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Whether prehospital administration of tranexamic acid increases the likelihood of survival with a favorable functional outcome among patients with major trauma and suspected trauma-induced coagulopathy who are being treated in advanced trauma systems is uncertain. We randomly assigned adults with major trauma who were at risk for trauma-induced coagulopathy to receive tranexamic acid (administered intravenously as a bolus dose of 1 g before hospital admission, followed by a 1-g infusion over a period of 8 hours after arrival at the hospital) or matched placebo. The primary outcome was survival with a favorable functional outcome at 6 months after injury, as assessed with the use of the Glasgow Outcome Scale-Extended (GOS-E). Levels on the GOS-E range from 1 (death) to 8 (\"upper good recovery\" [no injury-related problems]). We defined survival with a favorable functional outcome as a GOS-E level of 5 (\"lower moderate disability\") or higher. Secondary outcomes included death from any cause within 28 days and within 6 months after injury. A total of 1310 patients were recruited by 15 emergency medical services in Australia, New Zealand, and Germany. Of these patients, 661 were assigned to receive tranexamic acid, and 646 were assigned to receive placebo; the trial-group assignment was unknown for 3 patients. Survival with a favorable functional outcome at 6 months occurred in 307 of 572 patients (53.7%) in the tranexamic acid group and in 299 of 559 (53.5%) in the placebo group (risk ratio, 1.00; 95% confidence interval [CI], 0.90 to 1.12; P = 0.95). At 28 days after injury, 113 of 653 patients (17.3%) in the tranexamic acid group and 139 of 637 (21.8%) in the placebo group had died (risk ratio, 0.79; 95% CI, 0.63 to 0.99). By 6 months, 123 of 648 patients (19.0%) in the tranexamic acid group and 144 of 629 (22.9%) in the placebo group had died (risk ratio, 0.83; 95% CI, 0.67 to 1.03). The number of serious adverse events, including vascular occlusive events, did not differ meaningfully between the groups. Among adults with major trauma and suspected trauma-induced coagulopathy who were being treated in advanced trauma systems, prehospital administration of tranexamic acid followed by an infusion over 8 hours did not result in a greater number of patients surviving with a favorable functional outcome at 6 months than placebo. (Funded by the Australian National Health and Medical Research Council and others; PATCH-Trauma ClinicalTrials.gov number, NCT02187120.).

The study examined the influence of physical location on survival from out-of-hospital cardiac arrest (OHCA). Firstly, OHCAs occurring in residential settings were compared to those occurring in public locations. Secondly, the residential OHCAs were classified according to socioeconomic status and the relationship between socioeconomic status and outcome from OHCA was examined. For all OHCAs that occurred between 1 July 2007 and 30 June 2010, we compared OHCA characteristics and outcomes between public and residential locations, and for residential locations examined across deciles of socioeconomic status. Of the 445 arrests that occurred during the study period, 413 met the inclusion criteria. Survival from OHCA in public locations was approximately twice that for residential OHCA (19.8% vs 10.7%, p=0.021). We found no association between survival from residential OHCA and socioeconomic status. Similarly, we found no association between socioeconomic status and witnessing of the event, bystander cardiopulmonary resuscitation, the initial presenting rhythm, and ambulance response time. Residential OHCA in the Wellington region has a much poorer prognosis than OHCA in public locations. There is no evidence to suggest that any socioeconomic group in the Wellington region is disadvantaged when a community and ambulance response is required for an OHCA.

A prospective analysis was undertaken of the workload of prehospital triage and treatment facilities established in Wellington for the 2011 and 2012 International Rugby Sevens, and the Rugby World Cup 2011 (RWC). The introduction of an alcohol intoxication pathway, the impact of the initiative on ambulance and Emergency Department (ED) workload, and its cost effectiveness were assessed. A log of patients seen and their diagnoses and treatment was maintained. An alcohol questionnaire was completed when applicable. Patients intoxicated with alcohol were managed in accordance with a flowchart designed for paramedic use. Costs and savings were calculated. Half the patients were New Zealanders. The average age was 25 years with a slight female preponderance (52.9% female). 30% were students. Alcohol was a contributory or causative factor for the patient's attendance in 80-90% of cases. Approximately 60% of the 121 patients seen at the last two events would have had to be transferred to the ED in the absence of the treatment centre. Cost savings for the ambulance service and ED for the RWC and 2012 Sevens are estimated to be NZ$70,000. No adverse clinical event was identified. With minimal supervision, event medics and paramedics can safely care for the majority of patients attending large rugby events in New Zealand, easing the pressure on ambulances and the ED, and generating significant cost savings for those services.

