Conectar
Pain accounts for approximately 80% of emergency department admissions. While intravenous morphine titration is commonly used for severe pain, non-invasive alternatives that bypass intravenous access are needed. Nebulised fentanyl, combined with pupillometry for objective monitoring of opioid impregnation, may offer a rapid and safe alternative for pain management.
This phase I, open-label, randomised, exploratory, crossover, single-centre prospective controlled trial will employ pharmacokinetic–pharmacodynamic (PK–PD) modelling to assess the variability in bioavailability of nebulised fentanyl administered via intranasal route versus facial aerosol. 20 healthy volunteers will receive three repeated administrations of fentanyl over two visits. At each visit, blood samples (n=11) will be collected for fentanyl quantification by liquid chromatography–tandem mass spectrometry, and pupillary unrest in ambient light (PUAL) measurements (n=9) will be recorded. The resulting data will be analysed using Monolix 2024R1 to model PK–PD relationships, perform Monte Carlo simulations and determine the optimal dosing and timing required to achieve a reduction of more than 30% in PUAL, while also evaluating safety, comfort and tolerance.
The study has been approved by the Ethic Committee Île-de-France VII (approval reference number: 000216, February 2024) and will be conducted in accordance with the Declaration of Helsinki. Informed consent will be obtained from all participants. Study findings will be disseminated through peer-reviewed publications, conference presentations and appropriate data-sharing platforms to support further research and clinical application.
This trial is registered at ClinicalTrials.gov (Identifier: NCT06281951).
Radiotherapy is recommended for G2-G3 large soft tissue sarcoma in association with radical wide excision in order to improve the local control of disease, but side-effects may develop early after radiation invalidating wound healing. We retrospective evaluated short- and long-term clinically relevant outcomes after surgery of limb STS with or without radiotherapy. All 243 patients with limb STS treated at the Veneto Institute Oncology (Padua, Italy) in 2015–2022 were retrospectively included. Outcome measures were short- and long-term wound complications, length of hospital stay and outpatient care time. Multivariable analyses were performed using linear regression models and logistic regression models. Overall, 87 patients received neoadjuvant radiotherapy, 64 received adjuvant radiotherapy and 92 underwent surgery alone. At short-term, multivariable analysis identified neoadjuvant radiotherapy as a risk factor for prolonged length of hospital stay (MD 6.4 days, 95%CI 3.9 to 9.0 days) and short-term wound complications (OR 3.45, 95%CI 1.82 to 6.62). At long-term, neoadjuvant radiotherapy was a risk factor for long-term wound complications (OR 4.87, 95%CI 2.48 to 9.84), and longer outpatient care time (MD 83 days, 95%CI 41 to 126 days); similarly, adjuvant radiotherapy was also a risk factor for long-term complications (OR 5.20, 95%CI 2.57 to 10.95) and longer outpatient care time (MD 62 days, 95%CI 19 to 106 days). Radiotherapy in limb STS was associated with impaired short- and long-term clinically relevant outcomes, potentially affecting quality of life and healthcare costs. Balancing with its well-known oncological benefits, new clinical strategies are needed to contain cutaneous radiogenic side effects. The use of negative pressure therapy can play a key role in the prevention of wound complications in oncological patients.
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