Publications
25 results found
Maher TM, Tudor VA, Saunders P, et al., 2024, Rituximab compared to intravenous cyclophosphamide in adults with connective tissue disease-associated interstitial lung disease: the RECITAL RCT, Efficacy and Mechanism Evaluation, Pages: 1-68, ISSN: 2050-4365
<jats:sec id="abs1-1"><jats:title>Background</jats:title><jats:p>Interstitial lung disease frequently complicates systemic autoimmune disorders including scleroderma, idiopathic inflammatory myositis and mixed connective tissue disease, resulting in considerable morbidity and mortality. Based on the results of trials undertaken in scleroderma, cyclophosphamide is the standard of care for individuals with severe or progressive connective tissue disease-associated interstitial lung disease. Observational studies suggest that the anti-CD20 monoclonal antibody, rituximab is an effective rescue therapy in treatment of refractory connective tissue disease-associated interstitial lung disease, but it has not been studied as first-line therapy in clinical trials.</jats:p></jats:sec><jats:sec id="abs1-2"><jats:title>Objectives</jats:title><jats:p>To compare the safety and efficacy of rituximab against that of cyclophosphamide as treatment for individuals with severe, progressive interstitial lung disease associated with scleroderma, idiopathic inflammatory myositis or mixed connective tissue disease.</jats:p></jats:sec><jats:sec id="abs1-3"><jats:title>Methods</jats:title><jats:p>This was a Phase IIb, multicentre, randomised, double-blind, double-dummy study assessing the superiority of rituximab compared with cyclophosphamide, conducted in rheumatology or interstitial lung disease units at 11 UK centres. The study recruited individuals with extensive and/or progressive connective tissue disease-associated interstitial lung disease, excluding those with significant comorbidities, including airflow obstruction. Participants were randomised 1 : 1 to receive either rituximab 1 g given intravenously, twice at an interval of 2 weeks, or intravenous cyclophosphamide given monthly for 6 months at a dose of 600 mg/m<jats:sup>2</jats:sup> body surf
Nagy Z, Kiss N, Szigeti M, et al., 2024, Construct validity of the Hungarian Version of the Patient-Reported Outcomes Measurement Information System-29 Profile Among Patients with Low Back Pain., World Neurosurg, Vol: 181, Pages: e55-e66
OBJECTIVE: We aim to evaluate the psychometric properties of the Hungarian version of the patient-reported outcomes measurement information system (PROMIS)-29 profile domains among patients with chronic low back pain. METHODS: We used a convenience, cross-sectional sampling of patients recruited at our neurosurgical institution. The participants completed paper-pencil version of the PROMIS-29 profile in addition to validated legacy questionnaires, including the Oswestry disability index, Research and Development Corporation 36-item short-form survey, 7-item general anxiety disorder scale, 9-item patient health questionnaire. Reliability was evaluated by calculating the internal consistency (Cronbach's α). Test-retest reliability was assessed using the intraclass correlation coefficient. The structural validity of PROMIS-29 was assessed using a confirmatory factor analysis. Construct validity was assessed by evaluating convergent and discriminant validity using Spearman's rank correlation. To further corroborate the construct validity, we also performed known-group comparisons. RESULTS: The mean age of the 131 participants was 54 ± 16 years. Of the 131 patients, 62% were women. The internal consistency of each PROMIS domain was high (Cronbach's α >0.89 for all). The test-retest reliability was excellent (intraclass correlation >0.97). The confirmatory factor analysis showed good structural validity (comparative fit index >0.96; standardized root mean square residual <0.026 for all domains). All measured PROMIS scores correlated strongly with the scores obtained using the corresponding primary legacy instrument, indicating excellent convergent validity. The known-group comparisons demonstrated differences as hypothesized. CONCLUSIONS: We present data supporting the validity and reliability of the Hungarian PROMIS-29 profile short forms for patients with low back pain. This instrument will be useful for research and clinical applications
