Tobacco Smoking or Nicotine Phenotype and Severity of Clinical Presentation at the Emergency Department (SMOPHED): Protocol for a Noninterventional Observational Study.

BACKGROUND: In the last few years, several nicotine products have become available as alternatives to smoking tobacco. While laboratory and limited clinical studies suggest that these devices are less toxic compared to classic tobacco cigarettes, very little is known about their epidemiological impact. Visiting the emergency department (ED) often represents the first or even the only contact of patients with the health care system. Therefore, a study conducted at the ED to assess the impact of these products on health can be reliable and reflect a real-life setting. OBJECTIVE: The aim of this noninterventional observational study (SMOPHED study) is to analyze the association between the severity of clinical presentation observed during ED visits among patients using various nicotine products and the subsequent outcomes, specifically hospitalization and mortality. METHODS: Outcomes (hospitalization and mortality in the ED) will be examined in relation to various patterns of nicotine products use. We plan to enroll approximately 2000 participants during triage at the ED. These individuals will be characterized based on their patterns of tobacco and nicotine consumption, identified through a specific questionnaire. This categorization will allow for a detailed analysis of how different usage patterns of nicotine products correlate with the clinical diagnosis made during the ED visits and the consequent outcomes. RESULTS: Enrollment into the study started in March 2024. We enrolled a total of 901 participants in 1 month (approximately 300 potential participants did not provide the informed consent to participate). The data will be analyzed by a statistician as soon as the database is completed. Full data will be published by December 2024. CONCLUSIONS: There is substantial debate about the harm reduction potential of alternative nicotine products in terms of their smoking-cessation and risk-reduction potential. This study represents an opportunity to document epidemiological data on the link between the use of different types of nicotine products and disease diagnosis and severity during an ED visit, and thus evaluate the harm reduction potential claims for these products. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/54041.

Analgesic Efficacy, Practicality and Safety of Inhaled Methoxyflurane Versus Standard Analgesic Treatment for Acute Trauma Pain in the Emergency Setting: A Randomised, Open-Label, Active-Controlled, Multicentre Trial in Italy (MEDITA).

INTRODUCTION: Inhaled low-dose methoxyflurane is approved in Europe for emergency relief of moderate-to-severe trauma-related pain in adults, but data versus active comparators are sparse. The phase IIIb Methoxyflurane in Emergency Department in ITAly (MEDITA) trial investigated the analgesic efficacy, practicality and safety of methoxyflurane versus standard analgesic treatment (SAT) for acute trauma pain. METHODS: This was a randomised, active-controlled, parallel-group, open-label trial conducted in 15 Italian emergency units. Adults with limb trauma and pain score ≥ 4 on numerical rating scale (NRS) were randomised 1:1 to inhaled methoxyflurane 3 mL or SAT [intravenously administered (IV) morphine 0.1 mg/kg for severe pain (NRS ≥ 7); IV paracetamol 1 g or IV ketoprofen 100 mg for moderate pain (NRS 4-6)]. The primary endpoint was overall change in visual analogue scale (VAS) pain intensity from baseline (time of randomisation) to 3, 5 and 10 min. Non-inferiority and superiority of methoxyflurane versus SAT were concluded if the upper 95% confidence interval (CI) for the treatment comparison (methoxyflurane-SAT) was less than 1 and less than 0, respectively. RESULTS: Between 8 February 2018 and 8 February 2019, 272 patients were randomised (136 per treatment group). A total of 270 patients (mean age 51 years; 49% male; 34% with severe pain; mean baseline VAS 67 mm) were treated and analysed for efficacy and safety. Superiority of methoxyflurane was demonstrated for moderate-to-severe pain (adjusted mean treatment difference - 5.94 mm; 95% CI - 8.83, - 3.06 mm), moderate pain (- 5.97 mm; 95% CI - 9.55, - 2.39 mm) and severe pain (- 5.54 mm; 95% CI - 10.49, - 0.59 mm). Median onset of pain relief was 9 min for methoxyflurane and 15 min for SAT. Practicality of methoxyflurane treatment was rated "Excellent", "Very Good" or "Good" by 90% of clinicians vs. 64% for SAT. Adverse events (all non-serious) were reported by 17% of methoxyflurane-treated patients and 3% of SAT-treated patients. CONCLUSION: Methoxyflurane provided superior pain relief to SAT in patients with moderate-to-severe trauma pain and may offer a simple, fast, effective non-opioid treatment option. TRIAL REGISTRATION: Trial registered with EudraCT (2017-001565-25) on 2 March 2018 and ClinicalTrials.gov (NCT03585374) on 13 July 2018. FUNDING: Mundipharma Pharmaceuticals S.r.l.

Characterization and preventability of adverse drug events as cause of emergency department visits: a prospective 1-year observational study.

