Imperial College London

Emeritus ProfessorJohnWarner

Faculty of MedicineNational Heart & Lung Institute

Emeritus in Paediatrics
 
 
 
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j.o.warner

 
 
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Location

 

246Medical SchoolSt Mary's Campus

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Summary

 

Publications

Publication Type
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754 results found

Warner JO, 2021, Translating results from research into clinical practice., Arch Dis Child

Journal article

Munblit D, Bobkova P, Spiridonova E, Shikhaleva A, Gamirova A, Blyuss O, Nekliudov N, Bugaeva P, Andreeva M, DunnGalvin A, Comberiati P, Apfelbacher C, Genuneit J, Avdeev S, Kapustina V, Guekht A, Fomin V, Svistunov AA, Timashev P, Subbot VS, Royuk VV, Drake TM, Hanson SW, Merson L, Carson G, Horby P, Sigfrid L, Scott JT, Semple MG, Warner JO, Vos T, Olliaro P, Glybochko P, Butnaru Det al., 2021, Incidence and risk factors for persistent symptoms in adults previously hospitalized for COVID-19, CLINICAL AND EXPERIMENTAL ALLERGY, ISSN: 0954-7894

Journal article

Munblit D, Sigfrid L, Warner JO, 2021, Setting Priorities to Address Research Gaps in Long-term COVID-19 Outcomes in Children, JAMA PEDIATRICS, ISSN: 2168-6203

Journal article

Munblit D, Nekliudov NA, Bugaeva P, Blyuss O, Kislova M, Listovskaya E, Gamirova A, Shikhaleva A, Belyaev V, Timashev P, Warner JO, Comberiati P, Apfelbacher C, Bezrukov E, Politov ME, Yavorovskiy A, Bulanova E, Tsareva N, Avdeev S, Kapustina VA, Pigolkin YI, Dankwa EA, Kartsonaki C, Pritchard MG, Victor F, Svistunov AA, Butnaru D, Glybochko Pet al., 2021, StopCOVID cohort: An observational study of 3,480 patients admitted to the Sechenov University hospital network in Moscow city for suspected COVID-19 infection, Clinical Infectious Diseases, Vol: 73, Pages: 1-11, ISSN: 1058-4838

BACKGROUND: The epidemiology, clinical course, and outcomes of COVID-19 patients in the Russian population are unknown. Information on the differences between laboratory-confirmed and clinically-diagnosed COVID-19 in real-life settings is lacking. METHODS: We extracted data from the medical records of adult patients who were consecutively admitted for suspected COVID-19 infection in Moscow, between April 8 and May 28, 2020. RESULTS: Of the 4261 patients hospitalised for suspected COVID-19, outcomes were available for 3480 patients (median age 56 years (interquartile range 45-66). The commonest comorbidities were hypertension, obesity, chronic cardiac disease and diabetes. Half of the patients (n=1728) had a positive RT-PCR while 1748 were negative on RT-PCR but had clinical symptoms and characteristic CT signs suggestive of COVID-19 infection.No significant differences in frequency of symptoms, laboratory test results and risk factors for in-hospital mortality were found between those exclusively clinically diagnosed or with positive SARS-CoV-2 RT-PCR.In a multivariable logistic regression model the following were associated with in-hospital mortality; older age (per 1 year increase) odds ratio [OR] 1.05 (95% confidence interval (CI) 1.03 - 1.06); male sex (OR 1.71, 1.24 - 2.37); chronic kidney disease (OR 2.99, 1.89 - 4.64); diabetes (OR 2.1, 1.46 - 2.99); chronic cardiac disease (OR 1.78, 1.24 - 2.57) and dementia (OR 2.73, 1.34 - 5.47). CONCLUSIONS: Age, male sex, and chronic comorbidities were risk factors for in-hospital mortality. The combination of clinical features were sufficient to diagnoseCOVID-19 infection indicating that laboratory testing is not critical in real-life clinical practice.

Journal article

Osmanov IM, Spiridonova E, Bobkova P, Gamirova A, Shikhaleva A, Andreeva M, Blyuss O, El-Taravi Y, DunnGalvin A, Comberiati P, Peroni DG, Apfelbacher C, Genuneit J, Mazankova L, Miroshina A, Chistyakova E, Samitova E, Borzakova S, Bondarenko E, Korsunskiy AA, Konova I, Hanson SW, Carson G, Sigfrid L, Scott JT, Greenhawt M, Whittaker EA, Garralda E, Swann O, Buonsenso D, Nicholls DE, Simpson F, Jones C, Semple MG, Warner JO, Vos T, Olliaro P, Munblit D, Sechenov StopCOVID Research Teamet al., 2021, Risk factors for long covid in previoulsy hospitalsied children using the ISARIC Global Follow-Up Protocol: a prospective cohort study, European Respiratory Journal, ISSN: 0903-1936

