Visual Function Questionnaire as an outcome measure for homonymous hemianopia: subscales and supplementary questions, analysis from the VISION trial

Background: We conduct supplementary analyses of the NEI VFQ-25 data to evaluate where changes occurred within subscales of the NEI VFQ-25 leading to change in the composite scores between the three treatment arms, and evaluate the NEI VFQ-25 with and without the Neuro 10 supplement. Methods: A prospective, multicentre, parallel, single-blind, three-arm RCT of fourteen UK acute stroke units was conducted. Stroke survivors with homonymous hemianopia were recruited. Interventions included: Fresnel prisms for minimum 2 h, 5 days/week over 6-weeks (Arm a), Visual search training for minimum 30 min, 5 days/week over 6-weeks (Arm b) and standard care-information only (Arm c). Primary and secondary outcomes (including NEI VFQ-25 data) were measured at baseline, 6, 12 and 26 weeks after randomisation. Results: Eighty seven patients were recruited (69% male; mean age (SD) equal to 69 (12) years). At 26 weeks, outcomes for 24, 24 and 22 patients, respectively, were compared to baseline. NEI VFQ-25 (with and without Neuro 10) responses improved from baseline to 26 weeks with visual search training compared to Fresnel prisms and standard care. In subscale analysis, the most impacted across all treatment arms was ‘driving’ whilst the least impacted were ‘colour vision’ and ‘ocular pain’. Conclusions: Composite scores differed systematically for the NEI VFQ-25 (Neuro 10) versus NEI VFQ-25 at all time points. For subscale scores, descriptive statistics suggest clinically relevant improvement in distance activities and vision-specific dependency subscales for NEI VFQ-25 scores in the visual search treatment arm. Trial Registration: Current Controlled Trials ISRCTN05956042

Enhancing practitioners’ confidence in recruitment and consent in the EcLiPSE trial: A mixed-method evaluation of site training – a Paediatric Emergency Research in the United Kingdom and Ireland (PERUKI) study

Background: EcLiPSE (Emergency treatment with Levetiracetam or Phenytoin in Status Epilepticus in children) is a randomised controlled trial (RCT) in the United Kingdom. Challenges to success include the need to immediately administer an intervention without informed consent and changes in staffing during trial conduct, mainly due to physician rotations. Using literature on parents' perspectives and research without prior consent (RWPC) guidance, we developed an interactive training package (including videos, simulation and question and answer sessions) and evaluated its dissemination and impact upon on practitioners' confidence in recruitment and consent. Methods: Questionnaires were administered before and immediately after training followed by telephone interviews (mean 11 months later), focus groups (mean 14 months later) and an online questionnaire (8 months before trial closure).Results: One hundred and twenty-five practitioners from 26/30 (87%) participating hospitals completed a questionnaire before and after training. We conducted 10 interviews and six focus groups (comprising 36 practitioners); 199 practitioners working in all recruiting hospitals completed the online questionnaire. Before training, practitioners were concerned about recruitment and consent. Confidence increased after training for explaining (all scale 0-5, 95% CIs above 0 and p values < 0.05): the study (66% improved mean score before 3.28 and after 4.52), randomisation (47% improvement, 3.86 to 4.63), RWPC (72% improvement, 2.98 to 4.39), and addressing parents' objections to randomisation (51% improvement, 3.37 to 4.25). Practitioners rated highly the content and clarity of the training, which was successfully disseminated. Some concerns about staff availability for training and consent discussions remained.Conclusions: Training improved practitioners' confidence in recruitment and RWPC. Our findings highlight the value of using parents' perspectives to inform training and to engage practitioners in trials that are at high risk of being too challenging to conduct

Seven-step framework to enhance practitioner explanations and parental understandings of research without prior consent in paediatric emergency and critical care trials