Merkely B, Hatala R, Wranicz JK, et al., 2023, Upgrade of right ventricular pacing to cardiac resynchronization therapy in heart failure: a randomized trial., Eur Heart J, Vol: 44, Pages: 4259-4269
BACKGROUND AND AIMS: De novo implanted cardiac resynchronization therapy with defibrillator (CRT-D) reduces the risk of morbidity and mortality in patients with left bundle branch block, heart failure and reduced ejection fraction (HFrEF). However, among HFrEF patients with right ventricular pacing (RVP), the efficacy of CRT-D upgrade is uncertain. METHODS: In this multicentre, randomized, controlled trial, 360 symptomatic (New York Heart Association Classes II-IVa) HFrEF patients with a pacemaker or implantable cardioverter defibrillator (ICD), high RVP burden ≥ 20%, and a wide paced QRS complex duration ≥ 150 ms were randomly assigned to receive CRT-D upgrade (n = 215) or ICD (n = 145) in a 3:2 ratio. The primary outcome was the composite of all-cause mortality, heart failure hospitalization, or <15% reduction of left ventricular end-systolic volume assessed at 12 months. Secondary outcomes included all-cause mortality or heart failure hospitalization. RESULTS: Over a median follow-up of 12.4 months, the primary outcome occurred in 58/179 (32.4%) in the CRT-D arm vs. 101/128 (78.9%) in the ICD arm (odds ratio 0.11; 95% confidence interval 0.06-0.19; P < .001). All-cause mortality or heart failure hospitalization occurred in 22/215 (10%) in the CRT-D arm vs. 46/145 (32%) in the ICD arm (hazard ratio 0.27; 95% confidence interval 0.16-0.47; P < .001). The incidence of procedure- or device-related complications was similar between the two arms [CRT-D group 25/211 (12.3%) vs. ICD group 11/142 (7.8%)]. CONCLUSIONS: In pacemaker or ICD patients with significant RVP burden and reduced ejection fraction, upgrade to CRT-D compared with ICD therapy reduced the combined risk of all-cause mortality, heart failure hospitalization, or absence of reverse remodelling.
Kanagaratnam P, Francis DP, Chamie D, et al., 2023, A randomised controlled trial to investigate the use of acute coronary syndrome therapy in patients hospitalised with COVID-19: the C19-ACS trial, Journal of Thrombosis and Haemostasis, Vol: 21, Pages: 2213-2222, ISSN: 1538-7836
BACKGROUND: Patients hospitalised with COVID-19 suffer thrombotic complications. Risk factors for poor outcomes are shared with coronary artery disease. OBJECTIVES: To investigate efficacy of an acute coronary syndrome regimen in patients hospitalised with COVID-19 and coronary disease risk factors. PATIENTS/METHODS: A randomised controlled open-label trial across acute hospitals (UK and Brazil) added aspirin, clopidogrel, low-dose rivaroxaban, atorvastatin, and omeprazole to standard care for 28-days. Primary efficacy and safety outcomes were 30-day mortality and bleeding. The key secondary outcome was a daily clinical status (at home, in hospital, on intensive therapy unit admission, death). RESULTS: 320 patients from 9 centres were randomised. The trial terminated early due to low recruitment. At 30 days there was no significant difference in mortality (intervention: 11.5% vs control: 15%, unadjusted OR 0.73, 95%CI 0.38 to 1.41, p=0.355). Significant bleeds were infrequent and not significantly different between the arms (intervention: 1.9% vs control 1.9%, p>0.999). Using a Bayesian Markov longitudinal ordinal model, it was 93% probable that intervention arm participants were more likely to transition to a better clinical state each day (OR 1.46, 95% CrI 0.88 to 2.37, Pr(Beta>0)=93%; adjusted OR 1.50, 95% CrI 0.91 to 2.45, Pr(Beta>0)=95%) and median time to discharge home was two days shorter (95% CrI -4 to 0, 2% probability that it was worse). CONCLUSIONS: Acute coronary syndrome treatment regimen was associated with a reduction in the length of hospital stay without an excess in major bleeding. A larger trial is needed to evaluate mortality.