The key features of this model are: * The appointment of Extended Care Paramedics (ECPs) to assess and treat patients in their homes and local communities * Improved patient experience, especially for the elderly and those with mobility problems * Avoidance of unnecessary transfer to hospital4,5 as well as a reduction in the numbers of patients with minor conditions having to wait longer for treatment in the ED * More effective allocation of emergency ambulances and improved response times for potentially life-threatening conditions To assist in achieving their goals, ECPs require ready access to appropriate local care pathways. Sarah R Hoyle, Executive Manager Clinical Services, Wellington Free Ambulance, Wellington; Andrew W Long, Executive Manager Strategic Development and Improvement, Wellington Free Ambulance, Wellington Acknowledgement: The authors and Wellington Free ambulance acknowledge the financial support given by Capital & Coast DHB to enable this pilot project to be established and wish to thank clinical staff in Kapiti District and Wellington Hospital ED for their kind support.

Analyses and compares survival rates from community cardiac arrest in the Wellington region with similar data reported nationally and internationally. Studies in particular the impact of a dual fire and ambulance service response. Source: National Library of New Zealand Te Puna Matauranga o Aotearoa, licensed by the Department of Internal Affairs for re-use under the Creative Commons Attribution 3.0 New Zealand Licence.

States the case for extending regulation under the Health Practitioners Competence Assurance Act 2003 (HPCA) to cover ambulance paramedics who administer emergency care. Source: National Library of New Zealand Te Puna Matauranga o Aotearoa, licensed by the Department of Internal Affairs for re-use under the Creative Commons Attribution 3.0 New Zealand Licence.

Up to 20% of Primary Biliary Cholangitis (PBC) patients are estimated to have features that overlap with Autoimmune Hepatitis (AIH). Patients with PBC-AIH overlap syndrome (PBC-AIH OS) have been reported to exhibit suboptimal responses to ursodeoxycholic acid therapy, and are more likely to progress to cirrhosis. Anti-double stranded DNA (anti-dsDNA) and anti-p53 have been previously suggested to be potential autoantibodies for identifying patients with PBC-AIH OS. In our well defined PBC patient cohorts, a comprehensive assessment of various classical and novel autoantibodies was evaluated for their utility in identifying PBC-AIH OS patients. PBC-AIH OS was classified according to the Paris criteria and PBC as per the European Association for the Study of the Liver guidelines. Biobanked serum samples from 197 patients at the University of Calgary Liver Unit and the University of Alberta were analyzed for classical and novel autoantibodies. Anti-dsDNA was measured by the Crithidia luciliae immunofluorescence (CLIFT) assay (1:20 dilution) and chemiluminescence (CIA: QUANTA Flash®, Inova Diagnostics, San Diego). Anti-p53, anti-Ro52/TRIM21, anti-YB 1, anti-GW182, anti-Ge-1, and anti-Ago 2 were measured by either an addressable laser bead immunoassay (ALBIA) or line immunoassay (LIA). Autoantibodies against MIT3, gp210, sp100, LKM1, SLA, and the novel autoantibodies Hexokinase-1 (HK-1), and Kelch like protein 12 (KLHL-12) were measured using QUANTA Lite® ELISA assays. We applied non-parametric methods to compare the biomarkers frequencies between study groups. We used multivariate adjusted models and AUROC to compare the diagnostic accuracy of the different autoantibodies alone or in combination with serum biochemistry. 16 out of 197 PBC patients (8.1%) were classified as PBC-AIH OS. Compared to PBC patients, PBC-AIH OS patients were similar in age (median: 59 vs. 63, P = 0.21) and female predominance (94% vs. 89%, P = 1.00). Anti-dsDNA-by CLIFT (37.5% in PBC-AIH OS vs 9.9% in PBC alone, P <0.01) was the only autoantibody associated with PBC-AIH OS; a finding consistent with previous reports. Significant elevation in serum ALT (62 IU/L in PBC-AIH OS vs 37 IU/L in PBC alone, P < 0.01), and serum IgG (17.6 g/L in OS vs 12.1 g/L in PBC alone, P <0.01) were observed in patients with PBC-AIH OS receiving medical/immunosuppressive therapy. In a multivariate model, positive anti-dsDNA by CLIFT, ALT and IgG were significant predictors of PBC-AIH OS with an area under the receiver operator curve (AUROC) value of 0.84. Consistent with previous findings, the presence of anti-dsDNA by CLIFT is associated with PBC-AIH OS. Contrary to previous reports, anti-p53 was not associated with PBC-AIH OS. Our comprehensive evaluation of various classical and novel autoantibody biomarkers including Ro52/TRIM21, anti-p53, anti-KLHL-12 and anti-HK-1 were not significantly associated with PBC-AIH OS. Our findings highlight the ongoing need for the research and development of new autoantibody biomarkers to aid in the diagnosis of PBC-AIH OS.

