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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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Efficacy and Safety of Intravenous Iron Therapy for Treating Anaemia in Critically ill Adults: A Rapid Systematic Review With Meta-Analysis
Geneen LJ, Kimber C, Doree C, Stanworth S, Shah A
Transfusion medicine reviews. 2021
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Editor's Choice
Abstract
Our objective was to systematically evaluate the efficacy and safety of intravenous (IV) iron therapy for treating anaemia in critically ill adults (>16 years) admitted to intensive care or high dependency units. We excluded quasi-RCTs and other not truly randomised trials. We searched 7 electronic databases (including CENTRAL, MEDLINE, and Embase) using a pre-defined search strategy from inception to June 14, 2021. One reviewer screened, extracted, and analysed data, with verification by a second reviewer of all decisions. We used Cochrane risk of bias (ROB) 1 and GRADE to assess the certainty of the evidence. We reported 3 comparisons across 1198 patients, in 8 RCTs: (1) IV iron vs control (7 RCTs, 748 participants); our primary outcome (hemoglobin (Hb) concentration at 10 to 30 days) was reported in 7 of the 8 included trials. There was evidence of an effect (very-low certainty) in favour of IV iron over control in the main comparison only (6 RCTs, n = 528, mean difference (MD) 0.52g/dL [95%CI 0.23, 0.81], P = .0005). For the remaining outcomes there was no evidence of an effect in either direction (low certainty of evidence for Hb concentration at <10 days; very-low certainty of evidence for hospital duration, ICU duration, hospital readmission, infection, mortality; HRQoL outcomes were not GRADED). (2) IV iron + subcutaneous erythropoietin (EPO) vs control (2 RCTs, 104 participants); reported outcomes showed no evidence of effect in either direction, based on very-low certainty evidence (Hb concentration at 10-30 days, and <10 days, infection, mortality). (3) Hepcidin-guided treatment with IV iron or iron+ EPO vs standard care (1 RCT, 399 participants) reported evidence of an effect in favour of the intervention for 90-day mortality (low certainty of evidence), but no other group differences for the reported outcomes (low certainty evidence for Hb concentration at 10-30 days, hospital duration; HRQoL was not GRADED). The evidence across all comparisons was downgraded for high and unclear ROB for lack of blinding, incomplete outcome data, baseline imbalance, and imprecision around the estimate (wide CIs and small sample size). In conclusion, the current evidence continues to support further investigation into the role for iron therapy in increasing Hb in critically ill patients. Recent, small, trials have begun to focus on patient-centred outcomes but a large, well conducted, and adequately powered trial is needed to inform clinical practice.
PICO Summary
Population
Critically ill adults admitted to intensive care or high dependency units (8 studies, n= 1,198).
Intervention
Intravenous (IV) iron therapy; IV iron and subcutaneous erythropoietin (EPO); Hepcidin and targeted IV iron treatment (with and without EPO).
Comparison
Placebo/no iron therapy, or EPO therapy; Standard care.
Outcome
Seven trials (n= 748) comparing IV vs. control, found evidence of an effect in favour of IV iron in the main comparison only (6 RCTs, n = 528, mean difference (MD) 0.52g/dL). There was no evidence of an effect in either direction for hospital duration, intensive care unit duration, hospital readmission, infection, and mortality. For the two trials (n= 104) comparing IV iron and subcutaneous erythropoietin (EPO) vs. control, the reported outcomes showed no evidence of effect in either direction (Hb concentration at 10-30 days, and <10 days, infection, mortality). One trial (n= 399) comparing hepcidin-guided treatment with IV iron or iron and EPO vs. standard care reported evidence of an effect in favour of the intervention for 90-day mortality, but no other group differences for Hb concentration at 10-30 days, hospital duration, and HRQoL.
