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The Untrained Public's Ability to Apply the Layperson Audiovisual Assist Tourniquet vs a Combat Application Tourniquet: A Randomized Controlled Trial
Goolsby C, Jonson CO, Goralnick E, Dacuyan-Faucher N, Schuler K, Kothera C, Shah A, Cannon J, Prytz E
Journal of the American College of Surgeons. 2022
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Editor's Choice
Abstract
BACKGROUND While the Stop the Bleed (STB) campaign's impact is encouraging, gaps remain. These gaps include rapid skill decay, a lack of easy-to-use tourniquets for the untrained public, and training barriers that prevent scalability. A team of academic and industry partners developed the Layperson Audiovisual Assist Tourniquet (LAVA TQ) - the first audiovisual-enabled tourniquet for public use. LAVA TQ addresses known tourniquet application challenges and is novel in its design and technology. METHODS This study is a prospective, randomized, superiority trial comparing the ability of the untrained public to apply LAVA TQ to a simulated leg versus their ability to apply a Combat Application Tourniquet (CAT). The study team enrolled participants in Boston, Maryland, and Sweden in 2022. The primary outcome was the proportion of successful applications of each tourniquet. Secondary outcomes included: mean time to application, placement position, reasons for failed application, and comfort with the devices. RESULTS Participants applied the novel LAVA TQ successfully 93% (n=66 of 71) of the time compared to 22% (n=16 of 73) success applying CAT [RR 4.24 95% CI (2.74-6.57)] (P < 0.001). Participants applied LAVA TQ faster (74.1s) compared to CAT (126s) (P <0.001) and experienced a greater gain in comfort using LAVA TQ than CAT. CONCLUSION The untrained public is four times more likely to apply LAVA TQ correctly than CAT. The public also applies LAVA TQ faster than CAT and has more favorable opinions about its usability. LAVA TQ's highly intuitive design and built-in audiovisual guidance solve known problems of layperson education and skill retention and could improve public bleeding control.
PICO Summary
Population
Untrained members of the public (n= 147).
Intervention
Layperson Audiovisual Assist Tourniquet (LAVA TQ), (n= 73)
Comparison
Combat Application Tourniquet (CAT), (n= 74).
Outcome
Participants applied the novel LAVA TQ successfully 93% (n= 66 of 71) of the time compared to 22% (n= 16 of 73) success applying CAT [relative risk: 4.24 95% CI (2.74-6.57)]. Participants applied LAVA TQ faster (74.1 seconds) compared to CAT (126 seconds) and experienced a greater gain in comfort using LAVA TQ than CAT.
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Intravenous iron to treat anaemia following critical care: a multicentre feasibility randomised trial
Shah A, Chester-Jones M, Dutton SJ, Marian IR, Barber VS, Griffith DM, Singleton J, Wray K, James T, Drakesmith H, et al
British journal of anaesthesia. 2021
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Editor's Choice
Abstract
BACKGROUND Anaemia is common and associated with poor outcomes in survivors of critical illness. However, the optimal treatment strategy is unclear. METHODS We conducted a multicentre, feasibility RCT to compare either a single dose of ferric carboxymaltose 1000 mg i.v. or usual care in patients being discharged from the ICU with moderate or severe anaemia (haemoglobin ≤100 g L(-1)). We collected data on feasibility (recruitment, randomisation, follow-up), biological efficacy, and clinical outcomes. RESULTS Ninety-eight participants were randomly allocated (49 in each arm). The overall recruitment rate was 34% with 6.5 participants recruited on average per month. Forty-seven of 49 (96%) participants received the intervention. Patient-reported outcome measures were available for 79/93 (85%) survivors at 90 days. Intravenous iron resulted in a higher mean (standard deviation [sd]) haemoglobin at 28 days (119.8 [13.3] vs 106.7 [14.9] g L(-1)) and 90 days (130.5 [15.1] vs 122.7 [17.3] g L(-1)), adjusted mean difference (10.98 g L(-1); 95% confidence interval [CI], 4.96-17.01; P<0.001) over 90 days after randomisation. Infection rates were similar in both groups. Hospital readmissions at 90 days post-ICU discharge were lower in the i.v. iron group (7/40 vs 15/39; risk ratio=0.46; 95% CI, 0.21-0.99; P=0.037). The median (inter-quartile range) post-ICU hospital stay was shorter in the i.v. iron group but did not reach statistical significance (5.0 [3.0-13.0] vs 9.0 [5.0-16.0] days, P=0.15). CONCLUSION A large, multicentre RCT of i.v. iron to treat anaemia in survivors of critical illness appears feasible and is necessary to determine the effects on patient-centred outcomes. CLINICAL TRIAL REGISTRATION ISRCTN13721808 (www.isrctn.com).