BACKGROUND: Adverse drug events (ADEs) are a significant cause of emergency department (ED) visits, with a major impact on healthcare resource utilization. A multicentre observational study, aimed to describe frequency, seriousness and preventability of ADEs reported in four EDs, was performed in Sicily (Italy) over a 1-year period. METHODS: Two trained monitors for each ED supported clinicians in identifying ADEs of patients admitted to EDs between June 1st, 2013 and May 31st, 2014 through a systematic interview of patients or their caregivers and with an additional record review. A research team analyzed each case of suspected ADE, to make a causality assessment applying the Naranjo algorithm and a preventability assessment using Schumock and Thornton criteria. Absolute and percentage frequencies with 95% confidence interval (CI) and medians with interquartile ranges (IQR) were estimated. Logistic regression models were used to evaluate independent predictors of serious and certainly preventable ADEs. RESULTS: Out of 16,963 ED visits, 575 (3.4%) were associated to ADEs, of which 15.1% resulted in hospitalization. ADEs were classified as probable in 45.9%, possible in 51.7% and definite in 2.4% of the cases. Moreover, ADEs were considered certainly preventable in 12.3%, probably preventable in 58.4%, and not preventable in 29.2% of the cases. Polytherapy influenced the risk to experience a serious, as well as a certainly preventable ADE. Whilst, older age resulted an independent predictor only of serious events. The most common implicated drug classes were antibiotics (34.4%) and anti-inflammatory drugs (22.6%). ADEs due to psycholeptics and antiepileptics resulted preventable in 62.7 and 54.5% of the cases, respectively. Allergic reactions (64%) were the most frequent cause of ADE-related ED visits, followed by neurological effects (10.2%) that resulted preventable in 1.9 and 37.3% of the cases, respectively. CONCLUSION: ADEs are a frequent cause of ED visits. The commonly used antibiotics and anti-inflammatory drugs should be carefully managed, as they are widely involved in mild to severe ADEs. Polytherapy is associated with the occurrence of serious, as well as certainly preventable ADEs, while older age only with serious events. A greater sensitivity to drug monitoring programs among health professionals is needed.

Methoxyflurane Versus Standard of Care for Acute Trauma-Related Pain in the Emergency Setting: Protocol for a Randomised, Controlled Study in Italy (MEDITA).

INTRODUCTION: Low-dose methoxyflurane, administered via a hand-held inhaler, has been used for short-term pain relief in emergency medicine in Australia and New Zealand for over 40 years, and was recently approved in Europe for the rapid relief of moderate-to-severe trauma-related pain in adults. There is currently a lack of data for methoxyflurane versus active comparators, therefore this trial will investigate the efficacy and safety of inhaled methoxyflurane compared with standard of care (SoC) in the treatment of acute trauma-related pain in pre-hospital and ED settings in Italy. METHODS: MEDITA (Methoxyflurane in Emergency Department in ITAly) is a Phase IIIb, prospective, randomised, active-controlled, parallel-group, open-label, multicentre trial. A total of 272 adult patients with moderate-to-severe pain [score ≥ 4 on the Numerical Rating Scale (NRS)] due to limb trauma will be randomised 1:1 to receive 3 mL methoxyflurane (self-administered by the patient via inhalation under supervision of a trained person) or medications that currently comprise the SoC in Italy [intravenous (IV) morphine for severe pain (NRS ≥ 7); IV paracetamol or ketoprofen for moderate pain (NRS 4-6)], administered as soon as possible after randomisation. PLANNED OUTCOMES: Pain intensity will be measured using a 100-mm visual analogue scale (VAS) at baseline (time of randomisation) and at intervals up to 30 min. Time of onset of pain relief as reported by the patient and use of rescue medication will be recorded. The patient will rate the efficacy and the healthcare professional will rate the practicality of study treatment at 30 min after randomisation using a 5-point Likert scale. Adverse events will be recorded until safety follow-up at 14 ± 2 days. Vital signs will be measured at baseline, 10 and 30 min. The primary aim is to demonstrate non-inferiority of methoxyflurane versus SoC for the change in VAS pain intensity from baseline (randomisation) to 3, 5 and 10 min. TRIAL REGISTRATION: EudraCT number: 2017-001565-25. Clinicaltrials.gov identifier: NCT03585374. FUNDING: Mundipharma Pharmaceuticals srl.

Additive value of blood neutrophil gelatinase-associated lipocalin to clinical judgement in acute kidney injury diagnosis and mortality prediction in patients hospitalized from the emergency department.

INTRODUCTION: Acute kidney injury (AKI) is a common complication among hospitalized patients. The aim of this study was to evaluate the utility of blood neutrophil gelatinase-associated lipocalin (NGAL) assessment as an aid in the early risk evaluation for AKI development in admitted patients. METHODS: This is a multicenter Italian prospective emergency department (ED) cohort study in which we enrolled 665 patients admitted to hospital from the ED. RESULTS: Blood NGAL and serum creatinine (sCr) were determined at ED presentation (T0), and at: 6 (T6), 12 (T12), 24 (T24) and 72 (T72) hours after hospitalization. A preliminary assessment of AKI by the treating ED physician occurred in 218 out of 665 patients (33%), while RIFLE AKI by expert nephrologists was confirmed in 49 out of 665 patients (7%). The ED physician's initial judgement lacked sensitivity and specificity, overpredicting the diagnosis of AKI in 27% of the cohort, while missing 20% of those with AKI as a final diagnosis. CONCLUSIONS: Our study demonstrated that assessment of a patient's initial blood NGAL when admitted to hospital from the ED improved the initial clinical diagnosis of AKI and predicted in-hospital mortality. Blood NGAL assessment coupled with the ED physician's clinical judgment may prove useful in deciding the appropriate strategies for patients at risk for the development of AKI.See related commentary by Legrand et al., http://ccforum.com/content/17/2/132.