Publications
229 results found
Kassavou A, Mirzaei V, Shpendi S, et al., 2021, The feasibility of the PAM intervention to support treatment-adherence in people with hypertension in primary care: a randomised clinical controlled trial, SCIENTIFIC REPORTS, Vol: 11, ISSN: 2045-2322
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- Citations: 1
Naughton F, Brown C, High J, et al., 2021, Randomised controlled trial of a just-in-time adaptive intervention (JITAI) smoking cessation smartphone app: the Quit Sense feasibility trial protocol, BMJ OPEN, Vol: 11, ISSN: 2044-6055
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- Citations: 3
Eldred-Evans D, Burak P, Connor M, et al., 2021, Population-based prostate cancer screening with Magnetic Resonance Imaging or Ultrasonography: the IP1-PROSTAGRAM study, JAMA Oncology, Vol: 7, Pages: 395-402, ISSN: 2374-2445
Importance: Screening for prostate cancer using PSA-testing can lead to problems of under- and over-diagnosis. A short, non-contrast MRI or transrectal ultrasound might overcome these limitations. Objective: To compare the performance of PSA, MRI and ultrasound as screening tests for prostate cancer. Design, Setting and Participants: This prospective, population-based, blinded cohort study was conducted at seven primary care practices and two imaging centres in the UK. 2034 community based men aged 50-69 years invited for prostate cancer screening and 408 were consented. Interventions: All participants underwent screening with a PSA test, MRI (T2-weighted and diffusion) and ultrasound (b-mode and shearwave elastography).-The tests were independently interpreted without knowledge of other results. Both imaging tests were reported on a validated 5-point scale of suspicion. If any test was screen-positive, a systematic 12-core biopsy was performed. Additionalimage-fusion targeted biopsies were taken if the MRI or ultrasound was positive. Main Outcomes and Measures: The proportion of men with screen-positive MRI or ultrasound (defined as either score 3-5 or 4-5) or screen-positive PSA (defined as PSA≥3g/L). Key secondary outcomes were the number of clinically-significant and clinically-insignificant cancers detected if each test was used exclusively. Clinically-significant cancer was defined as any Gleason score≥3+4. Results: The proportion with a screen-positive MRI (score 3-5) was higher than the proportion with a screen-positive PSA (72/406, 17.7%[95%CI 14.3-21.8] vs. 40/406,9.9%[95%CI 7.3-13.2]; p<0.001). The proportion with a screen-positive ultrasound (score 3-5) was also higher than PSA (96/405, 23.7% [95%CI 19.8-28.1];p<0.001). For an imaging threshold of score 4-5, the proportion with a screen-positive MRI was similar to PSA (43/406, 10.6%[95%CI 7.9-13.2];p=0.71), as was the proportion with a screen-positive ultrasound (52/405, 12.8%[95%CI 9.9-16.5
Kenkre J, Ahmed A, Purkayastha S, et al., 2021, Who will benefit from bariatric surgery for diabetes? A protocol for an observational cohort study, BMJ Open, Vol: 11, ISSN: 2044-6055
Introduction Type 2 diabetes mellitus (T2DM) and obesity are pandemic diseases that lead to a great deal of morbidity and mortality. The most effective treatment for obesity and T2DM is bariatric or metabolic surgery; it can lead to long-term diabetes remission with 4 in 10 of those undergoing surgery having normal blood glucose on no medication 1 year postoperatively. However, surgery carries risks and, additionally, due to resource limitations, there is a restricted number of patients who can access this treatment. Moreover, not all those who undertake surgery respond equally well metabolically. The objective of the current research is to prospectively investigate predictors of T2DM response following metabolic surgery, including those directly involved in its aetiopathogenesis such as fat distribution and genetic variants. This will inform development of a clinically applicable model to help prioritise this therapy to those predicted to have remission.Methods and analysis A prospective multicentre observational cohort study of adult patients with T2DM and obesity undergoing Roux-en-Y gastric bypass surgery. Patients will be comprehensively assessed before surgery to determine their clinical, metabolic, psychological, genetic and fat distribution profiles. A multivariate logistic regression model will be used to assess the value of the factors derived from the preoperative assessment in terms of prediction of diabetes remission.Ethics and dissemination Formal ethics review was undertaken with a favourable opinion (UK HRA RES reference number 18/LO/0931). The dissemination plan is to present the results at conferences, in peer-reviewed journals as well as to lay media and to patient organisations.Trial registration details ClinicalTrials.gov, Identifier: NCT03842475.