Zadori A, Kis Z, Toth T, et al., 2023, Long-Term Efficacy and Safety of Left Atrial Appendage Closure Procedures., Int Heart J, Vol: 64, Pages: 188-195
The aim of the present single-center, nonrandomized, retrospective study was to assess the safety and long-term efficacy of percutaneous left atrial appendage closure (LAAC) procedures and to compare the different LAAC devices and therapeutic regimes in this respect.Medical data of 136 patients (pts) (mean age, 72.5 ± 7.6 years; score for atrial fibrillation stroke risk estimation [CHA2DS2-VASc], 4.6 ± 1.6; and score for estimation of major bleeding risk for patients on anticoagulant therapy [HAS-BLED], 2.6 ± 0.9) who underwent percutaneous LAAC procedures in Gottsegen National Cardiovascular Center from January 2010 to January 2020 were analyzed.The rates of outpatient cardiac mortality, ischemic brain event, and major bleeding were 3.8, 1, and 1.9/100 pt years, respectively. The rate of successful device deployment was 96.4%. There was one case of procedural mortality (0.7%), one case of device dislocation (0.7%), one case of ischemic stroke (0.7%), and one case of myocardial infarction (0.7%). Two cases of pericardial tamponades (1.5%) and four cases of major femoral complications (3%) occurred. Although the implantation success of different occluder types was similar, significant differences were found concerning procedural characteristics. Patients on single antiplatelet therapy (SAPT) in the first 3 months after the LAAC procedure did not suffer from stroke or embolic events.The present study confirmed the safety and effectivity of percutaneous LAAC. Robust relative stroke risk reduction and less pronounced but significant bleeding risk reduction were observed. Device implantation success was high. The perioperative complication rate was relatively low. The results of long-term observations regarding ischemic events confirmed the safety of using a simplified antithrombotic regime after LAAC in pts with high bleeding risk.
Szigeti M, Ferenci T, Kovacs L, 2023, The Use of Extreme Value Statistics to Characterize Blood Glucose Curves and Patient Level Risk Assessment of Patients With Type I Diabetes, JOURNAL OF DIABETES SCIENCE AND TECHNOLOGY, Vol: 17, Pages: 400-408, ISSN: 1932-2968
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Maher TM, Tudor VA, Saunders P, et al., 2023, Rituximab versus intravenous cyclophosphamide in patients with connective tissue disease-associated interstitial lung disease in the UK (RECITAL): a double-blind, double-dummy, randomised, controlled, phase 2b trial, The Lancet Respiratory Medicine, Vol: 11, Pages: 45-54, ISSN: 2213-2600
BACKGROUND: Rituximab is often used as rescue therapy in interstitial lung disease (ILD) associated with connective tissue disease (CTD), but has not been studied in clinical trials. This study aimed to assess whether rituximab is superior to cyclophosphamide as a treatment for severe or progressive CTD associated ILD. METHODS: We conducted a randomised, double-blind, double-dummy, phase 2b trial to assess the superiority of rituximab compared with cyclophosphamide. Patients aged 18-80 years with severe or progressive ILD related to scleroderma, idiopathic inflammatory myositis, or mixed CTD, recruited across 11 specialist ILD or rheumatology centres in the UK, were randomly assigned (1:1) to receive rituximab (1000 mg at weeks 0 and 2 intravenously) or cyclophosphamide (600 mg/m2 body surface area every 4 weeks intravenously for six doses). The primary endpoint was rate of change in forced vital capacity (FVC) at 24 weeks compared with baseline, analysed using a mixed-effects model with random intercepts, adjusted for baseline FVC and CTD type. Prespecified secondary endpoints reported in this Article were change in FVC at 48 weeks versus baseline; changes from baseline in 6 min walk distance, diffusing capacity of the lung for carbon monoxide (DLCO), physician-assessed global disease activity (GDA) score, and quality-of-life scores on the St George's Respiratory Questionnaire (SGRQ), King's Brief Interstitial Lung Disease (KBILD) questionnaire, and European Quality of Life Five-Dimension (EQ-5D) questionnaire at 24 and 48 weeks; overall survival, progression-free survival, and time to treatment failure; and corticosteroid use. All endpoints were analysed in the modified intention-to-treat population, which comprised all patients who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov (NCT01862926). FINDINGS: Between Dec 1, 2014, and March 31, 2020, we screened 145 participants, of whom 101 participants were randomly allocated
Maher T, Tudor V, Saunders P, et al., 2022, Rituximab versus Cyclophosphamide for the Treatment of Connective Tissue Disease Associated Interstitial Lung Disease (RECITAL): A Sub-group Analysis of a Multi-centre Randomised Controlled Trial, Publisher: WILEY, Pages: 5-7, ISSN: 2326-5191
Vadon NB, Elek LP, Szigeti M, et al., 2022, Association between Lifestyle- and Circadian Rhythm-Related Changes, and Different Depression Symptom Clusters during COVID-19., Psychiatr Danub, Vol: 34, Pages: 81-89, ISSN: 0353-5053
