12 results found
Tan P-T, Cro S, Van Vogt E, et al., 2021, A review of the use of controlled multiple imputation in randomised controlled trials with missing outcome data, BMC Medical Research Methodology, Vol: 21, ISSN: 1471-2288
Background:Missing data are common in randomised controlled trials (RCTs) and can bias results if not handled appropriately. A statistically valid analysis under the primary missing-data assumptions should be conducted, followed by sensitivity analysis under alternative justified assumptions to assess the robustness of results. Controlled Multiple Imputation (MI) procedures, including delta-based and reference-based approaches, have been developed for analysis under missing-not-at-random assumptions. However, it is unclear how often these methods are used, how they are reported, and what their impact is on trial results. This review evaluates the current use and reporting of MI and controlled MI in RCTs.Methods:A targeted review of phase II-IV RCTs (non-cluster randomised) published in two leading general medical journals (The Lancet and New England Journal of Medicine) between January 2014 and December 2019 using MI. Data was extracted on imputation methods, analysis status, and reporting of results. Results of primary and sensitivity analyses for trials using controlled MI analyses were compared.Results:A total of 118 RCTs (9% of published RCTs) used some form of MI. MI under missing-at-random was used in 110 trials; this was for primary analysis in 43/118 (36%), and in sensitivity analysis for 70/118 (59%) (3 used in both). Sixteen studies performed controlled MI (1.3% of published RCTs), either with a delta-based (n = 9) or reference-based approach (n = 7). Controlled MI was mostly used in sensitivity analysis (n = 14/16). Two trials used controlled MI for primary analysis, including one reporting no sensitivity analysis whilst the other reported similar results without imputation. Of the 14 trials using controlled MI in sensitivity analysis, 12 yielded comparable results to the primary analysis whereas 2 demonstrated contradicting results. Only 5/110 (5%) trials using missing-at-random MI and 5/16 (31%) trials using con
Gohel M, Mora J, Szigeti M, et al., 2020, Long-term clinical and cost-effectiveness of early endovenous ablation in venous ulceration (The EVRA randomized clinical trial), JAMA: Journal of the American Medical Association, ISSN: 0098-7484
ImportanceOne-year outcomes from the Early Venous Reflux Ablation (EVRA) randomized trial showed accelerated venous leg ulcer healing and greater ulcer free time for participants treated with early endovenous ablation of lower extremity superficial reflux. Outcomes up to 5 years are presented here.ObjectiveTo evaluate the clinical and cost-effectiveness of early endovenous ablation of superficial venous reflux in patients with venous leg ulceration.DesignRandomized clinical trial.SettingVascular surgery departments in twenty United Kingdom hospitalsParticipantsBetween October 2013 and September 2016, 450 participants (450 legs) with venous leg ulceration of <6 months and superficial venous reflux were enrolled. InterventionsPatients were randomly assigned to receive compression therapy with early endovenous ablation within 2 weeks of randomization (early intervention, n=224) or compression with deferred endovenous treatment of superficial venous reflux (deferred intervention, n=226). Endovenous modality and strategy were left to the preference of the treating clinical team. Main outcomes and measuresThe primary outcome for the extended phase was time to first ulcer recurrence. Secondary outcomes included ulcer recurrence rate and cost effectiveness.ResultsOf 426 participants whose leg ulcer had healed, 121 (28.4%) experienced at least one recurrence during follow-up. There was no clear difference in time to first ulcer recurrence between the two groups (hazard ratio 0.82; 95% confidence interval [CI] 0.57 to 1.17; P=0.278). Ulcers recurred at a lower rate of 0.107 per person year (PY) in the early-intervention group compared to 0.162 per PY in the deferred-intervention group (incidence rate ratio 0.658; 95% CI: 0.480 to 0.898, p=0.003). Time to ulcer healing was shorter in the early-intervention group for primary ulcers (hazard ratio 1.36; 95% CI 1.12 to 1.64, p=0.002). At three years, early intervention is 91.6% likely to be cost-effective at a willingness to pa
