reduced dose
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Trials ◽  
2022 ◽  
Vol 23 (1) ◽  
Author(s):  
Grant A. Mackenzie ◽  
Isaac Osei ◽  
Rasheed Salaudeen ◽  
Ousman Secka ◽  
Umberto D’Alessandro ◽  
...  

Abstract Background Pneumococcal conjugate vaccines (PCVs) effectively prevent pneumococcal disease, but the global impact of pneumococcal vaccination is hampered by its cost. The evaluation of reduced dose schedules of PCV includes measurement of effects on immunogenicity and carriage acquisition compared to standard schedules. The relevance and feasibility of trials of reduced dose schedules is greatest in middle- and low-income countries, such as The Gambia, where the introduction of PCV resulted in good disease control but where transmission of vaccine-type pneumococci persists. We designed a large cluster-randomised field trial of an alternative reduced dose schedule of PCV compared to the standard schedule, the PVS trial. We will also conduct a sub-study to evaluate the individual-level effect of the two schedules on carriage acquisition, immunogenicity, and co-administration of PCV with yellow fever vaccine, the PVS-AcqImm trial. Methods PVS-AcqImm is a prospective, cluster-randomised trial of one dose of PCV scheduled at age 6 weeks with a booster dose at age 9 months (i.e. alternative ‘1+1’ schedule) compared to three primary doses scheduled at 6, 10, and 14 weeks of age (i.e. standard ‘3+0’ schedule). Sub-groups within the alternative schedule group will receive yellow fever vaccine separately or co-administered with PCV at 9 months of age. The primary endpoints are (a) rate of nasopharyngeal vaccine-type pneumococcal acquisition from 9 to 14 months of age, (b) geometric mean concentration of vaccine-type pneumococcal IgG at 18 months of age, and (c) proportions with yellow fever neutralising antibody titre ≥8 four weeks after administration of yellow fever vaccine. Participants and field staff will not be masked to group allocation while the measurement of laboratory endpoints will be masked. Approximately equal numbers of participants will be resident in each of 28 geographic clusters (14 clusters in alternative and standard schedule groups); 784 enrolled for acquisition measurements and 336 for immunogenicity measurements. Discussion Analysis will account for potential non-independence of measurements by cluster and so interpretation of effects will be at the individual level (i.e. a population of individuals). PVS-AcqImm will evaluate whether acquisition of vaccine-type pneumococci is reduced by the alternative compared to the standard schedule, which is required if the alternative schedule is to be effective. Likewise, evidence of superior immune response at 18 months of age and safety of PCV co-administration with yellow fever vaccine will support decision-making regarding the use of the alternative 1+1 schedule. Acquisition and immunogenicity outcomes will be essential for the interpretation of the results of the large field trial comparing the two schedules. Trial registration International Standard Randomised Controlled Trial Number 72821613.


Radiology ◽  
2022 ◽  
Author(s):  
Corey T. Jensen ◽  
Shiva Gupta ◽  
Mohammed M. Saleh ◽  
Xinming Liu ◽  
Vincenzo K. Wong ◽  
...  

2021 ◽  
Vol 50 (1) ◽  
pp. 374-374
Author(s):  
Catherine To ◽  
Teresa Allison ◽  
Sarah Brinson

2021 ◽  
Author(s):  
Grant Austin Mackenzie ◽  
Isaac Osei ◽  
Rasheed Salaudeen ◽  
Ilias Hossain ◽  
Benjamin Young ◽  
...  