Background The long-term sequelae of coronavirus disease 2019 (Covid-19) in children remain poorly characterised. This study aimed to assess long-term outcomes in children previously hospitalised with Covid-19 and associated risk factors.Methods This is a prospective cohort study of children (≤18 years old) admitted with confirmed Covid-19. Children admitted to the hospital between April 2, 2020 and August 26, 2020, were included. Telephone interview using the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) Covid-19 Health and Wellbeing paediatric follow-up survey. Persistent symptoms (>5 months) were further categorised by system(s) involved.Findings 518 of 853 (61%) of eligible children were available for the follow-up assessment and included in the study. Median age was 10.4 years (IQR, 3–15.2) and 270 (52.1%) were girls; median follow-up since hospital discharge was 256 (223–271) days. At the time of the follow-up interview 126 (24.3%) participants reported persistent symptoms among which fatigue (53, 10.7%), sleep disturbance (36, 6.9%,) and sensory problems (29, 5.6%) were the most common. Multiple symptoms were experienced by 44 (8.4%) participants. Risk factors for persistent symptoms were: older age “6–11 years” (odds ratio 2.74 (95% confidence interval 1.37 to 5.75) and “12–18 years” (2.68, 1.41 to 5.4); and a history of allergic diseases (1.67, 1.04 to 2.67).Interpretation A quarter of children experienced persistent symptoms months after hospitalization with acute covid-19 infection, with almost one in ten experiencing multi-system involvement. Older age and allergic diseases were associated with higher risk of persistent symptoms at follow-up.

Journal article

Munblit D, Nekliudov NA, Bugaeva P, Blyuss O, Timashev P, Warner JO, Comberiati P, Apfelbacher C, Politov ME, Yavorovskiy A, Avdeev S, Kapustina VA, Fomin V, Svistunov AA, Butnaru D, Glybochko Pet al., 2021, Reply to Russo et al., Clinical Infectious Diseases, Vol: 72, Pages: e1159-e1160, ISSN: 1058-4838

Journal article

Zepeda-Ortega B, Goh A, Xepapadaki P, Sprikkelman A, Nicolaou N, Hernandez REH, Latiff AHA, Yat MT, Diab M, Hussaini BA, Setiabudiawan B, Kudla U, van Neerven RJJ, Muhardi L, Warner JOet al., 2021, Strategies and future opportunities for the prevention, diagnosis, and management of cow milk allergy, Frontiers in Immunology, Vol: 12, ISSN: 1664-3224

The prevalence of food allergy has increased over the last 20-30 years, including cow milk allergy (CMA) which is one of the most common causes of infant food allergy. International allergy experts met in 2019 to discuss broad topics in allergy prevention and management of CMA including current challenges and future opportunities. The highlights of the meeting combined with recently published developments are presented here. Primary prevention of CMA should start from pre-pregnancy with a focus on a healthy lifestyle and food diversity to ensure adequate transfer of inhibitory IgG- allergen immune complexes across the placenta especially in mothers with a history of allergic diseases and planned c-section delivery. For non-breastfed infants, there is controversy about the preventive role of partially hydrolyzed formulae (pHF) despite some evidence of health economic benefits among those with a family history of allergy. Clinical management of CMA consists of secondary prevention with a focus on the development of early oral tolerance. The use of extensive Hydrolysate Formulae (eHF) is the nutrition of choice for the majority of non-breastfed infants with CMA; potentially with pre-, probiotics and LCPUFA to support early oral tolerance induction. Future opportunities are, among others, pre- and probiotics supplementation for mothers and high-risk infants for the primary prevention of CMA. A controlled prospective study implementing a step-down milk formulae ladder with various degrees of hydrolysate is proposed for food challenges and early development of oral tolerance. This provides a more precise gradation of milk protein exposure than those currently recommended.

Journal article

Munblit D, Simpson F, Mabbitt J, Dunn-Galvin A, Semple C, Warner JOet al., 2021, Legacy of COVID-19 infection in children: long-COVID will have a lifelong health/economic impact., Arch Dis Child

Journal article

Chauhan AJ, Brown TP, Storrar W, Bjermer L, Eriksson G, Radner F, Peterson S, Warner JOet al., 2021, Effect of nocturnal Temperature-controlled Laminar Airflow on the reduction of severe exacerbations in patients with severe allergic asthma: a meta-analysis, European Clinical Respiratory Journal, Vol: 8, Pages: 1-9, ISSN: 2001-8525

Background: Allergen avoidance is important in allergic asthma management. Nocturnal treatment with Temperature-controlled Laminar Airflow (TLA) has been shown to provide a significant reduction in the exposure to allergens in the breathing zone, leading to a long-term reduction in airway inflammation and improvement in Quality of life (QoL). Allergic asthma patients symptomatic on Global Initiative for Asthma (GINA) step 4/5 were found to benefit the most as measured by Asthma Quality of Life Questionnaire (AQLQ). However, the effect of TLA on severe asthma exacerbations is uncertain and therefore a meta-analysis was performed.Methods: Patients with severe allergic asthma (GINA 4/5) were extracted from two 1-year randomised, double-blind, placebo-controlled trials conducted with TLA. A meta-analysis of the effect on severe exacerbations was performed by negative binomial regression in a sequential manner, defined by baseline markers of asthma control (symptoms and QoL scores).Results: The pooled dataset included 364patients. Patients with more symptoms at baseline (ACT<18 or ACQ7>3; N=179), had a significant mean 41% reduction in severe exacerbations (RR=0.59 (0.38-0.90); p=0.015) in favour of TLA. Higher ACQ7 cut-points of 3.5-4.5 resulted in significant reductions of 48-59%.More uncontrolled patients based on AQLQ total and symptom domains ≤3.0 at baseline also showed a significant reduction in severe exacerbations for TLA vs. placebo ((47% (p=0.037) and 53% (p=0.011), respectively). The meta-analysis also confirmed a significant difference in AQLQ-responders ((Minimal Clinically Important Difference)≥0.5; 74% vs. 43%, p=0.04).Conclusion: This meta-analysis of individual patient data shows a beneficial effect on severe exacerbations and quality of life for TLA over placebo in more symptomatic patients with severe allergic asthma. These outcomes support the national management recommendations for patients with symptomatic severe allergic asthma. The ac

