSION: Australian physiotherapists feel underprepared to work in cancer care, but report good confidence and knowledge. Professional development opportunities appear indicated.

How can oral and maxillofacial surgery units best support second degree students?

Returning to study for a second degree to enter higher OMFS training often leaves students feeling 'out in the wilderness'. Many OMFS units are keen to support these students and make use of their skills and enthusiasm by employing them. Often there are barriers to students and units working together. We have explored some of these barriers by surveying second-degree students (both medical and dental) to see what simple measures OMFS units can take to improve their support for students. From the survey we have devised a list of Essential and Desirable criteria to assist OMFS units in supporting students, aiming to have a positive effect on retention through the challenging but necessary period of the second degree.

Junior Trainees Group (JTG) of the British Association of Oral and Maxillofacial Surgeons (BAOMS) conference 2018: overview of the conference and analysis of delegates' feedback.

The Junior Trainees Group (JTG) of the British Association of Oral and Maxillofacial Surgeons (BAOMS) and the JTG Annual Conference aim to support pre-registrar trainees interested in OMFS. The theme of the 2018 conference, "Research and Innovation" was disseminated through a diversity of expert speakers and interactive workshops. This paper provides an overview of the conference and analysis of the delegates' feedback to show how it represented their interests and influenced their decisions to pursue OMFS. Online questionnaires assessed demographics and the impact of the conference on numerous aspects of the decisions made about careers by delegates at different levels of training. A Kruskal Wallis test with post-hoc pairwise comparisons was done to assess the significance of differences between groups. A total of 135 delegates completed the questionnaires (13% dual-qualified; 13% second-degree medics; 18% second-degree dentists; 6% singly-qualified medics; 41% singly-qualified dentists; 5% first-degree medics; and 4% first-degree dentists), and 141 submitted abstracts of which 32 poster and 12 oral presentations were accepted. A total of 79/135 (59%) were members of the BAOMS. Word-of-mouth was the commonest way by which delegates became aware of the conference. As the stage of training advanced, they agreed more that it represented their training level and influenced them to pursue research and attend the BAOMS 2018 conference. The JTG conference is the only national meeting for pre-registrar trainees, and this year there were record numbers of delegates and abstracts. As the JTG grows, we continue to assist juniors to pursue their involvement in OMFS units and to participate in research and collaborative projects. Our goals are to expand as a national platform to represent junior trainees who are interested in OMFS, and to support them as they progress towards registrar training.

Disinhibited eating mediates differences in attachment insecurity between bariatric surgery candidates/recipients and lean controls.

Previous research has shown that attachment anxiety is a good predictor of body mass index. This relationship is significantly mediated by disinhibited (over-) eating and is likely to reflect a specific form of affect regulation. This study explored whether obese bariatric surgery candidates (BSC; N=34) and bariatric surgery recipients (BSR; N=15) would show higher levels of attachment insecurity (higher attachment anxiety and/or higher attachment avoidance) than a group of age and gender-matched lean controls (N=54). Mediation analyses showed that compared to lean controls (M=2.96, SE=0.1), both BSC (M=3.5, SE=0.2) and BSR (M=3.4, SE=0.2) groups had a more insecure attachment orientation. These relationships were significantly mediated by disinhibited eating (BSC: lower limit confidence interval (LLCI)=0.06 and upper limit confidence interval (ULCI)=0.62; BSR: LLCI=0.02 and ULCI=0.76). There was no such relationship when the BSC and BSR groups were compared (LLCI=-0.15 & ULCI=0.3). These observations suggest that attachment insecurity may be a risk factor for obesity and bariatric surgery because of associated disinhibited eating. Moreover, these factors may be important to consider when bariatric surgery results in poor outcomes.

Treatment of Hyponatremia in Patients with Acute Neurological Injury.