Background: Alternatives to prospective informed consent enable the conduct of paediatric emergency and critical care trials. Research without prior consent (RWPC) involves practitioners approaching parents after an intervention has been given and seeking consent for their child to continue in the trial. As part of an embedded study in the 'Emergency treatment with Levetiracetam or Phenytoin in Status Epilepticus in children' (EcLiPSE) trial, we explored how practitioners described the trial and RWPC during recruitment discussions, and how well this information was understood by parents. We aimed to develop a framework to assist trial conversations in future paediatric emergency and critical care trials using RWPC. Methods: Qualitative methods embedded within the EcLiPSE trial processes, including audiorecorded practitioner-parent trial discussions and telephone interviews with parents. We analysed data using thematic analysis, drawing on the Realpe et al (2016) model for recruitment to trials. Results: We analysed 76 recorded trial discussions and conducted 30 parent telephone interviews. For 19 parents, we had recorded trial discussion and interview data, which were matched for analysis. Parental understanding of the EcLiPSE trial was enhanced when practitioners: provided a comprehensive description of trial aims; explained the reasons for RWPC; discussed uncertainty about which intervention was best; provided a balanced description of trial intervention; provided a clear explanation about randomisation and provided an opportunity for questions. We present a seven-step framework to assist recruitment practice in trials involving RWPC. Conclusion: This study provides a framework to enhance recruitment practice and parental understanding in paediatric emergency and critical care trials involving RWPC. Further testing of this framework is required

Antimicrobial-impregnated central venous catheters for prevention of neonatal bloodstream infection (PREVAIL) : an open-label, parallel-group, pragmatic, randomised controlled trial

BACKGROUND: Bloodstream infection is associated with high mortality and serious morbidity in preterm babies. Evidence from clinical trials shows that antimicrobial-impregnated central venous catheters (CVCs) reduce catheter-related bloodstream infection in adults and children receiving intensive care, but there is a paucity of similar evidence for babies receiving neonatal intensive care. METHODS: This open-label, parallel-group, pragmatic, randomised controlled trial was done in 18 neonatal intensive care units in England. Newborn babies who needed a peripherally inserted CVC (PICC) were allocated randomly (1:1) to receive either a PICC impregnated with miconazole and rifampicin or a standard (non-antimicrobial-impregnated) PICC. Random allocation was done with a web-based program, which was centrally controlled to ensure allocation concealment. Randomisation sequences were computer-generated in random blocks of two and four, and stratified by site. Masking of clinicians to PICC allocation was impractical because rifampicin caused brown staining of the antimicrobial-impregnated PICC. However, participant inclusion in analyses and occurrence of outcome events were determined following an analysis plan that was specified before individuals saw the unblinded data. The primary outcome was the time from random allocation to first microbiologically confirmed bloodstream or cerebrospinal fluid (CSF) infection between 24 h after randomisation and 48 h after PICC removal or death. We analysed outcome data according to the intention-to-treat principle. We excluded babies for whom a PICC was not inserted from safety analyses, as these analyses were done with groups defined by the PICC used. This trial is registered with ISRCTN, number 81931394. FINDINGS: Between Aug 12, 2015, and Jan 11, 2017, we randomly assigned 861 babies (754 [88%] born before 32 weeks of gestation) to receive an antimicrobial-impregnated PICC (430 babies) or standard PICC (431 babies). The median time to PICC removal was 8·20 days (IQR 4·77-12·13) in the antimicrobial-impregnated PICC group versus 7·86 days (5·00-12·53) days in the standard PICC group (hazard ratio [HR] 1·03, 95% CI 0·89-1·18, p=0·73), with 46 (11%) of 430 babies versus 44 (10%) of 431 babies having a microbiologically confirmed bloodstream or CSF infection. The time from random allocation to first bloodstream or CSF infection was similar between the two groups (HR 1·11, 95% CI 0·73-1·67, p=0·63). Secondary outcomes relating to infection, rifampicin resistance in positive blood or CSF cultures, mortality, clinical outcomes at neonatal unit discharge, and time to PICC removal were similar between the two groups, although rifampicin resistance in positive cultures of PICC tips was higher in the antimicrobial-impregnated PICC group (relative risk 3·51, 95% CI 1·16-10·57, p=0·018). 60 adverse events were reported from 49 (13%) patients in the antimicrobial-impregnated PICC group and 50 events from 45 (10%) babies in the standard PICC group. INTERPRETATION: We found no evidence of benefit or harm associated with miconazole and rifampicin-impregnated PICCs compared with standard PICCs for newborn babies. Future research should focus on other types of antimicrobial impregnation of PICCs and alternative approaches for preventing infection. FUNDING: UK National Institute for Health Research Health Technology Assessment programme

Adalimumab in combination with methotrexate for refractory uveitis associated with juvenile idiopathic arthritis: a RCT