Journal article

Munblit D, Bobkova P, Spiridonova E, Shikhaleva A, Gamirova A, Blyuss O, Nekliudov N, Bugaeva P, Andreeva M, DunnGalvin A, Comberiati P, Apfelbacher C, Genuneit J, Avdeev S, Kapustina V, Guekht A, Fomin V, Svistunov AA, Timashev P, Drake TM, Hanson SW, Merson L, Horby P, Sigfrid L, Scott JT, Semple MG, Warner JO, Vos T, Olliaro P, Glybochko P, Butnaru Det al., 2021, Risk factors for long-term consequences of COVID-19 in hospitalised adults in Moscow using the ISARIC Global follow-up protocol: StopCOVID cohort study

<jats:title>ABSTRACT</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>The long-term sequalae of COVID-19 remain poorly characterised. In this study, we aimed to assess long-standing symptoms (LS) (symptoms lasting from the time of discharge) in previously hospitalised patients with COVID-19 and assess associated risk factors.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>This is a longitudinal cohort study of adults (≥18 years of age) with clinically diagnosed or laboratory-confirmed COVID-19 admitted to Sechenov University Hospital Network in Moscow, Russia. Data were collected from patients discharged between April 8 and July 10, 2020. Participants were interviewed via telephone using Tier 1 ISARIC Long-term Follow-up Study CRF and the WHO CRF for Post COVID conditions. Reported symptoms were further categorised based on the system(s) involved. Additional information on dyspnoea, quality of life and fatigue was collected using validated instruments. Multivariable logistic regressions were performed to investigate risk factors for development of LS categories.</jats:p></jats:sec><jats:sec><jats:title>Findings</jats:title><jats:p>Overall, 2,649 of 4,755 patients discharged from the hospitals were available for the follow-up and included in the study. The median age of the patients was 56 years (IQR, 46–66) and 1,353 (51.1%) were women. The median follow-up time since hospital discharge was 217.5 (200.4-235.5) days. At the time of the follow-up interview 1247 (47.1%) participants reported LS. Fatigue (21.2%, 551/2599), shortness of breath (14.5%, 378/2614) and forgetfulness (9.1%, 237/2597) were the most common LS reported. Chronic fatigue (25%, 658/2593) and respiratory (17.2% 451/2616) were the most common LS categories. with reporting of multi-system involvement (MSI) less common (11.3%; 299). Female sex was as

Journal article

Warner JO, Green RJ, Mustafa F, 2020, Allergy prevention – Reality or not?, Current Allergy and Clinical Immunology, Vol: 33, Pages: 130-137, ISSN: 1609-3607

While the epidemic of respiratory allergy (asthma and rhinitis) which began 50-60 years ago has begun to taper off in some parts of the world, most notably in affluent countries, a second wave involving food allergy and atopic dermatitis is in full swing. Once established allergic diseases, while episodic with changing manifestations over time, last for decades and are often lifelong. The number of lives affected and the quality of life implications mandates investigation of interventions to mitigate these conditions which together constitute the commonest long-term disorders to affect young people. The health economic burden of allergic diseases is considerable and as new biological therapies are approved this will only increase. The search for a cure has hitherto been fruitless but there is the hope that by understanding basic mechanisms it will eventually be possible to design targeted biological therapies to switch off the allergic process. However, this is an expensive enterprise and the costs of curative treatment may well be prohibitive. Prevention has become a focus for many long-term conditions and allergic disease must be included given the potential that strategies will confer considerable health/economic benefits. Health promotion which emphasises avoidance of environmental tobacco smoke, alcohol, pollution and obesity with promotion of exercise, and a nutritious diet has implications for allergic disease as well as the usual focus on cardio-vascular disease, cancer and metabolic syndrome. There are four potential &#39;windows of opportunity&#39; in early life which impact on the genetic potential to develop allergy in young children. They are in line with the developmental origins of health and disease hypothesis often now known as the ifrst 1 000 days from conception to the second birthday. Published studies of factors influencing the ontogeny and prevention of allergy have shown very different outcomes which makes careful attention to design a

Journal article

Renedo A, Miles S, Chakravorty S, Leigh A, Warner JO, Marston Cet al., 2020, Understanding the health-care experiences of people with sickle cell disorder transitioning from paediatric to adult services: This Sickle Cell Life, a longitudinal qualitative study, Health Services and Delivery Research, Vol: 8, Pages: 1-118, ISSN: 2050-4349

BackgroundTransitions from paediatric to adult health-care services cause problems worldwide, particularly for young people with long-term conditions. Sickle cell disorder brings particular challenges needing urgent action.ObjectivesUnderstand health-care transitions of young people with sickle cell disorder and how these interact with broader transitions to adulthood to improve services and support.MethodsWe used a longitudinal design in two English cities. Data collection included 80 qualitative interviews with young people (aged 13–21 years) with sickle cell disorder. We conducted 27 one-off interviews and 53 repeat interviews (i.e. interviews conducted two or three times over 18 months) with 48 participants (30 females and 18 males). We additionally interviewed 10 sickle cell disease specialist health-care providers. We used an inductive approach to analysis and co-produced the study with patients and carers.ResultsKey challenges relate to young people’s voices being ignored. Participants reported that their knowledge of sickle cell disorder and their own needs are disregarded in hospital settings, in school and by peers. Outside specialist services, health-care staff refuse to recognise patient expertise, reducing patients’ say in decisions about their own care, particularly during unplanned care in accident and emergency departments and on general hospital wards. Participants told us that in transitioning to adult care they came to realise that sickle cell disorder is poorly understood by non-specialist health-care providers. As a result, participants said that they lack trust in staff’s ability to treat them correctly and that they try to avoid hospital. Participants reported that they try to manage painful episodes at home, knowing that this is risky. Participants described engaging in social silencing (i.e. reluctance to talk about and disclose their condition for fear that others will not listen or will not understand) outside hospi