Tan T, Khoo B, Mills EG, et al., 2020, Cortisol concentrations and mortality from COVID-19 - Authors' reply, The Lancet Diabetes and Endocrinology, Vol: 8, Pages: 809-810, ISSN: 2213-8595
Tan T, Khoo B, Mills EG, et al., 2020, Association between high serum total cortisol concentrations and mortality from COVID-19, The Lancet Diabetes and Endocrinology, Vol: 8, Pages: 659-660, ISSN: 2213-8595
Proctor J, Naughton F, Sloan M, et al., 2020, Assessment of the Effectiveness and Cost-Effectiveness of Tailored Web-and Text-Based Smoking Cessation Support in Primary Care (iQuit in Practice II): Protocol for a Randomized Controlled Trial, JMIR RESEARCH PROTOCOLS, Vol: 9, ISSN: 1929-0748
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- Citations: 2
Sivaprasad S, Raman R, Conroy D, et al., 2020, The ORNATE India Project: United Kingdom-India Research Collaboration to tackle visual impairment due to diabetic retinopathy, EYE, Vol: 34, Pages: 1279-1286, ISSN: 0950-222X
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- Citations: 15
Reddy D, Shah TT, Dudderidge T, et al., 2020, Comparative Healthcare Research Outcomes of Novel Surgery in prostate cancer (IP4-CHRONOS): A prospective, multi-centre therapeutic phase II parallel Randomised Control Trial, CONTEMPORARY CLINICAL TRIALS, Vol: 93, ISSN: 1551-7144
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- Citations: 15
Farne H, Glanville N, Johnson N, et al., 2020, The CRTH2 Antagonist Timapiprant Does Not Alter the Response Rhinovirus Infection in Asthma: A Randomized, Placebo-Controlled Trial, International Conference of the American-Thoracic-Society, Publisher: AMER THORACIC SOC, ISSN: 1073-449X
Kassavou A, Mirzaei V, Brimicombe J, et al., 2020, A Highly Tailored Text and Voice Messaging Intervention to Improve Medication Adherence in Patients With Either or Both Hypertension and Type 2 Diabetes in a UK Primary Care Setting: Feasibility Randomized Controlled Trial of Clinical Effectiveness, JOURNAL OF MEDICAL INTERNET RESEARCH, Vol: 22, ISSN: 1438-8871
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- Citations: 12
Hardeman W, Mitchell J, Pears S, et al., 2020, Evaluation of a very brief pedometer-based physical activity intervention delivered in NHS Health Checks in England: The VBI randomised controlled trial, PLOS MEDICINE, Vol: 17, ISSN: 1549-1277
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- Citations: 9
Sivaprasad S, Raman R, Rajalakshmi R, et al., 2020, Protocol on a multicentre statistical and economic modelling study of risk-based stratified and personalised screening for diabetes and its complications in India (SMART India), BMJ OPEN, Vol: 10, ISSN: 2044-6055
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- Citations: 10
Jawad S, Modi N, Prevost AT, et al., 2019, A systematic review identifying common data items in neonatal trials and assessing their completeness in routinely recorded United Kingdom national neonatal data, Trials, Vol: 20, ISSN: 1745-6215
BackgroundWe aimed to test whether a common set of key data items reported across high impact neonatal clinical trials could be identified, and to quantify their completeness in routinely recorded United Kingdom neonatal data held in the National Neonatal Research Database (NNRD). MethodsWe systematically reviewed neonatal clinical trials published in four high impact medical journals over 10 years (2006-2015) and extracted baseline characteristics, stratification items, and potential confounders used to adjust primary outcomes. Completeness was examined using data held in the NNRD for identified data items, for infants admitted to neonatal units in 2015. The NNRD is a repository of routinely recorded data extracted from neonatal Electronic Patient Records (EPR) of all admissions to National Health Service (NHS) Neonatal Units in England, Wales and Scotland. We defined missing data as an empty field or an implausible value. We reported common data items as frequencies and percentages alongside percentages of completeness. ResultsWe identified 44 studies involving 32,095 infants and 126 data items. Fourteen data items were reported by more than 20% of studies (table 2). Gestational age (95%), sex (93%) and birth weight (91%) were the most common baseline data items. The completeness of data in the NNRD was high for these data with greater than 90% completeness found for 9 of the 14 most common items.Conclusion High impact neonatal clinical trials share common data items. In the United Kingdom, these items can be obtained at a high level of completeness from routinely recorded data held in the NNRD. The feasibility and efficiency using routinely recorded EPR data, such as that held in the NNRD, for clinical trials, rather than collecting these items anew, should be examined.