PICO Summary
Population
Patients being discharged from the intensive care unit (ICU) with moderate or severe anaemia (n= 98).
Intervention
Single dose of ferric carboxymaltose (n= 49).
Comparison
Usual care (n= 49).
Outcome
Patient-reported outcome measures were available for 85% survivors at 90 days. Intravenous iron resulted in a higher mean (standard deviation [sd]) haemoglobin at 28 days (119.8 [13.3] vs. 106.7 [14.9] g L(-1)) and 90 days (130.5 [15.1] vs. 122.7 [17.3] g L(-1)), adjusted mean difference (10.98 g L(-1)) over 90 days after randomisation. Infection rates were similar in both groups. Hospital readmissions at 90 days post-ICU discharge were lower in the intravenous iron group (7/40 vs. 15/39). The median (inter-quartile range) post-ICU hospital stay was shorter in the intravenous iron group but did not reach statistical significance (5.0 [3.0-13.0] vs. 9.0 [5.0-16.0]) days.
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Direct comparison of two extended half-life PEGylated recombinant FVIII products: a randomized, crossover pharmacokinetic study in patients with severe hemophilia A
Solms A, Shah A, Berntorp E, Tiede A, Iorio A, Linardi C, Ahsman M, Mancuso ME, Zhivkov T, Lissitchkov T
Annals of hematology. 2020
Abstract
An open-label, crossover randomized study was performed to compare the pharmacokinetics (PK) of damoctocog alfa pegol and rurioctocog alfa pegol, two recombinant factor VIII (FVIII) products indicated in patients with hemophilia A, both conjugated to polyethylene glycol to reduce clearance and extend time in circulation. Adult patients (N = 18) with severe hemophilia A (FVIII < 1 IU/dL), previously treated with any FVIII product for ≥ 150 exposure days, were randomized to receive a single 50 IU/kg infusion of damoctocog alfa pegol followed by rurioctocog alfa pegol, or vice versa, with ≥ 7-day washout between doses. FVIII activity was measured using the one-stage clotting assay. PK parameters, including area under the curve from time 0 to the last data point (AUC(0-tlast), primary parameter), dose-normalized AUC (AUC(norm)), and time to threshold, were calculated based on 11 time points between 0.25 and 120 h post-dose and evaluated using a noncompartmental model. Due to differences in batch-specific vial content used for the study, actual administered median doses were 54.3 IU/kg for damoctocog alfa pegol and 61.4 IU/kg for rurioctocog alfa pegol. Based on actual dosing, a significantly higher geometric mean (coefficient of variation [%CV]) AUC(norm) was observed for damoctocog alfa pegol (43.8 h kg/dL [44.0]) versus rurioctocog alfa pegol (36.0 h kg/dL [40.1, P < 0.001]). Based on population PK modeling, median time to reach 1 IU/dL was 16 h longer for damoctocog alfa pegol compared with rurioctocog alfa pegol. No adverse events or any immunogenicity signals were observed. Overall, damoctocog alfa pegol had a superior PK profile versus rurioctocog alfa pegol. Trial registration number: NCT04015492 ( ClinicalTrials.gov identifier). Date of registration: July 9, 2019.
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Direct comparison of two extended-half-life recombinant FVIII products: a randomized, crossover pharmacokinetic study in patients with severe hemophilia A
Shah A, Solms A, Wiegmann S, Ahsman M, Berntorp E, Tiede A, Iorio A, Mancuso ME, Zhivkov T, Lissitchkov T
Annals of hematology. 2019
Abstract
BAY 94-9027 is an extended-half-life, recombinant factor VIII (rFVIII) product conjugated with a 60-kDa branched polyethylene glycol (PEG) molecule indicated for use in previously treated patients (aged ≥ 12 years) with hemophilia A. This randomized, open-label, two-way crossover study compared the pharmacokinetics (PK) of BAY 94-9027 and rFVIII Fc fusion protein (rFVIIIFc) in patients with hemophilia A. Patients aged 18-65 years with FVIII < 1% and ≥ 150 exposure days to FVIII were randomized to receive intravenous single-dose BAY 94-9027 60 IU/kg followed by rFVIIIFc 60 IU/kg or vice versa, with ≥ 7-day wash-out between doses. FVIII activity was measured by one-stage assay. PK parameters, including area under the curve from time 0 to the last data point (AUClast, primary parameter), half-life, and clearance were calculated. Eighteen patients were randomized and treated. No adverse events were observed. In the analysis set excluding one outlier, geometric mean (coefficient of variation [%CV, 95% confidence interval {CI}]) AUClast was significantly higher for BAY 94-9027 versus rFVIIIFc (2940 [37.8, 2440-3550] IU h/dL versus 2360 [31.8, 2010-2770] IU h/dL, p = 0.0001). A population PK model was developed to simulate time to reach FVIII threshold levels; median time to 1 IU/dL was approximately 13 h longer for BAY 94-9027 versus rFVIIIFc after a single infusion of 60 IU/kg. In conclusion, BAY 94-9027 had a superior PK profile versus rFVIIIFc. ClinicalTrials.gov : NCT03364998.