BACKGROUND: Little data exist regarding the practice of sodium management in acute neurologically injured patients. This study describes the practice variations, thresholds for treatment, and effectiveness of treatment in this population. METHODS: This retrospective, multicenter, observational study identified 400 ICU patients, from 17 centers, admitted for ≥48 h with subarachnoid hemorrhage (SAH), traumatic brain injury (TBI), intraparenchymal hemorrhage, or intracranial tumors between January 1, 2011 and July 31, 2012. Data collection included demographics, APACHE II, Glascow Coma Score (GCS), serum sodium (Na+), fluid rate and tonicity, use of sodium-altering therapies, intensive care unit (ICU) and hospital length of stay, and modified Rankin score upon discharge. Data were collected for the first 21 days of ICU admission or ICU discharge, whichever came first. Sodium trigger for treatment defined as the Na+ value prior to treatment with response defined as an increase of ≥4 mEq/L at 24 h. RESULTS: Sodium-altering therapy was initiated in 34 % (137/400) of patients with 23 % (32/137) having Na+ >135 mEq/L at time of treatment initiation. The most common indications for treatment were declining serum Na+ (68/116, 59 %) and cerebral edema with mental status changes (21/116, 18 %). Median Na+ treatment trigger was 133 mEq/L (IQR 129-139) with no difference between diagnoses. Incidence and treatment of hyponatremia was more common in SAH and TBI [SAH (49/106, 46 %), TBI (39/97, 40 %), ICH (27/102, 26 %), tumor (22/95, 23 %); p = 0.001]. The most common initial treatment was hypertonic saline (85/137, 62 %), followed by oral sodium chloride tablets (42/137, 31 %) and fluid restriction (15/137, 11 %). Among treated patients, 60 % had a response at 24 h. Treated patients had lower admission GCS (12 vs. 14, p = 0.02) and higher APACHE II scores (12 vs. 10, p = 0.001). There was no statistically significant difference in outcome when comparing treated and untreated patients. CONCLUSION: Sodium-altering therapy is commonly employed among neurologically injured patients. Hypertonic saline infusions were used first line in more than half of treated patients with the majority having a positive response at 24 h. Further studies are needed to evaluate the impact of various treatments on patient outcomes.

Risk factors for discharge on a new antipsychotic medication after admission to an intensive care unit.

PURPOSE: Increased awareness of delirium in the intensive care unit (ICU) has led to higher use of antipsychotic medications for treatment of delirium. These medications are often not discontinued at ICU or hospital discharge, which may increase the risk of inappropriate polypharmacy. Our study sought to identify risk factors for being discharged on a new antipsychotic medication after admission to a trauma-surgical ICU or neurocritical care unit. METHODS: This was a retrospective cohort study at an academic medical center and included patients who were admitted to the trauma-surgical ICU or neurocritical care unit and received an antipsychotic medication. Those younger than 18 years, died before hospital discharge, or did not have complete documentation were excluded. RESULTS: A total of 341 records were included in the final analysis. Of those, 82 (24%) were discharged on a new antipsychotic and 67% of those patients had no documented indication. Acute Physiology and Chronic Health Evaluation II (odds ratio, 1.030 [95% confidence interval, 1.030-1.110]) and days treated with benzodiazepines (odds ratio, 1.101 [95% confidence interval, 1.060-1.143]) were independently associated with being discharged on a new antipsychotic medication. CONCLUSIONS: Those patients with higher Acute Physiology and Chronic Health Evaluation II scores and more benzodiazepine days are at increased odds of being discharged on a new antipsychotic.

Gene expression analysis in RA: towards personalized medicine.

Gene expression has recently been at the forefront of advance in personalized medicine, notably in the field of cancer and transplantation, providing a rational for a similar approach in rheumatoid arthritis (RA). RA is a prototypic inflammatory autoimmune disease with a poorly understood etiopathogenesis. Inflammation is the main feature of RA; however, many biological processes are involved at different stages of the disease. Gene expression signatures offer management tools to meet the current needs for personalization of RA patients' care. This review analyses currently available information with respect to RA diagnostic, prognostic and prediction of response to therapy with a view to highlight the abundance of data, whose comparison is often inconclusive due to the mixed use of material source, experimental methodologies and analysis tools, reinforcing the need for harmonization if gene expression signatures are to become a useful clinical tool in personalized medicine for RA patients.

Seizure prophylaxis in neurocritical care: a review of evidence-based support.

Seizures are a well-described complication of acute brain injury and neurosurgery. Antiepileptic drugs (AEDs) are frequently utilized for seizure prophylaxis in neurocritical care patients. In this review, the Neurocritical Care Society Pharmacy Section describes the evidence associated with the use of AEDs for seizure prophylaxis in patients with intracerebral tumors, traumatic brain injury, aneurysmal subarachnoid hemorrhage, craniotomy, ischemic stroke, and intracerebral hemorrhage. Clear evidence indicates that the short-term use of AEDs for seizure prophylaxis in patients with traumatic brain injury and aneurysmal subarachnoid hemorrhage may be beneficial; however, evidence to support the use of AEDs in other disease states is less clear.