Proctor J, Naughton F, Sloan M, et al., 2019, Assessment of the Effectiveness and Cost-Effectiveness of Tailored Web- and Text-Based Smoking Cessation Support in Primary Care (iQuit in Practice II): Protocol for a Randomized Controlled Trial (Preprint)
<sec> <title>BACKGROUND</title> <p>The prevalence of smoking is declining; however, it continues to be a major public health burden. In England, primary care is the health setting that provides smoking cessation support to most smokers. However, this setting has one of the lowest success rates. The iQuit in practice intervention (iQuit) is a tailored web-based and text message intervention developed for use in primary care consultations as an adjunct to routine smoking cessation support with the aim of increasing success rates. iQuit has demonstrated feasibility, acceptability, and potential effectiveness.</p> </sec> <sec> <title>OBJECTIVE</title> <p>This definitive trial aims to determine the effectiveness and cost-effectiveness of iQuit when used as an adjunct to the usual support provided to patients who wish to quit smoking, compared with usual care alone.</p> </sec> <sec> <title>METHODS</title> <p>The iQuit in Practice II trial is a two-arm, parallel-group, randomized controlled trial (RCT) with a 1:1 individual allocation comparing usual care (ie, pharmacotherapy combined with multisession behavioral support)—the control—with usual care plus iQuit—the intervention. Participants were recruited through primary care clinics and talked to a smoking cessation advisor. Participants were randomized during the initial consultation, and those allocated to the intervention group received a tailored advice report and 90 days of text messaging in addition to the standard support provided to all patients.</p> </sec> <sec> <title>RESULTS</title>
Hykin P, Prevost AT, Vasconcelos JC, et al., 2019, Clinical Effectiveness of Intravitreal Therapy With Ranibizumab vs Aflibercept vs Bevacizumab for Macular Edema Secondary to Central Retinal Vein Occlusion A Randomized Clinical Trial, JAMA OPHTHALMOLOGY, Vol: 137, Pages: 1256-1264, ISSN: 2168-6165
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- Citations: 69
Kassavou A, Mirzaei V, Brimicombe J, et al., 2019, A Highly Tailored Text and Voice Messaging Intervention to Improve Medication Adherence in Patients With Either or Both Hypertension and Type 2 Diabetes in a UK Primary Care Setting: Feasibility Randomized Controlled Trial of Clinical Effectiveness (Preprint)
<sec> <title>BACKGROUND</title> <p>The efficacy of a highly tailored digital intervention to support medication adherence and feasibility to support clinical effectiveness as an adjunct to the primary care setting has not been evaluated.</p> </sec> <sec> <title>OBJECTIVE</title> <p>This trial aimed to assess the behavioral efficacy of a highly tailored digital intervention to support medication adherence and to evaluate the feasibility of its clinical effectiveness, in patients with either or both hypertension and type 2 diabetes. We also examined quality of life and mechanisms of behavior change. Intervention fidelity, engagement, and satisfaction were also explored.</p> </sec> <sec> <title>METHODS</title> <p>This was a multicenter, individually randomized controlled trial of 2 parallel groups: an intervention group that received a highly tailored text message and interactive voice response intervention for 12 weeks, and a control group that received usual care. Medication adherence was measured using self-reports and assessor-blinded practice records of a repeat prescription. Systolic blood pressure and glucose levels were assessed by nurses blinded to group allocation during practice visits at 3 months follow-up. Questionnaires obtained data to assess intervention mechanisms of action and satisfaction and digital log files captured data to evaluate fidelity and engagement.</p> </sec> <sec> <title>RESULTS</title> <p>A total of 135 nonadherent patients (62/135, 46% female; 122/135, 90.3%; aged above 50 years) were randomly allocated in
Koffman J, Yorganci E, Yi D, et al., 2019, Managing uncertain recovery for patients nearing the end of life in hospital: a mixed-methods feasibility cluster randomised controlled trial of the AMBER care bundle, TRIALS, Vol: 20
