32 research outputs found

    Evaluation of pre-hospital use of a valsalva assist device in the emergency treatment of supraventricular tachycardia [EVADE]: a randomised controlled feasibility trial

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    Background: The valsalva manoeuvre is an internationally recommended initial treatment for supraventricular tachycardia (SVT). The pre-hospital use of a valsalva assist device, to help deliver this manoeuvre, could improve cardioversion rates and reduce the need for patients to attend hospital. Methods: We conducted a randomised controlled feasibility trial comparing ambulance clinician use of a valsalva assist device versus standard care to treat adult patients presenting to an ambulance service in the south west of England. Eligible consenting participants were randomised 1:1 to device or standard care with trial procedures mirroring a proposed definitive trial.Feasibility was assessed upon ambulance clinician and participant recruitment rates and feedback, data completeness and potential future primary outcome rates. Results: Over a 6 months period (1 July to 31 December 2018), 276 (23%) of 1183 eligible ambulance clinicians were trained and they recruited 34 participants; approximately 10% of patients presenting with suspected SVT during that time. Seventeen participants were randomised to each arm and all underwent their allocated valsalva strain method. All trial data and 63/68 (93%) of pre and post-valsalva ECGs were available. Seven (21%) participants had ineligible initial rhythms on retrospective expert ECG review. Valsalva assist device use was associated with cardioversion and non-conveyance in 4 (24%) and 2 (12%) participants respectively. No participants assigned to standard care were cardioverted and all were conveyed. Participant feedback highlighted the challenges of retaining trial information during an SVT attack. Conclusions: The trial achieved efficient clinician training, randomisation and data collection, and there was an encouraging effect signal associated with device use. However, trial design changes should be considered to address the relatively small proportion of eligible patients recruited and challenges identified with consent and confirmation of cardioversion as a primary outcome. Trial registration: The trial was registered with ClinicalTrials.gov (NCT03514628) on 2 May 2018.This article is freely available via Open Access. Click on the Publisher URL to access it via the publisher's site.The study was funded by a grant from SWASFT (Ref: 16-019) from research capacity funding provided by the National Institute for Health Research (NIHR)published version, accepted versio

    Dexibuprofen nanocrystals with improved therapeutic performance: fabrication, characterization, in silico modeling, and in vivo evaluation

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    Naseem Ullah,1 Shahzeb Khan,1 Shaimaa Ahmed,2 Thirumala Govender,2 Hani S Faidah,3 Marcel de Matas,4 Muhammad Shahid,5 Muhammad Usman Minhas,6 Muhammad Sohail,7 Muhammad Khurram8 1Department of Pharmacy, University of Malakand, Chakdara, Pakistan; 2Discipline of Pharmaceutical Sciences, School of Health Sciences, University of KwaZulu-Natal, Durban, South Africa; 3Department of Microbiology, Faculty of Medicine, Umm Al Qura University, Makkah, Kingdom of Saudi Arabia; 4SEDA Pharmaceutical Development Services, The BioHub at Alderley Park, Cheshire, UK; 5Department of Pharmacy, Sarhad University of Science and Information Technology, Peshawar, Pakistan; 6Faculty of Pharmacy and Alternative Medicine, The Islamia University of Bahawalpur, Punjab, Pakistan; 7Department of Pharmacy, COMSATS, Abbottabad, Pakistan; 8Department of Pharmacy, Shaheed Benazir Bhutto University, Sheringal, Pakistan Background: The aim of this study was to prepare and evaluate the impact of polymers on fabricating stable dexibuprofen (Dexi) nanocrystals with enhanced therapeutic potential, using a low energy, anti-solvent precipitation method coupled with molecular modelling approach. Methods: Dexi nanocrystals were prepared using antisolvent precipitation with syringe pump. Crystallinity of the processed Dexi particles was confirmed using differential scanning calorimetry and powdered X-ray diffraction and transmission electron microscopy. Dissolution of Dexi nanocrystals was compared with raw Dexi and marketed tablets. Molecular modelling study was coupled with experimental studies to rationalise the appropriate polymers for stable Dexi nanocrystals. Antinociceptive study was carried out using balb mice. Results: Combinations of hydroxypropyl methylcellulose (HPMC)–polyvinyl pyrrolidone (PVP) and HPMC–Eudragit (EUD) were shown to be very effective in producing stable Dexi nanocrystals with particle sizes of 85.0±2.5 nm and 90±3.0 nm, and polydispersity of 0.179±0.01, 0.182±0.02, respectively. The stability studies conducted for 90 days demonstrated that nanocrystals stored at 2°C–8°C and 25°C were more stable than those at 40°C. The maximum recovery of Dexi nanocrystals was observed from the formulations using the combination of HPMC–PVP and HPMC–EUD, which equated to 98% and 94% of the nominal active drug content respectively. The saturation solubility of the Dexi nanocrystals was substantially increased to 270.0±3.5 µg/mL compared to the raw Dexi in water (51.0±2.0 µg/mL) and stabilizer solution (92.0±3.0 µg/mL). Enhanced dissolution rate (P<0.05) was observed for the Dexi nanocrystals compared to the unprocessed drug substance and marketed tablets. Dexi nanocrystals produced the analgesic effect at much lower doses (5 mg/kg) than that of control standard, diclofenac sodium (20 mg/kg) and Dexi counterparts (40 mg/kg). Conclusion: HPMC-PVP and HPMC-EUD were found the best polymer combination to stabilise Dexi nanocrystals. The Dexi nanocrystals exhibited significant dissolution, solubility and analgesic effect compared to the raw Dexi and the control standard diclofenac sodium. Keywords: dexibuprofen, nanocrystals, dissolution, antinociceptive activity, molecular modeling, stabilit
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