Clinical efficacy and safety of a water-soluble micellar paclitaxel (Paccal Vet) in canine mastocytomas.

OBJECTIVE: To determine the clinical efficacy and safety of a cremophor-free formulation of paclitaxel (Paccal Vet, Oasmia Pharmaceuticals) in dogs with mast cell tumours. METHODS: Paccal Vet was administered at a median dose of 145 (range, 135 to 150) mg/m(2) intravenously once every 21 days for three cycles to 29 dogs with macroscopic grade 2 or 3 mast cell tumour. Efficacy was assessed by tumour response (Response Evaluation Criteria in Solid Tumours version 1.0) and performance status score. Progression-free survival, quality of life and safety/adverse events were also evaluated. Clinical safety was assessed by clinicopathological analyses and recording of adverse events. RESULTS: Complete or partial response was observed in 59% of dogs. Performance status score remained constant or improved for 20 dogs and decreased by one grade for 9 dogs. Median time to progression was 247 (range, 42 to 268) days. Expected, transient frequently subclinical adverse events (primarily grade 3/4 neutropenia and grade 1/2 leukopenia) were observed in the majority of dogs. Nine dogs were euthanased and one dog died due to disease progression. CLINICAL SIGNIFICANCE: Paccal Vet appears to be a clinically safe and effective treatment for canine mast cell tumours. Further controlled confirmatory investigation is warranted.

Effect of Pauli blockade on spin-dependent diffusion in a degenerate electron gas.

Spin-polarized transport of photoelectrons in bulk, p-type GaAs is investigated in the Pauli blockade regime. In contrast to usual spin diffusion processes in which the spin polarization decreases with distance traveled due to spin relaxation, images of the polarized photoluminescence reveal a spin-filter effect in which the spin polarization increases during transport over the first 2 µm from 26% to 38%. This is shown to be a direct consequence of the Pauli principle and the associated quantum degeneracy pressure which results in a spin-dependent increase in the minority carrier diffusion constants and mobilities. The central role played by the quantum degeneracy pressure is confirmed via the observation of a spin-dependent increase in the photoelectron volume and a spin-charge coupling description of this is presented.

Novel methods of myocardial protection and de-airing for complex descending aortic aneurysm surgery.

A 64-year-old male who had previously undergone an aortic valve replacement and replacement of the ascending aorta presented with an 8 cm descending aortic aneurysm. A left thoracotomy was required to allow replacement of the aorta. However, due to longitudinal as well as transverse expansion, visualisation of the aortic arch was compromised, preventing cross-clamping of the proximal aorta. Cardiopulmonary bypass and deep hypothermic circulatory arrest were, therefore, required. An unusual method of cardioplegia delivery was used for myocardial protection, utilising a Foley catheter under direct vision as an alternative to more expensive percutaneous peripheral endoclamp devices. We also describe an unusual cardiopulmonary bypass circuit, with the dual use of a left atrial cannula for venting and also for re-establishing perfusion during de-airing.

Kavalactones Yangonin and Methysticin induce apoptosis in human hepatocytes (HepG2) in vitro.

While cases of severe kava hepatotoxicity have been reported, studies examining the toxicity of individual kavalactones are limited. The present study examined the in vitro hepatotoxicity of kavain, methysticin and yangonin on human hepatocytes (HepG2) and the possible mechanism(s) involved. Cytotoxicity was assessed using lactate dehydrogenase (LDH) and ethidium bromide (EB) assays. The mode of cell death was analysed with acridine orange/ethidium bromide dual staining with fluorescence microscopy. Glutathione oxidation was measured using the ortho-phthalaldehyde (OPT) fluorescence assay. Kavain had minimal cytotoxicity, methysticin showed moderate concentration-dependent toxicity and yangonin displayed marked toxicity with ~ 40% reduction in viability in the EB assay. Acridine orange/ethidium bromide staining showed the predominant mode of cell death was apoptosis rather than necrosis. No significant changes were observed in glutathione levels, excluding this as the primary mechanism of cell death in this model. Further studies may elucidate the precise apoptotic pathways responsible and whether toxic kavalactone metabolites are involved.

Attachment anxiety, disinhibited eating, and body mass index in adulthood.