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- Citations: 16
Behary P, Tharakan G, Alexiadou K, et al., 2019, Combined GLP-1, oxyntomodulin, and peptide YY improves body weight and glycemia in obesity and prediabetes/type 2 diabetes: a randomized single-blinded placebo controlled study, Diabetes Care, Vol: 42, Pages: 1446-1453, ISSN: 0149-5992
OBJECTIVE: Roux-en-Y gastric bypass (RYGB) augments postprandial secretion of glucagon-like peptide 1 (GLP-1), oxyntomodulin (OXM), and peptide YY (PYY). Subcutaneous infusion of these hormones ("GOP"), mimicking postprandial levels, reduces energy intake. Our objective was to study the effects of GOP on glycemia and body weight when given for 4 weeks to patients with diabetes and obesity. RESEARCH DESIGN AND METHODS: In this single-blinded mechanistic study, obese patients with prediabetes/diabetes were randomized to GOP (n = 15) or saline (n = 11) infusion for 4 weeks. We also studied 21 patients who had undergone RYGB and 22 patients who followed a very low-calorie diet (VLCD) as unblinded comparators. Outcomes measured were 1) body weight, 2) fructosamine levels, 3) glucose and insulin during a mixed meal test (MMT), 4) energy expenditure (EE), 5) energy intake (EI), and 6) mean glucose and measures of glucose variability during continuous glucose monitoring. RESULTS: GOP infusion was well tolerated over the 4-week period. There was a greater weight loss (P = 0.025) with GOP (mean change -4.4 [95% CI -5.3, -3.5] kg) versus saline (-2.5 [-4.1, -0.9] kg). GOP led to a greater improvement (P = 0.0026) in fructosamine (-44.1 [-62.7, -25.5] µmol/L) versus saline (-11.7 [-18.9, -4.5] µmol/L). Despite a smaller weight loss compared with RYGB and VLCD, GOP led to superior glucose tolerance after a mixed-meal stimulus and reduced glycemic variability compared with RYGB and VLCD. CONCLUSIONS: GOP infusion improves glycemia and reduces body weight. It achieves superior glucose tolerance and reduced glucose variability compared with RYGB and VLCD. GOP is a viable alternative for the treatment of diabetes with favorable effects on body weight.
Al-Laith M, Jasenecova M, Abraham S, et al., 2019, Arthritis prevention in the pre-clinical phase of RA with abatacept (the APIPPRA study): a multi-centre, randomised, double-blind, parallel-group, placebo-controlled clinical trial protocol, Trials, Vol: 20, ISSN: 1745-6215
Trial designWe present a study protocol for a multi-centre, randomised, double-blind, parallel-group, placebo-controlled trial that seeks to test the feasibility, acceptability and effectiveness of a 52-week period of treatment with the first-in-class co-stimulatory blocker abatacept for preventing or delaying the onset of inflammatory arthritis.MethodsThe study aimed to recruit 206 male or female subjects from the secondary care hospital setting across the UK and the Netherlands. Participants who were at least 18 years old, who reported inflammatory sounding joint pain (clinically suspicious arthralgia) and who were found to be positive for serum autoantibodies associated with rheumatoid arthritis (RA) were eligible for enrolment. All study subjects were randomly assigned to receive weekly injections of investigational medicinal product, either abatacept or placebo treatment over the course of a 52-week period. Participants were followed up for a further 52 weeks. The primary endpoint was defined as the time to development of at least three swollen joints or to the fulfilment of the 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria for RA using swollen but not tender joints, whichever endpoint was met first. In either case, swollen joints were confirmed by ultrasonography. Participants, care givers, and those assessing the outcomes were all blinded to group assignment. Clinical assessors and ultrasonographers were also blinded to each other’s assessments for the duration of the study.ConclusionsThere is limited experience of the design and implementation of trials for the prevention of inflammatory joint diseases. We discuss the rationale behind choice and duration of treatment and the challenges associated with defining the “at risk” state and offer pragmatic solutions in the protocol to enrolling subjects at risk of RA.