Szigeti M, Ferenci T, Kovacs L, 2020, The use of block maxima method of extreme value statistics to characterise blood glucose curves, 2020 IEEE 15th International Conference of System of Systems Engineering (SoSE), Publisher: IEEE
Szigeti M, Ferenci T, Kovacs L, 2020, The use of peak over threshold methods to characterise blood glucose curves, 2020 IEEE 14th International Symposium on Applied Computational Intelligence and Informatics (SACI), Publisher: IEEE
Poulter NR, Savopoulos C, Anjum A, et al., 2018, Randomized crossover trial of the impact of morning or evening dosing of antihypertensive agents on 24-hour ambulatory blood pressure: the HARMONY trial, Hypertension, Vol: 72, Pages: 870-873, ISSN: 0194-911X
Some data suggest that nocturnal dosing of antihypertensive agents may reduce cardiovascular outcomes more than daytime dosing. This trial was designed to evaluate whether ambulatory blood pressure monitoring levels differ by timing of drug dosing. Patients aged 18 to 80 years with reasonably controlled hypertension (≤150/≤90 mm Hg) on stable therapy of ≥1 antihypertensive agent were recruited from 2 centers in London and Thessaloniki. Patients were randomized to receive usual therapy either in the morning (6 am–11 am) or evening (6 pm–11 pm) for 12 weeks when participants crossed over to the alternative timing for a further 12 weeks. Clinic blood pressures and a 24-hour recording were taken at baseline, 12, and 24 weeks and routine blood tests were taken at baseline. The study had 80% power to detect 3 mm Hg difference in mean 24-hour systolic blood pressure (α=0.05) by time of dosing. A 2-level hierarchical regression model adjusted for center, period, and sequence was used. Of 103 recruited patients (mean age, 62; 44% female), 95 patients (92%) completed all three 24-hour recordings. Mean 24-hour systolic and diastolic blood pressures did not differ between daytime and evening dosing. Similarly, morning and evening dosing had no differential impact on mean daytime (7 am–10 pm) and nighttime (10 pm–7 am) blood pressure levels nor on clinic levels. Stratification by age (≤65/≥65 years) or sex did not affect results. In summary, among hypertensive patients with reasonably well-controlled blood pressure, the timing of antihypertensive drug administration (morning or evening) did not affect mean 24-hour or clinic blood pressure levels.
Johnston SL, Szigeti M, Cross M, 2018, Correction: Azithromycin for acute exacerbations of Asthma: The AZALEA randomized clinical trial (JAMA Internal Medicine (2016) 176:11 (1630-1637) DOI: 10.1001/jamainternmed.2016.5664), JAMA Internal Medicine, Vol: 178, Pages: 1003-1003, ISSN: 2168-6106
© 2018 American Medical Association. All rights reserved. IncorrectNumbersofAdverseEventsReported: The Original Investigation titled "Azithromycin for Acute Exacerbations of Asthma: The AZALEAR and omized Clinical Trial,"1published in the November 2016 issue of JAMA Internal Medicine, reported incorrect numbers of adverse events owing to a recently discovered error in the AZALEA clinical trial database. In the last paragraph of the Results section, "a reduced frequency of respiratory, thoracic, and mediastinal (63 of 64 respiratory) adverse events (27 vs 37, respectively)" should read "a reduced frequency of respiratory, thoracic, and mediastinal (61 of 62 respiratory) adverse events (26 vs 36, respectively)." Inthe online-only Supplement, numbers of adverse events were reported incorrectly in eTables 16 through 19. This article and its supplement have been corrected online.