Abstract Background Children with juvenile idiopathic arthritis (JIA) are at risk of uveitis. The role of adalimumab (Humira®; AbbVie Inc., Ludwigshafen, Germany) in the management of uveitis in children needs to be determined. Objective To compare the efficacy, safety and cost-effectiveness of adalimumab in combination with methotrexate (MTX) versus placebo with MTX alone, with regard to controlling disease activity in refractory uveitis associated with JIA. Design This was a randomised (applying a ratio of 2 : 1 in favour of adalimumab), double-blind, placebo-controlled, multicentre parallel-group trial with an integrated economic evaluation. A central web-based system used computer-generated tables to allocate treatments. A cost–utility analysis based on visual acuity was conducted and a 10-year extrapolation by Markov modelling was also carried out. Setting The setting was tertiary care centres throughout the UK. Participants Patients aged 2–18 years inclusive, with persistently active JIA-associated uveitis (despite optimised MTX treatment for at least 12 weeks). Interventions All participants received a stable dose of MTX and either adalimumab (20 mg/0.8 ml for patients weighing < 30 kg or 40 mg/0.8 ml for patients weighing ≥ 30 kg by subcutaneous injection every 2 weeks based on body weight) or a placebo (0.8 ml as appropriate according to body weight by subcutaneous injection every 2 weeks) for up to 18 months. A follow-up appointment was arranged at 6 months. Main outcome measures Primary outcome – time to treatment failure [multicomponent score as defined by set criteria based on the Standardisation of Uveitis Nomenclature (SUN) criteria]. Economic outcome – incremental cost per quality-adjusted life-year (QALY) gained from the perspective of the NHS in England and Personal Social Services providers. Full details of secondary outcomes are provided in the study protocol. Results A total of 90 participants were randomised (adalimumab, n = 60; placebo, n = 30). There were 14 (23%) treatment failures in the adalimumab group and 17 (57%) in the placebo group. The analysis of the data from the double-blind phase of the trial showed that the hazard risk (HR) of treatment failure was significantly reduced, by 75%, for participants in the adalimumab group (HR 0.25, 95% confidence interval 0.12 to 0.51; p < 0.0001 from log-rank test). The cost-effectiveness of adalimumab plus MTX was £129,025 per QALY gained. Adalimumab-treated participants had a much higher incidence of adverse and serious adverse events. Conclusions Adalimumab in combination with MTX is safe and effective in the management of JIA-associated uveitis. However, the likelihood of cost-effectiveness is < 1% at the £30,000-per-QALY threshold. Future work A clinical trial is required to define the most effective time to stop therapy. Prognostic biomarkers of early and complete response should also be identified

Levetiracetam as an alternative to phenytoin for second-line emergency treatment of children with convulsive status epilepticus: the EcLiPSE RCT.