Journal article

Boyle R, Brown N, Chiang WC, Chien CM, Gold M, Hourihane J, Peake J, Quinn P, Rao R, Smith P, Tang M, Ziegler J, Warner Jet al., 2020, Partially hydrolysed, prebiotic supplemented whey formula for the prevention of allergic manifestations in high risk infants: a multicentre double-blind randomised controlled trial (Retraction of Vol 5, art no P30, 2015), Clinical and Translational Allergy, Vol: 10, ISSN: 2045-7022

Journal article

Munblit D, Warner J, Tudor-Williams G, Petrou L, Cheung KYet al., 2020, Excessive media consumption about COVID-19 is associated with increased state anxiety: Outcomes of a large online survey in Russia, Journal of Medical Internet Research, Vol: 22, Pages: 1-18, ISSN: 1438-8871

Background: The coronavirus disease 2019 (COVID-19) pandemic has potentially had a negative impact on the mental health and well being of individuals and families. Anxiety levels and risk factors within particular populations are poorly described.Objectives: To evaluate confidence, understanding, trust and concerns and levels of anxiety during COVID-19 pandemic in general population and assess risk factors for increased anxiety.Methods: We launched a cross-sectional online survey a large Russian population between 6th and 15th April 2020 using multiple social media platforms. A set of questions targeted confidence, understanding, trust and concerns in respondents. State-Trait Anxiety Inventory (STAI) was used to measure anxiety. Multiple linear regressions were used to model predictors of COVID-19 related anxiety.Results: The survey was completed by 23,756 out of 53,966 unique visitors (44.0% response rate); 21,364 of who were residing in 62 areas of Russia. State anxiety (S-Anxiety) scores were higher than Trait anxiety (T-Anxiety) across all regions of Russia (median S-Anxiety score 52 [IQR 44-60]), exceeding published norms. Time spent following news on COVID-19 was strongly associated with an increased S-Anxiety adjusted for baseline anxiety level. One to two hours spent reading COVID news was associated with 5.46 (95%CI 5.03-5.90) point difference, 2-3 hours 7.06 (6.37-7.74) and more than three hours 8.65 (7.82-9.47), respectively; all compared to less than 30 minutes per day. Job loss during pandemic was another important factor associated with higher S-Anxiety scores (3.95 [3.31 – 4.58]).Despite survey respondents reporting high confidence in information regarding COVID-19, as well as understanding of healthcare guidance, they reported low overall trust in state and local authorities and perception of country readiness.Conclusions: Among Russian respondents from multiple social media platforms, there is evidence of higher levels of state-anxiety asso

Journal article

Warner JO, 2020, Asthma/Rhinitis (The United Airway) and allergy: chicken or egg; which comes first?, Journal of Clinical Medicine, Vol: 9, Pages: 1-11, ISSN: 2077-0383

While allergy, asthma and rhinitis do not inevitably co-exist, there are strong associations. Not all those with asthma are allergic, rhinitis may exist without asthma, and allergy commonly exists in the absence of asthma and/or rhinitis. This is likely due to the separate gene/environment interactions which influence susceptibility to allergic sensitization and allergic airway diseases. Allergic sensitization, particularly to foods, and eczema commonly manifest early in infancy, and not infrequently are followed by the development of allergic rhinitis and ultimately asthma. This has become known as the "allergic march". However, many infants with eczema never develop asthma or rhinitis, and both the latter conditions can evolve without prior eczema or food allergy. Understanding the mechanisms underlying the ontogeny of allergic sensitization and allergic disease will facilitate rational approaches to the prevention and management of asthma and allergic rhinitis. Furthermore, a range of new, so-called biological, therapeutic approaches, targeting specific allergy-promoting and pro-inflammatory molecules, are now in clinical trials or have been recently approved for use by regulatory authorities and could have a major impact on disease prevention and control in the future. Understanding basic mechanisms will be essential to the employment of such medications. This review will explain the concept of the united airway (rhinitis/asthma) and associations with allergy. It will incorporate understanding of the role of genes and environment in relation to the distinct but interacting origins of allergy and rhinitis/asthma. Understanding the patho-physiological differences and varying therapeutic requirements in patients with asthma, with or without rhinitis, and with or without associated allergy, will aid the planning of a personalized evidence-based management strategy.