BACKGROUND: The COVID-19 pandemic brought along a new situation for the population worldwide. The most important safety measures and lockdown expected extreme adaptability and flexibility impacting mental well-being. The aim of our study was to identify associations between changes in lifestyle and circadian rhythm and depression during the pandemic. SUBJECTS AND METHODS: Our analysis has been carried out on the Hungarian data set of the COMET-G study including information on lifestyle and circadian rhythm-associated factors and severity of depression and its 3 symptom clusters. Associations were assessed using linear regression models adjusted for age and sex. RESULTS: All variables reflecting changes in quality and quantity of sleep showed significant associations with overall depression scores and the three distinct symptom cluster scores. All variables reflecting importance and changes in physical activity during the pandemic were similarly significantly associated with all depression measures. However, only changes in quality of diet, but not quantity was associated with depression scores. CONCLUSIONS: Our results may confirm the association of circadian rhythm and lifestyle-related environmental factors in deterioration of mental health during COVID and help devise prevention and intervention methods and targets for similar situations.
Elek LP, Szigeti M, Erdelyi-Hamza B, et al., 2022, What you see is what you get? Association of belief in conspiracy theories and mental health during COVID-19., Neuropsychopharmacol Hung, Vol: 24, Pages: 42-55, ISSN: 1419-8711
Background: The COVID-19 pandemic brought about great uncertainty and significant changes in our people's everyday lives. In times of such crises, it is natural to seek explanations to overcome our fears and uncertainties, contributing to an increase to believe in conspiracy theories which, by yielding explanations, decrease uncertainty and ambiguity and may thus have an effect on mental well-being. In spite of this, the majority of research on conspiracy theories focused on their social effects with little attention to psychological effects. Thus, the aim of our present study was to examine the association between belief in conspiracy theories and different aspects of mental health during the COVID-19 pandemic in a general population sample. Methods: Our analyses included data from the Hungarian leg of the COMET-G (COVID-19 MEntal health international for the General population) study. The Hungarian sample included participants who completed a detailed questionnaire assessing belief in seven conspiracy theory items, as well as STAI-S and CES-D to measure state anxiety and depression, respectively, and answered questions related to their change in depression, anxiety and suicidal thoughts during the pandemic. Association between the individual beliefs as well as a composite Conspiracy Theory Belief Score (CTBS) and mental health measures was analysed using linear regression models. Results: Overall, belief in conspiracy theories was relatively moderate in our sample. Sex and age appeared to have a significant effect on the Overall Conspiracy Theory Belief Score (CTBS), with women having a higher score and scores increasing with age. Some of the individual beliefs also showed associations with age and sex. State anxiety and depression was not significantly associated with CTBS, however in case of depression some individual items were, and symptom clusters within CES-D also showed a pattern of association with some of the individual items. As far as changes in mental
Ferenci T, Szigeti M, Kovacs L, 2022, Using non-stationary extreme value analysis to characterize blood glucose curves, Pages: 171-176
Introduction: The application of extreme value statistics provides a novel way to characterize the risk of high blood glucose levels. Its statistical methodology works well for dependent data, but the impact of non-stationarity is unclear.Material and Methods: 14.7 million blood glucose measurements from 225 patients were analyzed with stationary and nonstationary extreme value models. In case of the latter, the location parameter was allowed to vary with time using spline expansion to allow for a flexible, data-driven functional form.Results: Estimated scale and shape parameters were almost identical (correlation > 0.99) and estimated location was also similar (correlation =0.9). One-year return level and estimated time spent in a year above the clinically relevant threshold of 600 mg/dl was also very similar, and estimated time spent above 400 mg/dl was similar with the exception of a single patient, who had much higher value with the stationary model.Discussion and Conclusion: Non-stationary extreme values models can be applied to analyze blood glucose measurements with the aim of measuring the risk of hyperglycaemia. Obtained results are similar to those with stationary models, but whether it is possible (and if so, to what extent) that the estimated longterm trend in location picks up some effect of true extremity requires further investigation.