BACKGROUND:Convulsive status epilepticus is the most common neurological emergency in children. Its management is important to avoid or minimise neurological morbidity and death. The current first-choice second-line drug is phenytoin (Epanutin, Pfizer Inc., New York, NY, USA), for which there is no robust scientific evidence. OBJECTIVE:To determine whether phenytoin or levetiracetam (Keppra, UCB Pharma, Brussels, Belgium) is the more clinically effective intravenous second-line treatment of paediatric convulsive status epilepticus and to help better inform its management. DESIGN:A multicentre parallel-group randomised open-label superiority trial with a nested mixed-method study to assess recruitment and research without prior consent. SETTING:Participants were recruited from 30 paediatric emergency departments in the UK. PARTICIPANTS:Participants aged 6 months to 17 years 11 months, who were presenting with convulsive status epilepticus and were failing to respond to first-line treatment. INTERVENTIONS:Intravenous levetiracetam (40 mg/kg) or intravenous phenytoin (20 mg/kg). MAIN OUTCOME MEASURES:Primary outcome - time from randomisation to cessation of all visible signs of convulsive status epilepticus. Secondary outcomes - further anticonvulsants to manage the convulsive status epilepticus after the initial agent, the need for rapid sequence induction owing to ongoing convulsive status epilepticus, admission to critical care and serious adverse reactions. RESULTS:Between 17 July 2015 and 7 April 2018, 286 participants were randomised, treated and consented. A total of 152 participants were allocated to receive levetiracetam and 134 participants to receive phenytoin. Convulsive status epilepticus was terminated in 106 (70%) participants who were allocated to levetiracetam and 86 (64%) participants who were allocated to phenytoin. Median time from randomisation to convulsive status epilepticus cessation was 35 (interquartile range 20-not assessable) minutes in the levetiracetam group and 45 (interquartile range 24-not assessable) minutes in the phenytoin group (hazard ratio 1.20, 95% confidence interval 0.91 to 1.60; p = 0.2). Results were robust to prespecified sensitivity analyses, including time from treatment commencement to convulsive status epilepticus termination and competing risks. One phenytoin-treated participant experienced serious adverse reactions. LIMITATIONS:First, this was an open-label trial. A blinded design was considered too complex, in part because of the markedly different infusion rates of the two drugs. Second, there was subjectivity in the assessment of 'cessation of all signs of continuous, rhythmic clonic activity' as the primary outcome, rather than fixed time points to assess convulsive status epilepticus termination. However, site training included simulated demonstration of seizure cessation. Third, the time point of randomisation resulted in convulsive status epilepticus termination prior to administration of trial treatment in some cases. This affected both treatment arms equally and had been prespecified at the design stage. Last, safety measures were a secondary outcome, but the trial was not powered to demonstrate difference in serious adverse reactions between treatment groups. CONCLUSIONS:Levetiracetam was not statistically superior to phenytoin in convulsive status epilepticus termination rate, time taken to terminate convulsive status epilepticus or frequency of serious adverse reactions. The results suggest that it may be an alternative to phenytoin in the second-line management of paediatric convulsive status epilepticus. Simple trial design, bespoke site training and effective leadership were found to facilitate practitioner commitment to the trial and its success. We provide a framework to optimise recruitment discussions in paediatric emergency medicine trials. FUTURE WORK:Future work should include a meta-analysis of published studies and the possible sequential use of levetiracetam and phenytoin or sodium valproate in the second-line treatment of paediatric convulsive status epilepticus. TRIAL REGISTRATION:Current Controlled Trials ISRCTN22567894 and European Clinical Trials Database EudraCT number 2014-002188-13. FUNDING:This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 58. See the NIHR Journals Library website for further project information

Antimicrobial-impregnated central venous catheters for preventing neonatal bloodstream infection : the PREVAIL RCT