Santhakumaran S, Gordon AC, Prevost A, et al., 2019, Heterogeneity of treatment effect by baseline risk of mortality in critically ill patients: re-analysis of three recent sepsis and ARDS randomised controlled trials, Critical Care, Vol: 23, ISSN: 1364-8535
BackgroundRandomised controlled trials (RCTs) enrolling patients with sepsis or acute respiratory distress syndrome (ARDS) generate heterogeneous trial populations. Non-random variation in the treatment effect of an intervention due to differences in the baseline risk of death between patients in a population represents one form of heterogeneity of treatment effect (HTE). We assessed whether HTE in two sepsis and one ARDS RCTs could explain indeterminate trial results and inform future trial design.MethodsWe assessed HTE for vasopressin, hydrocortisone and levosimendan in sepsis and simvastatin in ARDS patients, on 28-day mortality, using the total Acute Physiology And Chronic Health Evaluation II (APACHE II) score as the baseline risk measurement, comparing above (high) and below (low) the median score. Secondary risk measures were the acute physiology component of APACHE II and predicted risk of mortality using the APACHE II score. HTE was quantified both in additive (difference in risk difference (RD)) and multiplicative (ratio of relative risks (RR)) scales using estimated treatment differences from a logistic regression model with treatment risk as the interaction term.ResultsThe ratio of the odds of death in the highest APACHE II quartile was 4.9 to 7.4 times compared to the lowest quartile, across the three trials. We did not observe HTE for vasopressin, hydrocortisone and levosimendan in the two sepsis trials. In the HARP-2 trial, simvastatin reduced mortality in the low APACHE II group and increased mortality in the high APACHE II group (difference in RD = 0.34 (0.12, 0.55) (p = 0.02); ratio of RR 3.57 (1.77, 7.17) (p < 0.001). The HTE patterns were inconsistent across the secondary risk measures. The sensitivity analyses of HTE effects for vasopressin, hydrocortisone and levosimendan were consistent with the main analyses and attenuated for simvastatin.ConclusionsWe assessed HTE in three recent ICU RCTs, using m
Goldberg R, Scotta C, Cooper D, et al., 2019, Correction of defective T-regulatory cells from patients with Crohn's disease by Ex Vivo ligation of retinoic acid receptor alpha, Gastroenterology, Vol: 156, Pages: 1775-1787, ISSN: 0016-5085
BACKGROUND & AIMS: Crohn's disease (CD) is characterized by an imbalance of effector and regulatory T cells in the intestinal mucosa. The efficacy of anti-adhesion therapies led us to investigate whether impaired trafficking of T-regulatory (Treg) cells contributes to the pathogenesis of CD. We also investigated whether proper function could be restored to Treg cells by ex vivo expansion in the presence of factors that activate their regulatory activities. METHODS: We measured levels of the integrin α4β7 on Treg cells isolated from peripheral blood or lamina propria of patients with CD and healthy individuals (controls). Treg cells were expanded ex vivo and incubated with rapamycin with or without agonists of the retinoic acid receptor alpha (RARA) and their gene expression profiles were analyzed. We also studied the cells in cytokine challenge, suppression, and flow chamber assays and in SCID mice with human intestinal xenografts. RESULTS: We found that Treg cells from patients with CD express lower levels of the integrin α4β7 than Treg cells from control patients. The pathway that regulates expression of integrin subunit alpha is induced by retinoic acid (RA). Treg cells from patients with CD incubated with rapamycin and an agonist of RARA (RAR568) expressed high levels of integrin α4β7, as well as CD62L and FOXP3, compared to cells incubated with rapamycin or rapamycin and ATRA. These Treg cells had increased suppressive activities in assays and migrated under conditions of shear flow; they did not produce inflammatory cytokines and RAR568 had no effect on cell stability or lineage commitment. Fluorescently labelled Treg cells incubated with RAR568 were significantly more likely to traffic to intestinal xenografts than Treg cells expanded in control medium. CONCLUSIONS: Treg cells from patients with CD express lower levels of the integrin α4β7 than Treg cells from control patients. Incubation of patients' ex vivo ex