Johnston SL, Szigeti M, Cross M, et al., 2016, Azithromycin for acute exacerbations of asthma. The AZALEA randomized clinical trial, JAMA Internal Medicine, Vol: 176, Pages: 1630-1637, ISSN: 2168-6106
Importance Guidelines recommend against antibiotic use to treat asthma attacks. A study with telithromycin reported benefit, but adverse reactions limit its use.Objective To determine whether azithromycin added to standard care for asthma attacks in adults results in clinical benefit.Design, Setting, and Participants The Azithromycin Against Placebo in Exacerbations of Asthma (AZALEA) randomized, double-blind, placebo-controlled clinical trial, a United Kingdom–based multicenter study in adults requesting emergency care for acute asthma exacerbations, ran from September 2011 to April 2014. Adults with a history of asthma for more than 6 months were recruited within 48 hours of presentation to medical care with an acute deterioration in asthma control requiring a course of oral and/or systemic corticosteroids.Interventions Azithromycin 500 mg daily or matched placebo for 3 days.Main Outcomes and Measures The primary outcome was diary card symptom score 10 days after randomization, with a hypothesized treatment effect size of −0.3. Secondary outcomes were diary card symptom score, quality-of-life questionnaires, and lung function changes, all between exacerbation and day 10, and time to a 50% reduction in symptom score.Results Of 4582 patients screened at 31 centers, 199 of a planned 380 were randomized within 48 hours of presentation. The major reason for nonrecruitment was receipt of antibiotics (2044 [44.6%] screened patients). Median time from presentation to drug administration was 22 hours (interquartile range, 14-28 hours). Exacerbation characteristics were well balanced across treatment arms and centers. The primary outcome asthma symptom scores were mean (SD), 4.14 (1.38) at exacerbation and 2.09 (1.71) at 10 days for the azithromycin group and 4.18 (1.48) and 2.20 (1.51) for the placebo group, respectively. Using multilevel modeling, there was no significant difference in symptom scores between azithromycin and placebo at day 10 (difference
Poulter N, Anjum A, Cross M, et al., 2016, A comparison of the impact of morning or night delivery of antihypertensive agents on 24 hour ambulatory blood pressure monitoring (ABPM) levels: a randomised cross-over trial, Pages: 641-641
Poulter N, Anjum A, Cross M, et al., 2016, LBOS 01-01A COMPARISON OF THE IMPACT OF MORNING OR NIGHT DELIVERY OF ANTIHYPERTENSIVE AGENTS ON 24 HOUR ABPM LEVELS: A RANDOMISED CROSS-OVER TRIAL (HARMONY).
Poulter NR, Anjum A, Cross M, et al., 2016, [OP.LB01.07] A COMPARISON OF THE IMPACT OF MORNING OR NIGHT DELIVERY OF ANTIHYPERTENSIVE AGENTS ON 24 HOUR AMBULATORY BLOOD PRESSURE MONITORING (ABPM) LEVELS: A RANDOMISED CROSS-OVER TRIAL., Pages: e37-e38
Johnston SL, Szigeti M, Cross M, et al., 2016, A Randomised, Double-Blind, Placebo-Controlled Study To Evaluate The Efficacy Of Oral Azithromycin (500 Mg Od) As A Supplement To Standard Care For Adult Patients With Acute Exacerbations Of Asthma (the Azalea Trial), Publisher: AMER THORACIC SOC
Abbara A, Jayasena CN, Christopoulos G, et al., 2015, Efficacy of kisspeptin-54 to trigger oocyte maturation in women at high risk of OHSS during IVF therapy, Journal of Clinical Endocrinology and Metabolism, Vol: 100, Pages: 3322-3331, ISSN: 0368-1610
Context:In Vitro Fertilization (IVF) treatment is an effective therapy for infertility, but can result in the potentially life-threatening complication ‘ovarian hyperstimulation syndrome’ (OHSS).Objective:To investigate whether kisspeptin-54 can be used to effectively and safely trigger oocyte maturation in women undergoing IVF treatment at high risk of developing OHSS.Design:Phase 2 multi-dose open label randomized clinical trial carried out during 2013–2014.Setting:Hammersmith Hospital IVF unit, London, UK.Patients:Sixty women at high risk of developing OHSS Intervention:Following a standard recombinant FSH/GnRH antagonist protocol, patients were randomized to receive a single injection of kisspeptin-54 to trigger oocyte maturation using an adaptive design for dose allocation (3.2nmol/kg, n=5; 6.4nmol/kg, n=20; 9.6nmol/kg, n=15; 12.8nmol/kg, n=20). Oocytes were retrieved 36hrs after kisspeptin-54 administration, assessed for maturation, and fertilized by intra-cytoplasmic sperm injection (ICSI) with subsequent transfer of one or two embryos. Women were routinely screened for the development of OHSS.Main Outcome Measure:Oocyte maturation was measured by oocyte yield (percentage of mature oocytes retrieved from follicles ≥14mm on ultrasound). Secondary outcomes include rates of OHSS and pregancy. Results:Oocyte maturation occurred in 95% of women. Highest oocyte yield (121%) was observed following 12.8nmol/kg kisspeptin-54, which was +69% (CI -16%,+153%) greater than following 3.2nmol/kg. At all doses of kisspeptin-54, biochemical pregnancy, clinical pregnancy and live birth rates per transfer (n=51) were 63%, 53% and 45%, respectively. Highest pregnancy rates were observed following 9.6nmol/kg kisspeptin-54 (85%, 77% and 62%, respectively). No woman developed moderate, severe or critical OHSS.Conclusion:Kisspeptin-54 is a promising approach to effectively and safely trigger oocyte
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