ObjectiveTo evaluate the short-term efficacy and safety of methoxyflurane for the treatment of acute pain in patients presenting to an emergency department (ED) with minor trauma.MethodsSTOP! was a randomised, double-blind, multicentre, placebo-controlled study conducted at six sites in the UK. A total of 300 patients, 90 of whom were adolescent patients (age 12–17 years), were randomised 150:150 to receive either methoxyflurane via a Penthrox inhaler or placebo. The primary end point of the study was the change in pain intensity as measured using the visual analogue scale (VAS) from baseline to 5, 10, 15 and 20 min after the start of study drug inhalation. Patients were supplied with one inhaler containing 3 mL methoxyflurane or 5 mL placebo after enrolment and initial assessments. Age group (adolescent/adult) and baseline VAS score were controlled for in the statistical analyses.ResultsA total of 149 patients received methoxyflurane, and 149 patients received placebo. Demographic and baseline characteristics were comparable between the groups. Methoxyflurane reduced pain severity significantly more than placebo (p<0.0001) at all time points tested, with the greatest estimated treatment effect of −18.5 mm (adjusted change from baseline) seen at 15 min after the start of treatment. Methoxyflurane was well tolerated, with the majority of adverse reactions being mild, transient and in line with anticipated pharmacological action.ConclusionThe results of this study suggest that methoxyflurane administered via the Penthrox inhaler is an efficacious, safe, and rapidly acting analgesic.Trial registration number:NCT01420159.

Background Tranexamic acid reduces surgical bleeding and reduces death due to bleeding in patients with trauma. Meta-analyses of small trials show that tranexamic acid might decrease deaths from gastrointestinal bleeding. We aimed to assess the effects of tranexamic acid in patients with gastrointestinal bleeding. Methods We did an international, multicentre, randomised, placebo-controlled trial in 164 hospitals in 15 countries. Patients were enrolled if the responsible clinician was uncertain whether to use tranexamic acid, were aged above the minimum age considered an adult in their country (either aged 16 years and older or aged 18 years and older), and had significant (defined as at risk of bleeding to death) upper or lower gastrointestinal bleeding. Patients were randomly assigned by selection of a numbered treatment pack from a box containing eight packs that were identical apart from the pack number. Patients received either a loading dose of 1 g tranexamic acid, which was added to 100 mL infusion bag of 0•9% sodium chloride and infused by slow intravenous injection over 10 min, followed by a maintenance dose of 3 g tranexamic acid added to 1 L of any isotonic intravenous solution and infused at 125 mg/h for 24 h, or placebo (sodium chloride 0•9%). Patients, caregivers, and those assessing outcomes were masked to allocation. The primary outcome was death due to bleeding within 5 days of randomisation; analysis excluded patients who received neither dose of the allocated treatment and those for whom outcome data on death were unavailable. This trial was registered with Current Controlled Trials, ISRCTN11225767, and ClinicalTrials.gov, NCT01658124.

IntroductionAcute pain remains highly prevalent in the Emergency Department (ED) setting. This double-blind, randomized, placebo-controlled UK study investigated the efficacy and safety of low-dose methoxyflurane analgesia for the treatment of acute pain in the ED in the adult population of the STOP! trial.MethodsPatients presenting to the ED requiring analgesia for acute pain (pain score of 4–7 on the Numerical Rating Scale) due to minor trauma were randomized in a 1:1 ratio to receive methoxyflurane (up to 6 mL) or placebo (normal saline), both via a Penthrox® (Medical Developments International Limited, Scoresby, Australia) inhaler. Rescue medication (paracetamol/opioids) was available immediately upon request. Change from baseline in visual analog scale (VAS) pain intensity was the primary endpoint.Results300 adult and adolescent patients were randomized; data are presented for the adult subgroup (N = 204). Mean baseline VAS pain score was ~66 mm in both groups. The mean change from baseline to 5, 10, 15 and 20 min was greater for methoxyflurane (−20.7, −27.4, −33.3 and −34.8 mm, respectively) than placebo (−8.0, −11.1, −12.3 and −15.2 mm, respectively). The primary analysis showed a highly significant treatment effect overall across all four time points (−17.4 mm; 95% confidence interval: −22.3 to −12.5 mm; p < 0.0001). Median time to first pain relief was 5 min with methoxyflurane [versus 20 min with placebo; (hazard ratio: 2.32; 95% CI: 1.63, 3.30; p < 0.0001)]; 79.4% of methoxyflurane-treated patients experienced pain relief within 1–10 inhalations. 22.8% of placebo-treated patients requested rescue medication within 20 min compared with 2.0% of methoxyflurane-treated patients (p = 0.0003). Methoxyflurane treatment was rated ‘Excellent’, ‘Very Good’ or ‘Good’ by 77.6% of patients, 74.5% of physicians and 72.5% of nurses. Treatment-related adverse events (mostly dizziness/headache) were reported by 42.2% of patients receiving methoxyflurane and 14.9% of patients receiving placebo; none caused withdrawal and the majority were mild and transient.ConclusionThe results of this study support the evidence from previous trials that low-dose methoxyflurane administered via the Penthrox inhaler is a well-tolerated, efficacious and rapid-acting analgesic.FundingMedical Developments International (MDI) Limited and Mundipharma Research GmbH & Co.KG.Trial registrationClinicaltrials.gov identifier: NCT01420159, EudraCT number: 2011-000338-12.