Journal article

Jarrold K, Helfer B, Eskander M, Crawley H, Trabulsi J, Caulfield LE, Duffy G, Garcia-Larsen V, Hayward D, Hyde M, Jeffries S, Knip M, Leonardi-Bee J, Loder E, Lodge CJ, Lowe AJ, McGuire W, Osborn D, Przyrembel H, Renfrew MJ, Trumbo P, Warner J, Schneeman B, Boyle RJet al., 2020, Guidance for the conduct and reporting of clinical trials of breast milk substitutes., JAMA Pediatrics, ISSN: 2168-6203

Importance: Breast milk substitutes (BMS) are important nutritional products evaluated in clinical trials. Concerns have been raised about the risk of bias in BMS trials, the reliability of claims that arise from such trials, and the potential for BMS trials to undermine breastfeeding in trial participants. Existing clinical trial guidance does not fully address issues specific to BMS trials. Objectives: To establish new methodological criteria to guide the design, conduct, analysis, and reporting of BMS trials and to support clinical trialists designing and undertaking BMS trials, editors and peer reviewers assessing trial reports for publication, and regulators evaluating the safety, nutritional adequacy, and efficacy of BMS products. Design, Setting, and Participants: A modified Delphi method was conducted, involving 3 rounds of anonymous questionnaires and a face-to-face consensus meeting between January 1 and October 24, 2018. Participants were 23 experts in BMS trials, BMS regulation, trial methods, breastfeeding support, infant feeding research, and medical publishing, and were affiliated with institutions across Europe, North America, and Australasia. Guidance development was supported by an industry consultation, analysis of methodological issues in a sample of published BMS trials, and consultations with BMS trial participants and a research ethics committee. Results: An initial 73 criteria, derived from the literature, were sent to the experts. The final consensus guidance contains 54 essential criteria and 4 recommended criteria. An 18-point checklist summarizes the criteria that are specific to BMS trials. Key themes emphasized in the guidance are research integrity and transparency of reporting, supporting breastfeeding in trial participants, accurate description of trial interventions, and use of valid and meaningful outcome measures. Conclusions and Relevance: Implementation of this guidance should enhance the quality and validity of BMS trials, prot

Journal article

Jarrold K, Helfer B, Eskander M, Crawley H, Trabulsi J, Caulfield LE, Duffy G, Garcia-Larsen V, Hayward D, Hyde M, Jeffries S, Knip M, Leonardi-Bee J, Loder E, Lodge CJ, Lowe AJ, McGuire W, Osborn D, Przyrembel H, Renfrew MJ, Trumbo P, Warner J, Schneeman B, Boyle Ret al., 2019, Guidance for the conduct and reporting of clinical trials of breastmilk substitutes: a Delphi consensus statement, JAMA Pediatrics, ISSN: 2168-6203

Importance: Breastmilk substitutes (BMS) are important nutritional products evaluated in clinical trials. Concerns have been raised about the risk of bias in BMS trials, the reliability of claims which arise from such trials, and the potential for BMS trials to undermine breastfeeding in trial participants. Existing clinical trial guidance68 does not fully address issues specific to BMS trials. Objective: To establish new methodological criteria to guide the design, conduct, analysis and reporting of BMS trials. To support clinical trialists designing and undertaking BMS trials, editors and peer reviewers assessing trial reports for publication, and regulators evaluating the safety, nutritional adequacy and efficacy of BMS products. Design, Setting, and Participants A modified Delphi method involving 3 rounds of anonymous questionnaires and a face-to-face consensus meeting between January and October 2018. Participants were 23 experts in BMS trials, BMS regulation, trial methodology, breastfeeding support, infant feeding research and medical publishing, affiliated with institutions across Europe, North America and Australasia. Guidance development was supported by an industry consultation, analysis of methodological issues in a sample of published BMS trials, and consultations with BMS trial 81 participants and a research ethics committee. Results: An initial 73 criteria, derived from the literature, were sent to the experts. The final consensus guidance contains a total of 54 essential and 4 recommended criteria. An 18-point checklist summarizes those criteria which are specific to BMS 5 trials. Key themes emphasised in the guidance are research integrity and transparency of reporting, supporting breastfeeding in trial participants, accurate description of trial interventions and use of valid and meaningful outcome measures. Conclusions and Relevance: Implementation of this guidance should enhance the quality and validity of BMS trials, protect BMS trial particip

Journal article

Renedo A, Miles S, Chakravorty S, Leigh A, Telfer P, Warner JO, Marston Cet al., 2019, Not being heard: barriers to high quality unplanned hospital care during young people's transition to adult services - evidence from 'this sickle cell life' research, BMC Health Services Research, Vol: 19, ISSN: 1472-6963

BACKGROUND: Young people's experiences of healthcare as they move into adult services can have a major impact on their health, and the transition period for young people with sickle cell disease (SCD) needs improvement. In this study, we explore how young people with SCD experience healthcare during this period of transition. METHODS: We conducted a co-produced longitudinal qualitative study, including 80 interviews in 2016-2017 with young people with SCD aged 13-21 (mean age 16.6) across two cities in England. We recruited 48 participants (30 female, 18 male): 27 interviews were one-off, and 53 were repeated 2-3 times over approximately 18 months. We used an inductive analytical approach, combining elements of Grounded Theory and thematic analysis. RESULTS: Participants reported significant problems with the care they received in A&E during painful episodes, and in hospital wards as inpatients during unplanned healthcare. They experienced delays in being given pain relief and their basic care needs were not always met. Participants said that non-specialist healthcare staff did not seem to know enough about SCD and when they tried to work with staff to improve care, staff often seemed not prepared to listen to them or act on what they said. Participants said they felt out of place in adult wards and uncomfortable with the differences in adult compared with paediatric wards. Because of their experiences, they tried to avoid being admitted to hospital, attempting to manage their painful episodes at home and accessing unplanned hospital care only as a last resort. By contrast, they did not report having problems within SCD specialist services during planned, routine care. CONCLUSIONS: Our study underscores the need for improvements to make services youth-friendly and youth-responsive, including training staff in SCD-specific care, compassionate care and communication skills that will help them elicit and act on young people's voices to ensure they are involv