Gulliford MC, Juszczyk D, Prevost AT, et al., 2019, Electronically delivered interventions to reduce antibiotic prescribing for respiratory infections in primary care: cluster RCT using electronic health records and cohort study., Health Technology Assessment, Vol: 23, ISSN: 1366-5278
BACKGROUND: Unnecessary prescribing of antibiotics in primary care is contributing to the emergence of antimicrobial drug resistance. OBJECTIVES: To develop and evaluate a multicomponent intervention for antimicrobial stewardship in primary care, and to evaluate the safety of reducing antibiotic prescribing for self-limiting respiratory infections (RTIs). INTERVENTIONS: A multicomponent intervention, developed as part of this study, including a webinar, monthly reports of general practice-specific data for antibiotic prescribing and decision support tools to inform appropriate antibiotic prescribing. DESIGN: A parallel-group, cluster randomised controlled trial. SETTING: The trial was conducted in 79 general practices in the UK Clinical Practice Research Datalink (CPRD). PARTICIPANTS: All registered patients were included. MAIN OUTCOME MEASURES: The primary outcome was the rate of antibiotic prescriptions for self-limiting RTIs over the 12-month intervention period. COHORT STUDY: A separate population-based cohort study was conducted in 610 CPRD general practices that were not exposed to the trial interventions. Data were analysed to evaluate safety outcomes for registered patients with 45.5 million person-years of follow-up from 2005 to 2014. RESULTS: There were 41 intervention trial arm practices (323,155 patient-years) and 38 control trial arm practices (259,520 patient-years). There were 98.7 antibiotic prescriptions for RTIs per 1000 patient-years in the intervention trial arm (31,907 antibiotic prescriptions) and 107.6 per 1000 patient-years in the control arm (27,923 antibiotic prescriptions) [adjusted antibiotic-prescribing rate ratio (RR) 0.88, 95% confidence interval (CI) 0.78 to 0.99; p = 0.040]. There was no evidence of effect in children aged < 15 years (RR 0.96, 95% CI 0.82 to 1.12) or adults aged ≥ 85 years (RR 0.97, 95% CI 0.79 to 1.18). Antibiotic prescribing was reduced in adults aged between 15 and 84 years (RR 0.
Gulliford M, Prevost A, Charlton J, et al., 2019, Effectiveness and safety of electronically-delivered prescribing feedback and decision support on antibiotic utilisation for respiratory illness in primary care. REDUCE cluster-randomised trial, BMJ, Vol: 364, ISSN: 0959-8138
Objectives To evaluate the effectiveness and safety at population scale of electronically delivered prescribing feedback and decision support interventions at reducing antibiotic prescribing for self limiting respiratory tract infections.Design Open label, two arm, cluster randomised controlled trial.Setting UK general practices in the Clinical Practice Research Datalink, randomised between 11 November 2015 and 9 August 2016, with final follow-up on 9 August 2017.Participants 79 general practices (582 675 patient years) randomised (1:1) to antimicrobial stewardship (AMS) intervention or usual care.Interventions AMS intervention comprised a brief training webinar, automated monthly feedback reports of antibiotic prescribing, and electronic decision support tools to inform appropriate prescribing over 12 months. Intervention components were delivered electronically, supported by a local practice champion nominated for the trial.Main outcome measures Primary outcome was the rate of antibiotic prescriptions for respiratory tract infections from electronic health records. Serious bacterial complications were evaluated for safety. Analysis was by Poisson regression with general practice as a random effect, adjusting for covariates. Prespecified subgroup analyses by age group were reported.Results The trial included 41 AMS practices (323 155 patient years) and 38 usual care practices (259 520 patient years). Unadjusted and adjusted rate ratios for antibiotic prescribing were 0.89 (95% confidence interval 0.68 to 1.16) and 0.88 (0.78 to 0.99, P=0.04), respectively, with prescribing rates of 98.7 per 1000 patient years for AMS (31 907 prescriptions) and 107.6 per 1000 patient years for usual care (27 923 prescriptions). Antibiotic prescribing was reduced most in adults aged 15-84 years (adjusted rate ratio 0.84, 95% confidence interval 0.75 to 0.95), with one antibiotic prescription per year avoided for every 62 patients (95% confide