These methodologies offer opportunities for further research projects studying interactions with SPs, manikins and real clinical practice.

Background Patients with palpitations and pre-syncope commonly present to Emergency Departments (EDs) but underlying rhythm diagnosis is often not possible during the initial presentation. This trial compares the symptomatic rhythm detection rate of a smartphone-based event recorder (AliveCor) alongside standard care versus standard care alone, for participants presenting to the ED with palpitations and pre-syncope with no obvious cause evident at initial consultation. Methods Multi-centre open label, randomised controlled trial. Participants ≥ 16 years old presenting to 10 UK hospital EDs were included. Participants were randomised to either (a) intervention group; standard care plus the use of a smartphone-based event recorder or (b) control group; standard care alone. Primary endpoint was symptomatic rhythm detection rate at 90 days. Trial registration number NCT02783898 ( ClinicalTrials.gov ). Findings Two hundred forty-three participants were recruited over an 18-month period. A symptomatic rhythm was detected at 90 days in 69 (n = 124; 55.6%; 95% CI 46.9–64.4%) participants in the intervention group versus 11 (n = 116; 9.5%; 95% CI 4.2–14.8) in the control group (RR 5.9, 95% CI 3.3–10.5; p < 0.0001). Mean time to symptomatic rhythm detection in the intervention group was 9.5 days (SD 16.1, range 0–83) versus 42.9 days (SD 16.0, range 12–66; p < 0.0001) in the control group. The commonest symptomatic rhythms detected were sinus rhythm, sinus tachycardia and ectopic beats. A symptomatic cardiac arrhythmia was detected at 90 days in 11 (n = 124; 8.9%; 95% CI 3.9–13.9%) participants in the intervention group versus 1 (n = 116; 0.9%; 95% CI 0.0–2.5%) in the control group (RR 10.3, 95% CI 1.3–78.5; p = 0.006). Interpretation Use of a smartphone-based event recorder increased the number of patients in whom an ECG was captured during symptoms over five-fold to more than 55% at 90 days. This safe, non-invasive and easy to use device should be considered part of on-going care to all patients presenting acutely with unexplained palpitations or pre-syncope. Funding This study was funded by research awards from Chest, Heart and Stroke Scotland (CHSS) and British Heart Foundation (BHF) which included funding for purchasing the devices. MR was supported by an NHS Research Scotland Career Researcher Clinician award.

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Introduction The undertreatment of acute pain presents a significant challenge in the Emergency Department. This post hoc subgroup analysis of a previously reported randomized controlled UK study reports the efficacy and safety of low-dose methoxyflurane analgesia in treating adolescent patients with moderate-to-severe trauma pain. Patients and methods Three hundred patients (96 in the adolescent subgroup) aged ≥12 years requiring analgesia for acute trauma pain (pain score of 4–7 on the Numerical Rating Scale) at triage were randomized 1:1 to methoxyflurane (up to 6 mL) or placebo (normal saline), both administered using a Penthrox ® inhaler. The patient could request rescue medication (paracetamol/opioids) at any time. The primary endpoint was the change from baseline in visual analog scale (VAS) pain intensity. Results Mean VAS pain score for the adolescent subgroup at baseline was ~ 61 mm. Adjusted mean change in VAS pain intensity from baseline to 5, 10, 15, and 20 minutes was −24.5, −28.1, −31.6, and −31.7 mm for methoxyflurane and −14.6, −18.8, −19.2, and −23.7 mm for placebo, with a statistically significant treatment effect in favor of methoxyflurane overall across all four time points (−9.9 mm; 95% CI: −17.4, −2.4 mm; P =0.0104). Median time to first pain relief was significantly shorter with methoxyflurane (1 minute) than placebo (3 minutes, P <0.0001). Pain relief was reported within 1–10 inhalations in 95.7% of methoxyflurane-treated patients and 64.6% of placebo-treated patients. Rescue medication was requested by two (4.3%) methoxyflurane-treated patients and three (6.3%) placebo-treated patients. Over 95% of patients, physicians, and nurses rated methoxyflurane treatment as “Excellent”, “Very Good” or “Good” compared with between 64% and 68% for placebo. The incidence of adverse events was higher with methoxyflurane (51%) than placebo (42%), mostly comprising mild/transient dizziness and headache. Conclusion This subgroup analysis shows that low-dose inhaled methoxyflurane is a rapid-acting and effective analgesic in adolescent patients presenting with moderate-to-severe trauma pain. Trial registration Clinicaltrials.gov identifier: NCT01420159, EudraCT number: 2011-000338-12.