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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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Endovascular Coiling Versus Neurosurgical Clipping for Aneurysmal Subarachnoid Hemorrhage: A Systematic Review and Meta-analysis
Ahmed SI, Javed G, Bareeqa SB, Samar SS, Shah A, Giani A, Aziz Z, Tasleem A, Humayun SH
Cureus. 2019;11(3):e4320
Abstract
Background Aneurysmal subarachnoid hemorrhage is a frequently devastating condition with a reported incidence of between 10 and 15 people per 100,000 in the United States. Currently, according to the best of our knowledge, there are not enough meta-analyses available in the medical literature of the last five years which compare the risks and benefits of endovascular coiling with neurosurgical clipping. Methods Twenty-two studies were selected out of the short-listed studies. The studies were selected on the basis of relevance to the topic, sample size, sampling technique, and randomization. Data were analyzed on Revman software. Results Mortality was found to be significantly higher in the endovascular coiling group (odds ratio (OR): 1.17; confidence interval (CI): 95%, 1.04, 1.32). Re-bleeding was significantly higher in endovascular coiling (OR: 2.87; CI: 95%, 1.67, 4.93). Post-procedure complications were significantly higher in neurosurgical clipping compared to endovascular coiling (OR: 0.36; CI: 95%, 0.24, 0.56). Neurosurgical clipping was a 3.82 times better surgical technique in terms of re-bleeding (Z = 3.82, p = 0.0001). Neurosurgical clipping is a better technique requiring fewer re-treatments compared to endovascular coiling (OR: 4.64; CI: 95%, 2.31, 9.29). Endovascular coiling was found to be a better technique as it requires less rehabilitation compared to neurosurgical clipping (OR: 0.75; CI: 95%, 0.64,0.87). Conclusion Neurosurgical clipping provides better results in terms of mortality, re-bleeding, and re-treatments. Endovascular coiling is a better surgical technique in terms of post-operative complications, favorable outcomes, and rehabilitation.
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Safety and efficacy of iron therapy on reducing red blood cell transfusion requirements and treating anaemia in critically ill adults: A systematic review with meta-analysis and trial sequential analysis
Shah A, Fisher SA, Wong H, Roy NB, McKechnie S, Doree C, Litton E, Stanworth SJ
Journal of Critical Care. 2018;49:162-171.
Abstract
PURPOSE To evaluate the safety (risk of infection) and efficacy (transfusion requirements, changes in haemoglobin (Hb)) of iron therapy in adult intensive care unit (ICU) patients. MATERIALS AND METHODS We systematically searched seven databases for all relevant studies until January 2018 and included randomized (RCT) studies comparing iron, by any route, with placebo/no iron. RESULTS 805 participants from 6 RCTs were included. Iron therapy, by any route, did not decrease the risk of requirement for a red blood cell (RBC) transfusion (Risk ratio (RR) 0.91, 95% CI 0.80 to 1.04, p=0.15) or mean number of RBCs transfused per participant (mean difference (MD) -0.30, 95% CI -0.68 to 0.07, p=0.15). Iron therapy did increase mean Hb concentration (MD 0.31g/dL, 95% CI 0.04 to 0.59, p=0.03). There was no difference in infection (RR 0.95, 95% CI 0.79 to 1.19, p=0.44). Trial Sequential Analysis suggests that the required participant numbers to detect or reject a clinically important effect of iron therapy on transfusion requirements or infection in ICU patients has not yet been reached. CONCLUSION Iron therapy results in a modest increase in Hb. The current evidence is inadequate to exclude an important effect on transfusion requirements or infection.
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What is the effect of perioperative intravenous iron therapy in patients undergoing non-elective surgery? A systematic review with meta-analysis and trial sequential analysis
Shah A, Palmer AJR, Fisher SA, Rahman SM, Brunskill S, Doree C, Reid J, Sugavanam A, Stanworth SJ
Perioperative Medicine (London, England). 2018;7:30.