Sivaprasad S, Hykin P, Prevost AT, et al., 2018, Intravitreal aflibercept compared with panretinal photocoagulation for proliferative diabetic retinopathy: the CLARITY non-inferiority RCT, Efficacy and Mechanism Evaluation, Vol: 5, ISSN: 2050-4365
Panretinal photocoagulation (PRP) has been the standard of care for patients with proliferative diabetic retinopathy (PDR) for the last 40 years. It prevents severe visual loss in PDR but is also associated with adverse effects on visual functions.The clinical efficacy and mechanistic evaluation of aflibercept for proliferative diabetic retinopathy (CLARITY) trial evaluated the clinical efficacy, mechanisms and cost-effectiveness of intravitreal aflibercept (Eylea®, Regeneron, Tarrytown, NY, USA/Bayer Pharma AG, Berlin, Germany therapy for PDR.A multicentre, prospective, individually randomised, single-masked, active-controlled trial with concurrent economic evaluation that tested the non-inferiority of intravitreal aflibercept versus standard care PRP at 52 weeks. A subset of the participants enrolled in a mechanistic evaluation substudy.22 UK NHS clinical sites.Patients aged at least 18 years having either treatment-naive PDR or active retinal neovascularisation (NV) despite prior PRP requiring treatment and best corrected visual acuity (BCVA) of 54 Early Treatment Diabetic Retinopathy Study (ETDRS) letters or better in the study eye were included. Eyes with evidence of macular oedema at baseline confirmed by central subfield thickness > 320 µm on spectral-domain optical coherence tomography were excluded.In the intervention arm, intravitreal aflibercept injections were given at baseline, 4 and 8 weeks and patients were subsequently reviewed every month and injected pro re nata based on the treatment response defined by degree of regression of retinal NV. In the comparator arm, PRP was completed in 2-weekly sessions and then supplemented if necessary at 8-weekly intervals.The primary outcome was the mean change in BCVA at 52 weeks utilising a linear mixed-effects model incorporating data from both week 12 and week 52.A total of 232 participants (116 per arm) were recruited between August 2014 and November 2015. A total of 221 and 210 par
Nicholson L, Crosby-Nwaobi R, Vasconcelos JC, et al., 2018, Mechanistic evaluation of panretinal photocoagulation versus aflibercept in proliferative diabetic retinopathy: CLARITY substudy, Investigative Ophthalmology & Visual Science, Vol: 59, Pages: 4277-4284, ISSN: 1552-5783
Purpose: The purpose of this study was to study the effects of panretinal photocoagulation (PRP) and intravitreal aflibercept on retinal vessel oxygen saturations, area of retinal nonperfusion, and area of neovascularization in proliferative diabetic retinopathy.Methods: This is a prospective randomized single center study. Forty patients with proliferative diabetic retinopathy were randomized to PRP or intravitreal aflibercept treatment for 52 weeks. Retinal oximetry and ultra-widefield angiography were performed at baseline and week 52. Ultra-widefield color fundus imaging was performed at baseline, week 12, and week 52. The outcomes were retinal arterio-venous oximetry differences (AVD), area of retinal nonperfusion, and area of neovascularization in disc areas (DA).Results: The AVD in the PRP group increased from 36.7% at baseline to 39.7%, whereas it decreased from 33.4% to 32.5% in the aflibercept group. The difference in AVD between groups at week 52 was 4.0% (95% confidence interval, −0.08, 8.8; P = 0.10). The baseline mean area of retinal nonperfusion of 125.1 DA and 131.2 DA in the PRP and aflibercept groups increased to 156.1 DA and 158.4 DA, respectively, at week 52 (P = 0.46). The median baseline area of neovascularization decreased from 0.98 DA to 0.68 DA in the PRP group and from 0.70 DA to 0 DA in the aflibercept group at week 12 (P = 0.019). At week 52, this measured 0.24 DA in the PRP group and 0 DA in the aflibercept group (P = 0.45).Conclusions: Intravitreal aflibercept achieved an earlier and complete regression of neovascularization in proliferative diabetic retinopathy compared with PRP. There were no significant differences in global change in intravascular oxygen saturation or areas of retinal nonperfusion between the two groups by 52 weeks.