Tissue-resident memory T cells (T RM ) protect from repeat infections within organs and barrier sites. The breadth and duration of such protection are defined at minimum by three quantities: the rate at which new T RM are generated from precursors, their rate of self-renewal, and their rate of loss through death, egress, or differentiation. Quantifying these processes individually is challenging. Here we combine genetic fate mapping tools and mathematical models to untangle these basic homeostatic properties of CD4 + T RM in the skin and gut lamina propria (LP) of healthy adult mice. We show that CD69 + CD4 + T RM in skin reside for ∼24 days and self-renew more slowly, such that clones halve in size approximately every 5 weeks, and approximately 2% of cells are replaced daily from precursors. CD69 + CD4 + T RM in LP have shorter residencies (∼14 days) and are maintained largely by immigration (4–6% per day). We also find evidence that the continuous replacement of CD69 + CD4 + T RM at both sites derives from circulating effector-memory CD4 + T cells, in skin possibly via a local CD9 − intermediate. Our approach maps the ontogeny of CD4 + T RM in skin and LP and exposes their dynamic and distinct behaviours, with continuous seeding and erosion potentially impacting the duration of immunity at these sites.

AbstractObjectiveTo determine the association between high flow supplementary oxygen and 30 day mortality in patients presenting with a suspected acute coronary syndrome (ACS).DesignPragmatic, cluster randomised, crossover trial.SettingFour geographical regions in New Zealand.Participants40 872 patients with suspected or confirmed ACS included in the All New Zealand Acute Coronary Syndrome Quality Improvement registry or ambulance ACS pathway during the study periods. 20 304 patients were managed using the high oxygen protocol and 20 568 were managed using the low oxygen protocol. Final diagnosis of ST elevation myocardial infarction (STEMI) and non-STEMI were determined from the registry and ICD-10 discharge codes.InterventionsThe four geographical regions were randomly allocated to each of two oxygen protocols in six month blocks over two years. The high oxygen protocol recommended oxygen at 6-8 L/min by face mask for ischaemic symptoms or electrocardiographic changes, irrespective of the transcapillary oxygen saturation (SpO2). The low oxygen protocol recommended oxygen only if SpO2 was less than 90%, with a target SpO2 of less than 95%.Main outcome measure30 day all cause mortality determined from linkage to administrative data.ResultsPersonal and clinical characteristics of patients managed under both oxygen protocols were well matched. For patients with suspected ACS, 30 day mortality for the high and low oxygen groups was 613 (3.0%) and 642 (3.1%), respectively (odds ratio 0.97, 95% confidence interval 0.86 to 1.08). For 4159 (10%) patients with STEMI, 30 day mortality for the high and low oxygen groups was 8.8% (n=178) and 10.6% (n=225), respectively (0.81, 0.66 to 1.00) and for 10 218 (25%) patients with non-STEMI was 3.6% (n=187) and 3.5% (n=176), respectively (1.05, 0.85 to 1.29).ConclusionIn a large patient cohort presenting with suspected ACS, high flow oxygen was not associated with an increase or decrease in 30 day mortality.Trial registrationANZ Clinical Trials ACTRN12616000461493.