Abstract
Background: Guidelines to treat anaemia with intravenous (IV) iron have focused on elective surgical patients with little attention paid to those undergoing non-elective/emergency surgery. Whilst these patients may experience poor outcomes because of their presenting illness, observational data suggests that untreated anaemia may also be a contributing factor to poor outcomes. We conducted a systematic review to investigate the safety and efficacy of IV iron in patients undergoing non-elective surgery. Methods: We followed a pre-defined review protocol and included randomised controlled trials (RCTs) in patients undergoing non-elective surgery who received IV iron. Primary outcomes were all-cause infection and mean difference in haemoglobin (Hb) at follow-up. Secondary outcomes included transfusion requirements, hospital length of stay (LOS), health-related quality of life (HRQoL), mortality and adverse events. Results: Three RCTs (605 participants) were included in this systematic review of which two, in both hip fracture (HF) patients, provided data for meta-analysis. Both of these RCTs were at low risk of bias. We found no evidence of a difference in the risk of infection (RR 0.99, 95% CI 0.55 to 1.80, I (2) = 9%) or in the Hb concentration at 'short-term' (≤ 7 days) follow-up (mean difference - 0.32 g/L, 95% CI - 3.28 to 2.64, I (2) = 37%). IV iron did not reduce the risk of requiring a blood transfusion (RR 0.90, 95% CI 0.73 to 1.11, p = 0.46, I (2) = 0%), and we observed no difference in mortality, LOS or adverse events. One RCT reported on HRQoL and found no difference between treatment arms. Conclusion: We found no conclusive evidence of an effect of IV iron on clinically important outcomes in patients undergoing non-elective surgery. Further adequately powered trials to evaluate its benefit in emergency surgical specialties with a high burden of anaemia are warranted. Trial registration: This systematic review was registered on PROSPERO (CRD42018096288).
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Iron supplementation to treat anaemia in adult critical care patients: a systematic review and meta-analysis
Shah A, Roy NB, McKechnie S, Doree C, Fisher SA, Stanworth SJ
Critical Care (London, England). 2016;20((1)):306.
Abstract
BACKGROUND Anaemia affects 60-80 % of patients admitted to intensive care units (ICUs). Allogeneic red blood cell (RBC) transfusions remain the mainstay of treatment for anaemia but are associated with risks and are costly. Our objective was to assess the efficacy and safety of iron supplementation by any route, in anaemic patients in adult ICUs. METHODS Electronic databases (CENTRAL, MEDLINE, EMBASE) were searched through March 2016 for randomized controlled trials (RCT)s comparing iron by any route with placebo/no iron. Primary outcomes were red blood cell transfusions and mean haemoglobin concentration. Secondary outcomes included mortality, infection, ICU and hospital length of stay, mean difference (MD) in iron biomarkers, health-related quality of life and adverse events. RESULTS Five RCTs recruiting 665 patients met the inclusion criteria; intravenous iron was tested in four of the RCTs. There was no difference in allogeneic RBC transfusion requirements (relative risk 0.87, 95 % confidence interval (CI) 0.70 to 1.07, p = 0.18, five trials) or mean number of RBC units transfused (MD -0.45, 95 % CI -1.34 to 0.43, p = 0.32, two trials) in patients receiving or not receiving iron. Similarly, there was no difference between groups in haemoglobin at short-term (up to 10 days) (MD -0.25, 95 % CI -0.79 to 0.28, p = 0.35, three trials) or mid-term follow up (last measured time point in hospital or end of trial) (MD 0.21, 95 % CI -0.13 to 0.55, p = 0.23, three trials). There was no difference in secondary outcomes of mortality, in-hospital infection, or length of stay. Risk of bias was generally low although three trials had high risk of attrition bias; only one trial had low risk of bias across all domains. CONCLUSION Iron supplementation does not reduce RBC transfusion requirements in critically ill adults, but there is considerable heterogeneity between trials in study design, nature of interventions, and outcomes. Well-designed trials are needed to investigate the optimal iron dosing regimens and strategies to identify which patients are most likely to benefit from iron, together with patient-focused outcomes. TRIAL REGISTRATION PROSPERO International prospective register of systematic reviews CRD42015016627 . Registered 2 March 2015.
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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.