Sivaprasad S, Vasconcelos JC, Prevost AT, et al., 2018, Clinical efficacy and safety of a light mask for prevention of dark adaptation in treating and preventing progression of early diabetic macular oedema at 24 months (CLEOPATRA): a multicentre, phase 3, randomised controlled trial, Lancet Diabetes and Endocrinology, Vol: 6, Pages: 382-391, ISSN: 2213-8595
BackgroundWe aimed to assess 24-month outcomes of wearing an organic light-emitting sleep mask as an intervention to treat and prevent progression of non-central diabetic macular oedema.MethodsCLEOPATRA was a phase 3, single-blind, parallel-group, randomised controlled trial undertaken at 15 ophthalmic centres in the UK. Adults with non-centre-involving diabetic macular oedema were randomly assigned (1:1) to wearing either a light mask during sleep (Noctura 400 Sleep Mask, PolyPhotonix Medical, Sedgefield, UK) or a sham (non-light) mask, for 24 months. Randomisation was by minimisation generated by a central web-based computer system. Outcome assessors were masked technicians and optometrists. The primary outcome was the change in maximum retinal thickness on optical coherence tomography (OCT) at 24 months, analysed using a linear mixed-effects model incorporating 4-monthly measurements and baseline adjustment. Analysis was done using the intention-to-treat principle in all randomised patients with OCT data. Safety was assessed in all patients. This trial is registered with Controlled-Trials.com, number ISRCTN85596558.FindingsBetween April 10, 2014, and June 15, 2015, 308 patients were randomly assigned to wearing the light mask (n=155) or a sham mask (n=153). 277 patients (144 assigned the light mask and 133 the sham mask) contributed to the mixed-effects model over time, including 246 patients with OCT data at 24 months. The change in maximum retinal thickness at 24 months did not differ between treatment groups (mean change −9·2 μm [SE 2·5] for the light mask vs −12·9 μm [SE 2·9] for the sham mask; adjusted mean difference −0·65 μm, 95% CI −6·90 to 5·59; p=0·84). Median compliance with wearing the light mask at 24 months was 19·5% (IQR 1·9–51·6). No serious adverse events were related to either mask. The most frequent adverse events related to the a
Crocketta RA, King SE, Marteau TM, et al., 2018, Nutritional labelling for healthier food or non-alcoholic drink purchasing and consumption, Cochrane Database of Systematic Reviews, Vol: 2, ISSN: 1469-493X
BackgroundNutritional labelling is advocated as a means to promote healthier food purchasing and consumption, including lower energy intake. Internationally, many different nutritional labelling schemes have been introduced. There is no consensus on whether such labelling is effective in promoting healthier behaviour.ObjectivesTo assess the impact of nutritional labelling for food and non-alcoholic drinks on purchasing and consumption of healthier items. Our secondary objective was to explore possible effect moderators of nutritional labelling on purchasing and consumption.Search methodsWe searched 13 electronic databases including CENTRAL, MEDLINE and Embase to 26 April 2017. We also handsearched references and citations and sought unpublished studies through websites and trials registries.Selection criteriaEligible studies: were randomised or quasi-randomised controlled trials (RCTs/Q-RCTs), controlled before-and-after studies, or interrupted time series (ITS) studies; compared a labelled product (with information on nutrients or energy) with the same product without a nutritional label; assessed objectively measured purchasing or consumption of foods or non-alcoholic drinks in real-world or laboratory settings.Data collection and analysisTwo authors independently selected studies for inclusion and extracted study data. We applied the Cochrane 'Risk of bias' tool and GRADE to assess the quality of evidence. We pooled studies that evaluated similar interventions and outcomes using a random-effects meta-analysis, and we synthesised data from other studies in a narrative summary.Main resultsWe included 28 studies, comprising 17 RCTs, 5 Q-RCTs and 6 ITS studies. Most (21/28) took place in the USA, and 19 took place in university settings, 14 of which mainly involved university students or staff. Most (20/28) studies assessed the impact of labelling on menus or menu boards, or nutritional labelling placed on, or adjacent to, a range of foods or drinks from which partic
Sivaprasad S, Prevost AT, Vasconcelos J, et al., 2017, Intravitreal aflibercept for proliferative diabetic retinopathy Reply, Lancet, Vol: 390, Pages: 2141-2142, ISSN: 0140-6736
Prevost A, 2017, P108: A journey from statistical consultation to funded adaptive trial, 4th International Clinical Trials Methodology Conference, Publisher: BioMed Central, ISSN: 1745-6215
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