Abstract Background:Pneumococcal conjugate vaccines (PCV) effectively prevent pneumococcal disease but the global impact of pneumococcal vaccination is hampered by the cost of PCV. The relevance and feasibility of trials of reduced dose schedules is greatest in middle- and low-income countries, such as The Gambia, where PCV has been introduced with good disease control but where transmission of vaccine-type pneumococci persists. We are conducting a large cluster-randomised, non-inferiority, field trial of an alternative reduced dose schedule of PCV compared to the standard schedule, the PVS trial.Methods:PVS is prospective, cluster-randomised, non-inferiority, real-world field trial of an alternative schedule of one dose of PCV scheduled at age 6 weeks with a booster dose at age 9 months (i.e. the alternative ‘1+1’ schedule) compared to the standard schedule of three primary doses scheduled at 6, 10, and 14 weeks weeks of age (i.e. the stardard ‘3+0’ schedule). The intervention will be delivered for 4 years. The primary endpoint is the population-level prevalence of nasopharyngeal vaccine-type pneumococcal carriage in children aged 2 weeks to 59 months with clinical pneumonia in Year 4 of the trial. Participants and field staff are not masked to group allocation while measurement of the laboratory endpoint will be masked. Sixty-eight geographic population clusters have been randomly allocated, in a 1:1 ratio, to each schedule and all resident infants are eligible for enrolment. All resident children less than 5 years of age are under continuous surveillance for clinical safety endpoints measured at 11 health facilities; invasive pneumococcal disease, radiological pneumonia, clinical pneumonia, and hospitalisations. Secondary endpoints include the population-level prevalence of nasopharyngeal vaccine-type pneumococcal carriage in Year 2 and 4 and vaccine-type carriage prevalence in unimmunised infants aged 6-12 weeks in Year 4. The trial includes components of mathematical modeling, health economics, and health systems research.Discussion:Analysis will account for potential non-independence of measurements by cluster, comparing the population-level impact of the two schedules with interpretation at the individual level. The non-inferiority margin is informed by the ‘acceptable loss of effect’ of the alternative compared to standard schedule. The secondary endpoints will provide substantial evidence to support the interpretation of the primary endpoint. PVS will evaluate the effect of transition from a standard 3+0 schedule to an alternative 1+1 schedule in a setting of high pneumococcal transmission. The results of PVS will inform global decision-making concerning the use of reduced-dose PCV schedules.Trial registration: International Standard Randomised Controlled Trial Number – 15056916.


Author(s):  
Anna Cederborg ◽  
Åsa Norén ◽  
Thijs Barten ◽  
Björn Lindkvist ◽  
William Bennet ◽  
...  

BMJ Open ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. e056487
Author(s):  
Ewoud ter Avest ◽  
Dassen Ragavan ◽  
Joanne Griggs ◽  
Michael Dias ◽  
Sophie A Mitchinson ◽  
...  

ObjectivesPrehospital rapid sequence induction (RSI) of anaesthesia is an intervention with significant associated risk. In this study, we aimed to investigate the haemodynamic response over time of a prehospital RSI protocol of fentanyl, ketamine and rocuronium in a heterogeneous population of trauma patients.Design, setting and participantWe performed a retrospective study of all trauma patients who received a prehospital RSI for trauma by a physician staffed Helicopter Emergency Medical Service in the UK between 1 June 2018 and 1 February 2020.Primary outcome measurePrimary outcome was defined as the incidence of clinically relevant hypotensive (systolic blood pressure (SBP) or mean arterial pressure (MAP) >20% below baseline, with an absolute SBP <90 mm Hg or MAP <65 mm Hg) or hypertensive (SBP or MAP >20% above baseline) episodes in the first 10 minutes post-RSI.ResultsIn total, 322 patients were included. 204 patients (63%) received a full-dose induction of 3 μg/kg fentanyl, 2 mg/kg ketamine and 1 mg/kg rocuronium, whereas 128 patients (37%) received a reduced-dose induction. Blood pressures decreased on average 12 mm Hg (95% CI 7 to 16) in the full-dose group and 6 mm Hg (95% CI 1 to 11) in the reduced-dose group, p=0.10). A hypotensive episode (mean SBP drop 53 mm Hg) was noted in 29 patients: 17 (8.3%) receiving a full dose and 12 (10.2%) receiving a reduced-dose induction, p=0.69. The blood pressure nadir was recorded on average 6–8 min after RSI. A hypertensive episode was present in 22 patients (6.8%). The highest blood pressures were recorded in the first 3 min after RSI.ConclusionPrehospital induction of anaesthesia for trauma with fentanyl, ketamine and rocuronium is not related to a significant change in haemodynamics in most patients. However, a (delayed) hypotensive response with a significant drop in SBP should be anticipated in a minority of patients irrespective of the dose regimen chosen.