BackgroundUnintentional injuries among 0- to 4-year-olds are a major public health problem incurring substantial NHS, individual and societal costs. However, evidence on the effectiveness and cost-effectiveness of preventative interventions is lacking.AimTo increase the evidence base for thermal injury, falls and poisoning prevention for the under-fives.MethodsSix work streams comprising five multicentre case–control studies assessing risk and protective factors, a study measuring quality of life and injury costs, national surveys of children’s centres, interviews with children’s centre staff and parents, a systematic review of barriers to, and facilitators of, prevention and systematic overviews, meta-analyses and decision analyses of home safety interventions. Evidence from these studies informed the design of an injury prevention briefing (IPB) for children’s centres for preventing fire-related injuries and implementation support (training and facilitation). This was evaluated by a three-arm cluster randomised controlled trial comparing IPB and support (IPB+), IPB only (no support) and usual care. The primary outcome was parent-reported possession of a fire escape plan. Evidence from all work streams subsequently informed the design of an IPB for preventing thermal injuries, falls and poisoning.ResultsModifiable risk factors for falls, poisoning and scalds were found. Most injured children and their families incurred small to moderate health-care and non-health-care costs, with a few incurring more substantial costs. Meta-analyses and decision analyses found that home safety interventions increased the use of smoke alarms and stair gates, promoted safe hot tap water temperatures, fire escape planning and storage of medicines and household products, and reduced baby walker use. Generally, more intensive interventions were the most effective, but these were not always the most cost-effective interventions. Children’s centre and parental barriers to, and facilitators of, injury prevention were identified. Children’s centres were interested in preventing injuries, and believed that they could prevent them, but few had an evidence-based strategic approach and they needed support to develop this. The IPB was implemented by children’s centres in both intervention arms, with greater implementation in the IPB+ arm. Compared with usual care, more IPB+ arm families received advice on key safety messages, and more families in each intervention arm attended fire safety sessions. The intervention did not increase the prevalence of fire escape plans [adjusted odds ratio (AOR) IPB only vs. usual care 0.93, 95% confidence interval (CI) 0.58 to 1.49; AOR IPB+ vs. usual care 1.41, 95% CI 0.91 to 2.20] but did increase the proportion of families reporting more fire escape behaviours (AOR IPB only vs. usual care 2.56, 95% CI 1.38 to 4.76; AOR IPB+ vs. usual care 1.78, 95% CI 1.01 to 3.15). IPB-only families were less likely to report match play by children (AOR 0.27, 95% CI 0.08 to 0.94) and reported more bedtime fire safety routines (AOR for a 1-unit increase in the number of routines 1.59, 95% CI 1.09 to 2.31) than usual-care families. The IPB-only intervention was less costly and marginally more effective than usual care. The IPB+ intervention was more costly and marginally more effective than usual care.LimitationsOur case–control studies demonstrate associations between modifiable risk factors and injuries but not causality. Some injury cost estimates are imprecise because of small numbers. Systematic reviews and meta-analyses were limited by the quality of the included studies, the small numbers of studies reporting outcomes and significant heterogeneity, partly explained by differences in interventions. Network meta-analysis (NMA) categorised interventions more finely, but some variation remained. Decision analyses are likely to underestimate cost-effectiveness for a number of reasons. IPB implementation varied between children’s centres. Greater implementation may have resulted in changes in more fire safety behaviours.ConclusionsOur studies provide new evidence about the effectiveness of, as well as economic evaluation of, home safety interventions. Evidence-based resources for preventing thermal injuries, falls and scalds were developed. Providing such resources to children’s centres increases their injury prevention activity and some parental safety behaviours.Future workFurther randomised controlled trials, meta-analyses and NMAs are needed to evaluate the effectiveness and cost-effectiveness of home safety interventions. Further work is required to measure NHS, family and societal costs and utility decrements for childhood home injuries and to evaluate complex multicomponent interventions such as home safety schemes using a single analytical model.Trial registrationCurrent Controlled Trials ISRCTN65067450 and ClinicalTrials.gov NCT01452191.FundingThe National Institute for Health Research (NIHR) Programme Grants for Applied Research programme and will be published in full inProgramme Grants for Applied Research; Vol. 5, No. 14. See the NIHR Journals Library website for further project information.