Several studies report a relationship between body mass index (BMI) and disinhibited eating (a failure to restrict intake and to overeat). However, the aetiology of disinhibited eating has received scant attention. In this study, we consider a role for 'attachment orientation', a trait that reflects the quality of bonding in early life and remains stable throughout adulthood. Participants (N = 200, females = 135, BMI range from 17.4 to 41.1 kg m(-2)) completed measures of disinhibition and attachment orientation. 'Attachment anxiety' was a good predictor of disinhibited eating (P<0.001). Furthermore, mediation analysis confirmed that it is through this relationship that attachment anxiety also predicts BMI (P=0.02). These findings are consistent with other studies, showing an association between attachment orientation and other disinhibited behaviours, including alcohol and substance abuse. Our interpretation is that disinhibited eaters engage in external affect regulation. In doing so, they seek to mitigate the anxiety associated with poor interpersonal attachments.

Sequential microarray to identify timing of molecular responses to Haemonchus contortus infection in sheep.

Anthelmintics are currently the most common method of worm control. The emergence of worms with multiple-drug resistance and issues of residues in the food chain make alternative parasite control measures a priority. To develop improved and sustainable methods for controlling Haemonchus contortus such as genetic selection of resistant sheep, a better understanding of the host-parasite relationship is required. A trial was undertaken using sheep surgically implanted with abomasal fistulas to enable sequential biopsy of the abomasal mucosa during trickle infection with two strains of H. contortus. These were ivermectin-resistant CAVR and ivermectin-sensitive McMaster. From a gross parasitology perspective, this approach enabled the effect of developing immunity to be observed on both the establishment and maturation of two CAVR doses within and between groups. Since the only difference in parasite treatment between the groups was the staggering of the two CAVR doses, microarray results from biopsies taken on the same day in different groups were combined and compared between different biopsy dates to observe differential gene transcription over time. Differential gene transcription was detected by comparing transcription in our array data between different biopsy dates using a low P value screen (P<0.01) and by compiling a list of 82 immunoparasitology-related genes and examining transcription in this list with a higher P value screen (P<0.05). Our microarray data were validated in silico by comparison with intelectin 2, trefoil factor 3, calcium activated chloride channel and mucin 5 from other gene transcription studies and with phenotypic data such as the response by gammadelta T cells and immunoglobulins to H. contortus. The first four genes are involved in non-specific responses to infection and mucosal healing. These were upregulated at the early time points and intelectin 2 remained prominent throughout the trial. As the trial progressed, immunoglobulin genes became strongly upregulated. These included IgCgamma IgG2a heavy chain constant region, IGHE immunoglobulin heavy constant epsilon and IGHM immunoglobulin heavy constant mu.

Posterior fossa surgery complicated by a pseudomeningocele, bilateral subdural hygromata and cerebellar cognitive affective syndrome.

We report the case of a 51-year-old woman who underwent excision of a left postero-inferior, para-vermian cerebellar hemangioblastoma and foramen magnum decompression for an associated acquired Chiari I malformation. Two weeks postoperatively she developed a pseudomeningocele, bilateral supra- and infratentorial subdural hygromata, and a clinical disorder compatible with the cerebellar cognitive affective syndrome. There was no response to drainage of the left supratentorial collection. CSF aspiration from a pseudomeningocele lead to resolution of her syndrome and the subdural effusions. The relationships between the subdural hygromas, pseudomeningocele, location of the lesion within the cerebellum, cerebellar oedema, and the cause of her cognitive-affective syndrome are discussed.

Expression of p16, CD95, CD95L and Helix pomatia agglutinin in relapsing and nonrelapsing very thin melanoma.

BACKGROUND: The incidence of malignant melanoma is increasing worldwide and patients are being diagnosed earlier with thinner primary lesions. Most patients with very thin melanoma (Breslow thickness < 0.76 mm) are cured by surgery but 2-18% relapse locally or with distant metastases. OBJECTIVES: The objective of this study was to establish potential new prognostic markers in very thin melanoma. METHODS: We identified a group of subjects with relapsing very thin primary cutaneous melanoma and a matched control group who had not relapsed. We investigated the expression of p16, Helix pomatia agglutinin (HPA), CD95 and CD95 ligand (CD95L) by immunohistochemistry on paraffin-embedded tissue sections from the subject group, their subsequent metastases and the control group. RESULTS: Reduced p16 expression was significantly associated with relapse in very thin melanoma (P = 0.0129). Loss of p16 expression was also found in 76% of metastases. There was no significant association between HPA, CD95 or CD95L expression and subsequent relapse. CONCLUSIONS: This work is the first to show a significant loss of p16 in relapsing very thin melanoma.