2021 ◽  
Author(s):  
Niyati Lobo ◽  
Kelly K. Bree ◽  
Patrick J. Hensley ◽  
Graciela M. Nogueras‐Gonzalez ◽  
Prasanth Abraham ◽  
...  

2021 ◽  
Vol 12 ◽  
Author(s):  
Ziyu Wang ◽  
Xin Du ◽  
Ken Chen ◽  
Shanshan Li ◽  
Zhiheng Yu ◽  
...  

Background and Aim: As one of the second-generation epidermal growth factor receptor (EGFR)–tyrosine kinase inhibitors, afatinib brings survival benefits to patients with common and rare EGFR mutations. This study aimed to compare the effectiveness and safety of 30 and 40 mg of afatinib in patients with non–small cell lung cancer (NSCLC) using qualitative and quantitative analysis methods so as to provide reference for clinical medication.Methods: The PubMed, Embase, ClinicalTrials.gov, Cochrane Library, China National Knowledge Infrastructure, and WanFang databases were thoroughly searched from inception to February 26, 2021. Two researchers independently screened the literature, extracted data, and evaluated the quality. RevMan and Stata 15.0 were used for meta-analysis.Results: Twelve cohort studies including 1290 patients for final analysis were selected; of which, 1129 patients were analyzed to measure the effectiveness outcomes and 470 patients were analyzed for safety outcomes. In patients with non-brain metastasis, the progression-free survival of the first- or second-line treatment with reduced-dose afatinib was equivalent to the conventional dose. In terms of safety, the reduced dose could significantly lower the incidence of severe diarrhea and severe rash, but not the total incidence of diarrhea, rash, and all levels of paronychia.Conclusions: The incidence of common serious adverse reactions was significantly lower with 30 mg of afatinib than with 40 mg of afatinib in patients with NSCLC. The effectiveness appeared to be similar to that in patients with non-brain metastasis. This study provides a reference for clinical dose reduction of afatinib.Systematic Review Registration: [PROSPERO], identifier [CRD42021238043]


Author(s):  
Louisa Stone ◽  
Eileen Merriman ◽  
Gordon Royle ◽  
Merit Hanna ◽  
Henry Chan

Background The recommended dose of idarucizumab, the specific reversal agent for dabigatran etexilate, is 5g. However, published data showed biochemical reversal after an initial 2.5g dose. Objectives This study aims to retrospectively compare the clinical effectiveness of 2.5g and 5g doses of idarucizumab used in dabigatran reversal in three hospitals in Auckland, New Zealand. Methods All patients receiving idarucizumab for dabigatran reversal between 1st April 2016 and 31st December 2018 were included. The primary outcome was the likelihood of receiving a second dose of idarucizumab during the same admission. Secondary outcomes included normalisation of coagulation profiles; and 30-day thrombotic, bleeding and mortality rates. Results Of 329 patients included, 206 received an upfront 2.5g dose and 123 received a 5g dose. The median age was 78 years and median creatinine clearance was 50mL/min. Most patients (62.6%) required idarucizumab for an urgent procedure, while 37.4% presented with bleeding. A 2.5g dose was not associated with an increased rate of receiving a second dose (OR 0.686, 95% CI 0.225-2.090). A similar proportion of patients in each group achieved a normal APTT (73.8% vs 80.0%, p=0.464) and dTCT (95.9% vs 91.4%, p=0.379) following idarucizumab infusion. There was no increase in the rate of death (OR 0.602, 95% CI 0.292-1.239), thrombosis (OR 0.386, 95% CI 0.107-1.396) or bleeding (OR 0.96, 95% CI 0.27-3.33) in the 2.5g dose group compared to the 5g dose group. Conclusions An initial 2.5g dose of idarucizumab appears effective for dabigatran reversal in the real-world setting.


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