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Improved pharmacokinetics with BAY 81-8973 versus antihemophilic factor (Recombinant) plasma/albumin-free method: a randomized pharmacokinetic study in patients with severe hemophilia A
Shah A, Solms A, Garmann D, Katterle Y, Avramova V, Simeonov S, Lissitchkov T
Clinical Pharmacokinetics. 2016;56((9):):1045-1055
Abstract
BACKGROUND BAY 81-8973 is a full-length, unmodified, recombinant human factor VIII (FVIII) for the treatment of hemophilia A. OBJECTIVE The aim of this study was to compare the pharmacokinetic (PK) profile of BAY 81-8973 with antihemophilic factor (recombinant) plasma/albumin-free method (rAHF-PFM) PATIENTS/METHODS In this phase I, open-label, crossover study, men aged 18-65 years with severe hemophilia A and ≥150 exposure days to FVIII were randomized to receive a single intravenous infusion of 50 IU/kg BAY 81-8973 or rAHF-PFM, followed by crossover to a single infusion of the other treatment. FVIII levels were measured in plasma over 48 h using one-stage and chromogenic assays. PK parameters, including area under the curve from time zero to the last data point (AUClast; primary outcome) and half-life (t (1/2)) were calculated. A population PK model was developed to simulate various treatment scenarios. RESULTS Eighteen patients were randomized and analyzed. Using both assays, geometric mean (coefficient of variation [%CV]) AUClast was significantly higher, and t (1/2) was significantly longer, for BAY 81-8973 versus rAHF-PFM (one-stage, AUClast: 1660 IU.h/dL [29.4] vs. 1310 IU.h/dL [29.0], p < 0.0001; one-stage, t (1/2): 14.5 [25.7] vs. 11.7 h [27.3], p < 0.0001). Simulations showed that median time to 1 IU/dL was approximately 27% longer for BAY 81-8973 versus rAHF-PFM over doses of 25-50 IU/kg; plasma levels >1 IU/dL could be maintained with 14.4 IU/kg BAY 81-8973 or 39.1 IU/kg rAHF-PFM 3x/week. CONCLUSIONS BAY 81-8973 showed a superior PK profile versus rAHF-PFM. The same FVIII trough threshold level could be achieved with lower doses of BAY 81-8973 versus rAHF-PFM. ClinicalTrials.gov: NCT02483208.
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Clinical benefits of two different dosing schedules of recombinant human erythropoietin in anemic patients with advanced head and neck cancer
Gupta S, Singh PK, Bhatt ML, Pant MC, Sundar S, Verma J, Paul S, Kumar D, Shah A, Gupta R, et al
Bioscience Trends. 2010;4((5):):267-72.
Abstract
A total of 100 patients with stage III or IV head or neck cancer, a performance status of 0-1, and anemia with hemoglobin (Hb) < 10 g/dL at baseline who where to receive chemotherapy concomitantly or sequentially with radiotherapy were randomized to receive either epoetin beta 10,000 IU thrice weekly (TW) (n = 52) and oral iron starting 10-15 days before the start of treatment or epoetin beta 30,000 IU once weekly (OW) (n = 48) and oral iron before the start of treatment. The mean Hb in patients on the thrice weekly (11. 96 g/dL) and once weekly (12. 50 g/dL) dosing schedules increased significantly (p < 0. 01) at the end of the treatment in comparison to respective baseline values of 9. 38 g/dL and 9. 41 g/dL; levels were 1. 2-fold higher, which was significant (p < 0. 01), for patients on the once weekly schedule. That said, there was significant improvement (p < 0. 01) in mean linear analog scale assessment (LASA) scores for energy level (EL), ability to perform daily activities (AL), and overall quality of life (QOL) for patients on both dosing schedules but these improvements did not differ significantly between schedules (p > 0. 05). The 2-year overall survival for patients on both dosing schedules did not differ significantly (p > 0. 05). Epoetin beta therapy was found to be equally beneficial and well tolerated for patients on both thrice weekly and once weekly dosing schedules.