BACKGROUND:Clinical trials show that antimicrobial-impregnated central venous catheters reduce catheter-related bloodstream infection in adults and children receiving intensive care, but there is insufficient evidence for use in newborn babies. OBJECTIVES:The objectives were (1) to determine clinical effectiveness by conducting a randomised controlled trial comparing antimicrobial-impregnated peripherally inserted central venous catheters with standard peripherally inserted central venous catheters for reducing bloodstream or cerebrospinal fluid infections (referred to as bloodstream infections); (2) to conduct an economic evaluation of the costs, cost-effectiveness and value of conducting additional research; and (3) to conduct a generalisability analysis of trial findings to neonatal care in the NHS. DESIGN:Three separate studies were undertaken, each addressing one of the three objectives. (1) This was a multicentre, open-label, pragmatic randomised controlled trial; (2) an analysis was undertaken of hospital care costs, lifetime cost-effectiveness and value of information from an NHS perspective; and (3) this was a retrospective cohort study of bloodstream infection rates in neonatal units in England. SETTING:The randomised controlled trial was conducted in 18 neonatal intensive care units in England. PARTICIPANTS:Participants were babies who required a peripherally inserted central venous catheter (of 1 French gauge in size). INTERVENTIONS:The interventions were an antimicrobial-impregnated peripherally inserted central venous catheter (coated with rifampicin-miconazole) or a standard peripherally inserted central venous catheter, allocated randomly (1 : 1) using web randomisation. MAIN OUTCOME MEASURE:Study 1 - time to first bloodstream infection, sampled between 24 hours after randomisation and 48 hours after peripherally inserted central venous catheter removal. Study 2 - cost-effectiveness of the antimicrobial-impregnated peripherally inserted central venous catheter compared with the standard peripherally inserted central venous catheters. Study 3 - risk-adjusted bloodstream rates in the trial compared with those in neonatal units in England. For study 3, the data used were as follows: (1) case report forms and linked death registrations; (2) case report forms and linked death registrations linked to administrative health records with 6-month follow-up; and (3) neonatal health records linked to infection surveillance data. RESULTS:Study 1, clinical effectiveness - 861 babies were randomised (antimicrobial-impregnated peripherally inserted central venous catheter, n = 430; standard peripherally inserted central venous catheter, n = 431). Bloodstream infections occurred in 46 babies (10.7%) randomised to antimicrobial-impregnated peripherally inserted central venous catheters and in 44 (10.2%) babies randomised to standard peripherally inserted central venous catheters. No difference in time to bloodstream infection was detected (hazard ratio 1.11, 95% confidence interval 0.73 to 1.67; p = 0.63). Secondary outcomes of rifampicin resistance in positive blood/cerebrospinal fluid cultures, mortality, clinical outcomes at neonatal unit discharge and time to peripherally inserted central venous catheter removal were similar in both groups. Rifampicin resistance in positive peripherally inserted central venous catheter tip cultures was higher in the antimicrobial-impregnated peripherally inserted central venous catheter group (relative risk 3.51, 95% confidence interval 1.16 to 10.57; p = 0.02) than in the standard peripherally inserted central venous catheter group. Adverse events were similar in both groups. Study 2, economic evaluation - the mean cost of babies' hospital care was £83,473. Antimicrobial-impregnated peripherally inserted central venous catheters were not cost-effective. Given the increased price, compared with standard peripherally inserted central venous catheters, the minimum reduction in risk of bloodstream infection for antimicrobial-impregnated peripherally inserted central venous catheters to be cost-effective was 3% and 15% for babies born at 23-27 and 28-32 weeks' gestation, respectively. Study 3, generalisability analysis - risk-adjusted bloodstream infection rates per 1000 peripherally inserted central venous catheter days were similar among babies in the trial and in all neonatal units. Of all bloodstream infections in babies receiving intensive or high-dependency care in neonatal units, 46% occurred during peripherally inserted central venous catheter days. LIMITATIONS:The trial was open label as antimicrobial-impregnated and standard peripherally inserted central venous catheters are different colours. There was insufficient power to determine differences in rifampicin resistance. CONCLUSIONS:No evidence of benefit or harm was found of peripherally inserted central venous catheters impregnated with rifampicin-miconazole during neonatal care. Interventions with small effects on bloodstream infections could be cost-effective over a child's life course. Findings were generalisable to neonatal units in England. Future research should focus on other types of antimicrobial impregnation of peripherally inserted central venous catheters and alternative approaches for preventing bloodstream infections in neonatal care. TRIAL REGISTRATION:Current Controlled Trials ISRCTN81931394. FUNDING:This project was funded by the National Institute for Health Research Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 57. See the NIHR Journals Library website for further project information

Levetiracetam versus phenytoin for second-line treatment of paediatric convulsive status epilepticus (EcLiPSE): a multicentre, open-label, randomised trial

Background Phenytoin is the recommended second-line intravenous anticonvulsant for treatment of paediatric convulsive status epilepticus in the UK; however, some evidence suggests that levetiracetam could be an effective and safer alternative. This trial compared the efficacy and safety of phenytoin and levetiracetam for second-line management of paediatric convulsive status epilepticus.Methods This open-label, randomised clinical trial was undertaken at 30 UK emergency departments at secondary and tertiary care centres. Participants aged 6 months to under 18 years, with convulsive status epilepticus requiring second-line treatment, were randomly assigned (1:1) using a computer-generated randomisation schedule to receive levetiracetam (40 mg/kg over 5 min) or phenytoin (20 mg/kg over at least 20 min), stratified by centre. The primary outcome was time from randomisation to cessation of convulsive status epilepticus, analysed in the modified intention-to-treat population (excluding those who did not require second-line treatment after randomisation and those who did not provide consent). This trial is registered with ISRCTN, number ISRCTN22567894.Findings Between July 17, 2015, and April 7, 2018, 1432 patients were assessed for eligibility. After exclusion of ineligible patients, 404 patients were randomly assigned. After exclusion of those who did not require second-line treatment and those who did not consent, 286 randomised participants were treated and had available data: 152 allocated to levetiracetam, and 134 to phenytoin. Convulsive status epilepticus was terminated in 106 (70%) children in the levetiracetam group and in 86 (64%) in the phenytoin group. Median time from randomisation to cessation of convulsive status epilepticus was 35 min (IQR 20 to not assessable) in the levetiracetam group and 45 min (24 to not assessable) in the phenytoin group (hazard ratio 1·20, 95% CI 0·91–1·60; p=0·20). One participant who received levetiracetam followed by phenytoin died as a result of catastrophic cerebral oedema unrelated to either treatment. One participant who received phenytoin had serious adverse reactions related to study treatment (hypotension considered to be immediately life-threatening [a serious adverse reaction] and increased focal seizures and decreased consciousness considered to be medically significant [a suspected unexpected serious adverse reaction]). Interpretation Although levetiracetam was not significantly superior to phenytoin, the results, together with previously reported safety profiles and comparative ease of administration of levetiracetam, suggest it could be an appropriate alternative to phenytoin as the first-choice, second-line anticonvulsant in the treatment of paediatric convulsive status epilepticus