Journal article

Blyuss O, Cheung KY, Chen J, Parr C, Petrou L, Komarova A, Kokina M, Luzan P, Pasko E, Eremeeva A, Peshko D, Eliseev VI, Pedersen SA, Azad MB, Jarvinen KM, Peroni DG, Verhasselt V, Boyle RJ, Warner JO, Simpson MR, Munblit Det al., 2019, Statistical approaches in the studies assessing associations between human milk immune composition and allergic diseases: A scoping review, Nutrients, Vol: 11, Pages: 1-15, ISSN: 2072-6643

A growing number of studies are focusing on the associations between human milk (HM) immunological composition and allergic diseases. This scoping review aims to identify statistical methods applied in the field and highlight pitfalls and unmet needs. A comprehensive literature search in MEDLINE and Embase retrieved 13,607 unique records. Following title/abstract screening, 29 studies met the selection criteria and were included in this review. We found that definitions of colostrum and mature milk varied across the studies. A total of 17 out of 29 (59%) studies collected samples longitudinally, but only 12% of these used serial (longitudinal) analyses. Multivariable analysis was used in 45% of the studies, but statistical approaches to modelling varied largely across the studies. Types of variables included as potential confounding factors differed considerably between models. Discrimination analysis was absent from all studies and only a single study reported classification measures. Outcomes of this scoping review highlight lack of standardization, both in data collection and handling, which remains one of the main challenges in the field. Improved standardization could be obtained by a consensus group of researchers and clinicians that could recommend appropriate methods to be applied in future prospective studies, as well as already existing datasets.

Journal article

Khaleva E, Gridneva Z, Geddes DT, Oddy WH, Colicino S, Blyuss O, Boyle R, Warner J, Munblit Det al., 2019, Transforming growth factor beta in human milk and allergic outcomes in children: A systematic review, Clinical and Experimental Allergy, Vol: 49, Pages: 1201-1213, ISSN: 0954-7894

BACKGROUND: Human milk (HM) transforming growth factor beta (TGF-β) is critical for inflammation regulation and oral tolerance promotion. Previous reports suggested that variations in HM TGF-β levels are associated with allergic outcomes. OBJECTIVE: We undertook a systematic review (PROSPERO 2017 CRD42017069920) to reassess the evidence on the relationships between HM TGF-β and allergic outcomes in children. METHODS: Electronic bibliographic databases (MEDLINE, EMBASE, Cochrane Library) were systematically searched. Two independent reviewers screened reference lists, extracted the data and assessed risk of bias using the National Institute for Clinical Excellence methodological checklist. RESULTS: A total of 21 studies were identified. Sixteen studies assessed relationships between HM TGF-β and risk of eczema; 14, allergic sensitisation; 9, wheezing/asthma; 6, food allergy; 3, allergic rhinitis/conjunctivitis. Five cohorts (5/18, 28%) reported a protective effect of TGF-β1, while 3 (3/10, 30%) suggested increased risk of allergic outcomes development and 1 (1/10, 10%), a protective effect of TGF-β2 on eczema. Meta-analysis was not possible due to significant heterogeneity in methodology, age of outcome assessment and differing statistical approaches. 71% (15/21) of studies carried a high risk of bias. CONCLUSION AND CLINICAL RELEVANCE: In contrast with previous findings we did not find strong evidence of associations between HM TGF-β and allergic outcomes. Differences in studies' methodology and outcomes do not allow unconditional rejection or acceptance of the hypothesis that HM TGF-β influences the risk of allergy development. Future studies on diverse populations employing standardised methods, accurate phenotyping of outcomes and evaluation of the effect of TGF-β in combination with other HM immune markers, microbiome and oligosaccharides are required.

Journal article

Boix-Amorós A, Collado MC, Van't Land B, Calvert A, Le Doare K, Garssen J, Hanna H, Khaleva E, Peroni DG, Geddes DT, Kozyrskyj AL, Warner JO, Munblit Det al., 2019, Reviewing the evidence on breast milk composition and immunological outcomes., Nutr Rev

A large number of biologically active components have been found in human milk (HM), and in both human and animal models, studies have provided some evidence suggesting that HM composition can be altered by maternal exposures, subsequently influencing health outcomes for the breastfed child. Evidence varies from the research studies on whether breastfeeding protects the offspring from noncommunicable diseases, including those associated with immunological dysfunction. It has been hypothesized that the conflicting evidence results from HM composition variations, which contain many immune active molecules, oligosaccharides, lactoferrin, and lysozyme in differing concentrations, along with a diverse microbiome. Determining the components that influence infant health outcomes in terms of both short- and long-term sequelae is complicated by a lack of understanding of the environmental factors that modify HM constituents and thereby offspring outcomes. Variations in HM immune and microbial composition (and the differing infantile responses) may in part explain the controversies that are evidenced in studies that aim to evaluate the prevalence of allergy by prolonged and exclusive breastfeeding. HM is a "mixture" of immune active factors, oligosaccharides, and microbes, which all may influence early immunological outcomes. This comprehensive review provides an in-depth overview of existing evidence on the studied relationships between maternal exposures, HM composition, vaccine responses, and immunological outcomes.