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, Pages: 433-437
In contrast to regular statistics where the focus is on the most typical part of the data and the used metrics are describing that part (usually with the mean or median and variance and interquartile range) where most of the observations came from, there is a branch of statistics which focuses on the extreme events, i.e, the tails of the distributions. These are not simple outliers, like data entry errors, but real part of the data which are far from the central tendency and occur rarely, yet, have relevance and impact. Thus, in many application, they can't be simply neglected. The use of extreme value statistics allows us to fit models on this part of the data and like 'regular' statistics, enables us to calculate estimates and predictions, but in this case for extreme values. These methods are frequently used in fields like meteorology and finance where the extreme events have large impact despite their rarity. Because of this rarity, however, only a small fraction of the data can be used so much higher sample size is required for such analysis. This factor limited the use of extreme value statistics in biomedical field where available technology and costs are strong limitations at frequently measuring most of the biomarkers until recently. Blood glucose level is one of the exceptions nowadays, as with recent advancements it can be monitored for relatively long time and with high frequency for a patient. Additionally, extreme values of blood glucose levels (both high and low) are associated with- chronic or acute- complications of diabetes. This paper aims to demonstrate that the use of extreme value statistics, in particular the block maxima approach could be a possible way to characterize blood glucose curves. In addition to providing a metric for the state of the patient and therefore hopefully the associated risks, it allows the comparison of the performance of artificial pancreas systems. Block maxima method was used to model extreme values of a dataset conta
Szigeti M, Ferenci T, Kovacs L, 2020, The use of peak over threshold methods to characterise blood glucose curves, Pages: 199-204
In contrast to regular statistics which focuses on the typical part of the data and use metrics to describe that part (usually the mean or variance), there is a branch of statistics which focuses on the extreme and thus rare events. The use of extreme value statistics allows us to fit models on this part of the data and like regular statistics, enables us to calculate estimates and predictions, but in this case for extreme values. These methods are frequently used in fields like meteorology and finance where the extreme events has large impact despite their rarity. Because of this rarity, however, only a small fraction of the data can be used so much higher sample size is required for such analysis - thus fields with a large amount of historical data have an advantage.This factor limited the use of extreme value statistics in biomedical field where available technology and costs are strong limitations at measuring most of the biomarkers until recently.Blood glucose level is one of the exceptions nowadays, as with recent advancements it can be monitored for relatively long time and with high frequency for a patient. Additionally, extreme values of blood glucose levels (both high and low) are associated with - chronic or acute - complications of diabetes.This paper aims to demonstrate that the use of extreme value statistics could be a possible way to characterize blood glucose curves. In addition to providing a metric for the state of the patient, it allows the comparison of the performance of artificial pancreas models.Peak over threshold method was used to model extreme values of a simulated dataset containing 1440 measurements of 99 patients with 250 mg/dl as threshold. Probabilities for exceeding the clinically relevant levels of 270 mg/dl (cognitive symptoms expected) and 600 mg/dl (diabetic hyperosmolar syndrome) were calculated and were 23.9% and 8.0 • 10-6% respectively in the region above the threshold (250 mg/dl). Through these estimates it is possible
Szigeti M, Kovács L, Ferenci T, 2019, Stability of relative and absolute metrics: Empirical evidence from pulmonology, Pages: 235-238
It has been widely argued that absolute treatment effect measurements (such as risk difference) reveal the "clinical benefit" of an intervention. Yet, many previous experience with binary endpoints have shown that they are unlikely to be transportable between populations. As absolute metrics are usually derived from baseline risk and relative metric (such as odds ratio), it seems logical to rather measure relative metrics, assuming they are stable. In the present study, a continuous endpoint was used to assess the stability of both relative and absolute metrics using a empirical data from pulmonology. Results are preliminary due to the low baseline variability, yet, the difference was significantly correlated with the baseline, unlike the ratio, which is in line with previous experience with binary endpoints. Further research is needed to explore the stability with continuous endpoints.
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.
Tsipouri V, Saunders P, Keir GJ, et al., 2017, Rituximab versus cyclophosphamide for the treatment of connective tissue disease associated interstitial lung disease (RECITAL): a randomised controlled trial, Publisher: BIOMED CENTRAL LTD, ISSN: 1745-6215
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 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
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 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
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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