Contributions of mean and shape of blood pressure distribution to worldwide trends and variations in raised blood pressure: A pooled analysis of 1018 population-based measurement studies with 88.6 million participants

© The Author(s) 2018. Background: Change in the prevalence of raised blood pressure could be due to both shifts in the entire distribution of blood pressure (representing the combined effects of public health interventions and secular trends) and changes in its high-blood-pressure tail (representing successful clinical interventions to control blood pressure in the hypertensive population). Our aim was to quantify the contributions of these two phenomena to the worldwide trends in the prevalence of raised blood pressure. Methods: We pooled 1018 population-based studies with blood pressure measurements on 88.6 million participants from 1985 to 2016. We first calculated mean systolic blood pressure (SBP), mean diastolic blood pressure (DBP) and prevalence of raised blood pressure by sex and 10-year age group from 20-29 years to 70-79 years in each study, taking into account complex survey design and survey sample weights, where relevant. We used a linear mixed effect model to quantify the association between (probittransformed) prevalence of raised blood pressure and age-group- and sex-specific mean blood pressure. We calculated the contributions of change in mean SBP and DBP, and of change in the prevalence-mean association, to the change in prevalence of raised blood pressure. Results: In 2005-16, at the same level of population mean SBP and DBP, men and women in South Asia and in Central Asia, the Middle East and North Africa would have the highest prevalence of raised blood pressure, and men and women in the highincome Asia Pacific and high-income Western regions would have the lowest. In most region-sex-age groups where the prevalence of raised blood pressure declined, one half or more of the decline was due to the decline in mean blood pressure. Where prevalence of raised blood pressure has increased, the change was entirely driven by increasing mean blood pressure, offset partly by the change in the prevalence-mean association. Conclusions: Change in mean blood pressure is the main driver of the worldwide change in the prevalence of raised blood pressure, but change in the high-blood-pressure tail of the distribution has also contributed to the change in prevalence, especially in older age groups

Repositioning of the global epicentre of non-optimal cholesterol

High blood cholesterol is typically considered a feature of wealthy western countries(1,2). However, dietary and behavioural determinants of blood cholesterol are changing rapidly throughout the world(3) and countries are using lipid-lowering medications at varying rates. These changes can have distinct effects on the levels of high-density lipoprotein (HDL) cholesterol and non-HDL cholesterol, which have different effects on human health(4,5). However, the trends of HDL and non-HDL cholesterol levels over time have not been previously reported in a global analysis. Here we pooled 1,127 population-based studies that measured blood lipids in 102.6 million individuals aged 18 years and older to estimate trends from 1980 to 2018 in mean total, non-HDL and HDL cholesterol levels for 200 countries. Globally, there was little change in total or non-HDL cholesterol from 1980 to 2018. This was a net effect of increases in low- and middle-income countries, especially in east and southeast Asia, and decreases in high-income western countries, especially those in northwestern Europe, and in central and eastern Europe. As a result, countries with the highest level of non-HDL cholesterol-which is a marker of cardiovascular riskchanged from those in western Europe such as Belgium, Finland, Greenland, Iceland, Norway, Sweden, Switzerland and Malta in 1980 to those in Asia and the Pacific, such as Tokelau, Malaysia, The Philippines and Thailand. In 2017, high non-HDL cholesterol was responsible for an estimated 3.9 million (95% credible interval 3.7 million-4.2 million) worldwide deaths, half of which occurred in east, southeast and south Asia. The global repositioning of lipid-related risk, with non-optimal cholesterol shifting from a distinct feature of high-income countries in northwestern Europe, north America and Australasia to one that affects countries in east and southeast Asia and Oceania should motivate the use of population-based policies and personal interventions to improve nutrition and enhance access to treatment throughout the world.Peer reviewe