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Levy ML, Fleming L, Warner JO, Bush Aet al., 2019, Paediatric asthma care in the UK: fragmented and fatally fallible., British Journal of General Practice, Vol: 69, Pages: 405-406, ISSN: 0960-1643

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Munblit D, Verhasselt V, Warner JO, 2019, Editorial: human milk composition and health outcomes in children, Frontiers in Pediatrics, Vol: 7, Pages: 1-3, ISSN: 2296-2360

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Dunning J, Blankley S, Hoang LT, Cox M, Graham CM, James PL, Bloom CI, Chaussabel D, Banchereau J, Brett SJ, MOSAIC Investigators, Moffatt MF, O'Garra A, Openshaw PJMet al., 2019, Author Correction: Progression of whole-blood transcriptional signatures from interferon-induced to neutrophil-associated patterns in severe influenza., Nature Immunology, Vol: 20, Pages: 373-373, ISSN: 1529-2908

In the version of this article initially published, a source of funding was not included in the Acknowledgements section. That section should include the following: P.J.M.O. was supported by EU FP7 PREPARE project 602525. The error has been corrected in the HTML and PDF version of the article.

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Bjermer L, Eriksson G, Radner F, Peterson S, Warner JOet al., 2019, Time to onset of improvements in Quality of Life from Temperature-controlled Laminar Airflow (TLA) in severe allergic asthma, Respiratory Medicine, Vol: 147, Pages: 19-25, ISSN: 0954-6111

BackgroundAllergen avoidance is important in allergic asthma management. Nocturnal treatment with Temperature-controlled Laminar Airflow (TLA; Airsonett®) has been shown to provide significant reduction of exposure to allergens in the breathing zone, leading to long-term reduction in airway inflammation and improvement in quality of life. Allergic asthma patients uncontrolled on GINA step 4 were found to benefit the most. A frequently asked question from clinicians and funders is related to time to onset (TTO) of improvements for patients using TLA.MethodsAsthma Quality of Life Questionnaire (AQLQ) scores were collected in a previous study. TTO of improvements in Quality of Life was analysed for difference (TLA-placebo) in Area-under-Curve using backwards deletion from 12, 9, 6, 3 down to 1 month for the AQLQ total score, the four individual domains and specifically the sleep question.ResultsPatients with uncontrolled asthma on GINA step 4 (n = 87)) reported a statistically significant and clinically relevant (≥0.5 point) improvement in total AQLQ score (0.57; p = 0.009) after 3 months treatment for TLA over placebo. The shortest TTO was within 1 month for the environmental domain (0.68; p = 0.016) and the sleep question (0.771; p = 0.037). TTO for the emotional and symptom domains was 3 months (0.66; p = 0.020 and 0.64; p = 0.014 respectively) and for the activity domain 6 months (0.47; p = 0.036).ConclusionNocturnal avoidance of allergens using TLA provided a statistically significant and clinically relevant improvement in total AQLQ score within 3 months in patients in the GINA 4 + ACT<18 group. Questions related to sleep quality may provide the first signal of response already within a month after commencing treatment.

Journal article

Chakravorty S, Tallett A, Sathyamoorthy G, Witwicki C, Hay H, Ogundipe A, Mkandawire C, Ojeer P, Whitaker A, Thompson J, Warner JOet al., 2018, Patient reported experience measure in Sickle Cell disease, Archives of Disease in Childhood, Vol: 103, Pages: 1104-1109, ISSN: 1468-2044

Objectives:To develop Patient Reported Experience Measure surveys for patients with Sickle CellDisease (SCD) to understand their healthcare and lived experience in the UK and fortheir use in future to inform healthcare service development.Design:Picker methodology was used as follows:1. Qualitative scoping by focus group discussions2. Questionnaire development through stakeholder consultations3. Construct validation of questionnaires through cognitive testing4. Further assessment of construct validity by a nationwide pilot surveySetting:Patients with SCD and their carers were eligible. Focus group discussions took place innon-hospital settings, arranged out-of-hours. Cognitive testing took place in specialistSickle Cell clinics. The pilot survey was available to UK participants only and wasadministered through web-based questionnaires, face-to face completion and in sicklecell community events.Participants:Thirty-three patients and carers took part in the focus groups, 21 participants undertookcognitive testing and 722 respondents completed the pilot survey.Results:Findings highlighted a widespread prevalence of poor knowledge about SCD amonghealthcare providers and the public. Poorer experience of care was present in the emergency setting compared to planned care, of which lack of timely provision of painrelief was of concern. Adolescents and young people reported significantly poorerexperience of care in several domains compared to children or adults.Conclusions:The new surveys functioned well, with good evidence of validity, and were accessible tothe SCD patient population, supporting their future use in assessing patient experienceto inform service delivery and improvements in care quality.

Journal article

Munblit D, Abrol P, Sheth S, Chow L, Khaleva E, Asmanov A, Lauriola S, Padovani EM, Comberiati P, Boner AL, Warner JO, Boyle RJ, Peroni DGet al., 2018, Levels of growth factors and IgA in colostrum of women from Burundi and Italy, Nutrients, Vol: 10, ISSN: 2072-6643

Colostrum is produced in the first days postpartum. It is a known source of immune mediators for a newborn within the first week of life. Although it is still unclear if colostrum composition varies between populations, recent data suggest differences. Hepatocyte growth factor (HGF); transforming growth factor-β (TGF-β) 1, 2, and 3; and immunoglobulin A (IgA) are key immunological components of colostrum that stimulate neonatal gastrointestinal and immune system development. We aimed to investigate the differences in the concentration between immune markers in the colostrum of mothers living in Burundi and Italy, and to identify the factors associated with differences. In this cross-sectional birth cohort study, a total of 99 colostrum samples from Burundian (n = 23) and Italian (n = 76) women were collected at 0 to 6 days postpartum. A clinical chemistry analyser was used for IgA quantification and electro-chemiluminescence, for HGF and TGFβ1-3 assessment. A univariate analysis and multivariate linear regression model were used for statistical testing. The concentrations of TGF-β2 (p = 0.01) and IgA (p < 0.01) were significantly higher in the colostrum from the women residing in Burundi than in Italy, both in a univariate analysis and upon the adjustment for confounding factors. A similar trend is seen for HGF, reaching statistical significance upon a multivariate analysis. We found a moderate to strong positive correlation between the TGF-β isoforms and IgA concentration in both countries (p < 0.01), with stronger concentration in the colostrum from Burundi. The results of this study are in support of previous data, suggesting that concentration of the immune active molecules is higher in the human milk of women residing in developing countries. However, with a small sample size, caution must be applied, as the findings require further confirmation. Future work should also be focused on other factors (e.g., lipid and microbial compos

Journal article

Khaleva E, Gridneva Z, Geddes D, Oddy WH, Boyle R, Warner J, Munblit Det al., 2018, TGF-beta in human milk and allergic outcomes in children: A systematic review, ALLERGY, Vol: 73, Pages: 682-683, ISSN: 0105-4538

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Mavroudi A, Chrysochoou E-A, Boyle RJ, Trypsianis G, Xinias I, Cassimos D, Imvrios G, Katotomichelakis M, Karagiannidou A, Karantaglis N, Kourentas G, Warner JOet al., 2018, Validation of the children's sleep habits questionnaire in a sample of Greek children with allergic rhinitis, Allergologia et Immunopathologia, Vol: 46, Pages: 389-393, ISSN: 0301-0546

BACKGROUND: Obstructive respiratory disorders, such as allergic rhinitis and asthma may impair sleep quality. The aim of this study is to validate the Children's Sleep Habits Questionnaire (CSHQ) for Greek children from 6 to 14 years of age. No validated tool has been developed so far to assess sleep disturbances in Greek school-aged children. METHODS: We examined the reliability and validity of the CSHQ in a sample of children with allergic rhinitis (AR) and a non-clinical population of parents of these children as a proxy measure of children's AR quality of life (QoL) as evaluated by the Pediatric Allergic Rhinitis Quality of Life (PedARQoL) questionnaire. RESULTS: The CSHQ questionnaire Child's Form (CF) had a moderate internal consistency with a Cronbach's alpha 0.671 and Guttman split-half coefficient of 0.563 when correlated with the PedARQoL (CF). There was also a moderate intraclass correlation of ICC=0.505 between the responses to both questionnaires in the two visits. The CSHQ Parent's Form (PF) had a very good internal consistency with a Cronbach's alpha of 0.928 and Guttman split-half coefficient of 0.798. There was a high intraclass correlation of 0.643 between the responses in the two visits. CONCLUSIONS: The Greek version of the CSHQ CF, but particularly the PF has proved to be a very reliable clinical instrument, which can be used in clinical trials for assessing sleep quality in school-aged children with sleep disturbances because of obstructive airway disorders, such as AR.

Journal article

Ulfman LH, Leusen JHW, Savelkoul HFJ, Warner JO, van Neerven RJJet al., 2018, Effects of bovine immunoglobulins on immune function, allergy, and infection, Frontiers in Nutrition, Vol: 5, ISSN: 2296-861X

This review aims to provide an in depth overview of the current knowledge of the effects of bovine immunoglobulins on the human immune system. The stability and functional effects of orally ingested bovine immunoglobulins in milk products are described and potential mechanisms of action are discussed. Orally ingested bovine IgG (bovine IgG) can be recovered from feces, ranging from very low levels up to 50% of the ingested IgG that has passed through the gastrointestinal tract. In infants the recovered levels are higher than in adults most likely due to differences in stomach and intestinal conditions such as pH. This indicates that bovine IgG can be functionally active throughout the gastrointestinal tract. Indeed, a large number of studies in infants and adults have shown that bovine IgG (or colostrum as a rich source thereof) can prevent gastrointestinal tract infections, upper respiratory tract infections, and LPS-induced inflammation. These studies vary considerably in target group, design, source of bovine IgG, dosage, and endpoints measured making it hard to draw general conclusions on effectiveness of bovine immunoglobulin rich preparations. Typical sources of bovine IgG used in human studies are serum-derived IgG, colostrum, colostrum-derived IgG, or milk-derived immunoglobulins. In addition, many studies have used IgG from vaccinated cows, but studies using IgG from nonimmunized animals have also been reported to be effective. Mechanistically, bovine IgG binds to many human pathogens and allergens, can neutralize experimental infection of human cells, and limits gastrointestinal inflammation. Furthermore, bovine IgG binds to human Fc receptors which, enhances phagocytosis, killing of bacteria and antigen presentation and bovine IgG supports gastrointestinal barrier function in in vitro models. These mechanisms are becoming more and more established and explain why bovine IgG can have immunological effects in vivo. The inclusion of oral bovine immunoglobuli

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