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Munblit D, Greenhawt M, Brough HA, et al., 2022, Allergic diseases and immunodeficiencies in children, lessons learnt from COVID-19 pandemic by 2022: A statement from the EAACI-section on pediatrics, PEDIATRIC ALLERGY AND IMMUNOLOGY, Vol: 33, ISSN: 0905-6157
Goh A, Muhardi L, Ali A, et al., 2022, Differences between peptide profiles of extensive hydrolysates and their influence on functionality for the management of cow's milk allergy: A short review, Frontiers in Allergy, Vol: 3, ISSN: 2673-6101
Extensively hydrolyzed formulas (eHFs) are recommended for the dietary management of cow's milk protein allergy (CMPA) in non-exclusively breastfed infants. Studies show that peptide profiles differ between eHFs. This short review aims to highlight the variability in peptides and their ability to influence allergenicity and possibly the induction of tolerance by different eHFs. The differences between eHFs are determined by the source of the protein fraction (casein or whey), peptide size-distribution profile and residual β-lactoglobulin which is the most immunogenic and allergenic protein in bovine milk for human infants as it is not present in human breastmilk. These differences occur from the hydrolyzation process which result in variable IgE reactivity against cow's milk allergen epitopes by subjects with CMPA and differences in the Th1, Th2 and pro-inflammatory cytokine responses elicited. They also have different effects on gut barrier integrity. Results suggest that one particular eHF-casein had the least allergenic potential due to its low residual allergenic epitope content and demonstrated the greatest effect on restoring gut barrier integrity by its effects on mucin 5AC, occludin and Zona Occludens-1 in human enterocytes. It also increased the production of the tolerogenic cytokines Il-10 and IFN-γ. In addition, recent studies documented promising effects of optional functional ingredients such as pre-, pro- and synbiotics on the management of cow's milk allergy and induction of tolerance, in part via the induction of the production of short chain fatty acids. This review highlights differences in the residual allergenicity, peptide size distribution, presence of optional functional ingredients and overall functionality of several well-characterized eHFs which can impact the management of CMPA and the ability to induce immune tolerance to cow's milk protein.
Warner JO, 2022, Autonomy vs beneficence: shared decision-making in allergy, Current Allergy and Clinical Immunology, Vol: 35, Pages: 138-142, ISSN: 1609-3607
Understanding the principles of ethical clinical practice is fundamental to making appropriate decisions. While ethical practice is a regulatory and legal obligation, it more importantly improves clinical judgement and the delivery of effective care. Traditionally, there are four principles: autonomy (giving choice to the patient); beneficence (paternalism); nonmaleficence (do no harm); and justice (confidentiality and equality). However, a fifth principle, fidelity, which constitutes fairness, truthfulness and advocacy, must be included. Balancing between autonomy and beneficence is like walking on a tight-rope, particularly when dealing with children and young people. However, competence to make sensible autonomous decisions is not linearly related to age. Adults sometimes make bad decisions and do not necessarily understand the long-term consequences of their actions. Nevertheless, whereas children are not, adults are legally considered to have autonomous rights. Irrespective of age, generating an accord between clinician and patient through empathetic consultation has the best chance of achieving favourable patient experience and consequent optimal clinical outcomes. In most situations honesty and full disclosure should be the rule; but, very occasionally, it may be necessary to modify approaches to avoid adverse consequences. The five principles are discussed and illustrated with case scenarios. It is not always possible to achieve consensus and sometimes there are no correct answers to ethical dilemmas. But discussion with colleagues, ethicists, patients and their representatives will improve ethical clinical practice.
Munblit D, Warner J, 2022, Prevalence and risk factors of post-COVID-19 condition in adults and children at 6 and 12 months after hospital discharge: a prospective, cohort study in Moscow (Stop COVID), BMC Medicine, Vol: 20, ISSN: 1741-7015
Background Previous studies assessing the prevalence of COVID-19 sequelae in adults and children were performed in the absence of an agreed definition. We investigated prevalence of post-COVID-19 condition (PCC) (WHO definition), at 6- and 12-months follow-up, among previously hospitalised adults and children and assessed risk factors.MethodsProspective cohort study of children and adults with confirmed COVID-19 in Moscow, hospitalised between April and August, 2020. Two follow-up telephone interviews, using the International Severe Acute Respiratory and Emerging Infection Consortium survey, were performed at 6 and 12 months after discharge.Results1013 of 2509 (40%) of adults and 360 of 849 (42%) of children discharged participated in both the 6- and 12-month follow-ups. PCC prevalence was 50% (95%CI 47 – 53) in adults and 20% (95%CI 16 - 24) in children at 6 months, with decline to 34% (95%CI 31 - 37) and 11% (95%CI 8 - 14), respectively, at 12 months. In adults, female sex was associated with PCC at 6- and 12-month follow-up (OR 2.04, 95% CI 1.57 to 2.65) and (OR 2.04, 1.54 to 2.69), respectively. Pre-existing hypertension (OR 1.42, 1.04 to 1.94) was associated with post-COVID-19 condition at 12 months. In children, neurological comorbidities were associated with PCC both at 6 months (OR 4.38, 1.36 to 15.67) and 12 months (OR 8.96, 2.55 to 34.82) while allergic respiratory diseases were associated at 12 months (OR 2.66, 1.04 to 6.47).ConclusionsAlthough prevalence of PCC declined one year after discharge, one in three adults and one in ten children experienced ongoing sequelae. In adults, females and persons with pre-existing hypertension, and in children, persons with neurological comorbidities or allergic respiratory diseases are at higher risk of PCC.
Munblit D, Nicholson T, Akrami A, et al., 2022, A core outcome set for post-COVID-19 condition in adults for use in clinical practice and research: an international Delphi consensus study, LANCET RESPIRATORY MEDICINE, Vol: 10, Pages: 715-724, ISSN: 2213-2600
Lythgoe M, Desai A, Gyawali B, et al., 2022, Cancer therapy approval timings, review speed and publication of pivotal registration trials in the US and Europe from 2010-2019, Jama Network Open, Vol: 5, ISSN: 2574-3805
Importance: Ensuring patients have access to safe and efficacious medicines in a timely manner is an essential goal for regulatory agencies, which has particular significance in oncology due to the significant unmet need for new therapies. The two largest regulatory agencies, the FDA and EMA have pivotal global roles, and their recommendations and approvals are frequently followed by other national regulators.Objective: To compare market authorization dates for new oncology therapies approved in the US and Europe over the past decade and to examine and contrast the regulatory activities of the FDA and EMA in the approval of new cancer medicines.Design, Setting and Participants: A review of the FDA and EMA regulatory databases to identify new oncology therapies approved in both the US and Europe from 2010 to 2019, and characterization of the timings of regulatory activities. Main Outcome Measures: Regulatory approval date, review time, submission of market authorization application, accelerated approval or conditional marketing authorisation status and proportion of approvals prior to peer-reviewed publication of pivotal trial results. Results: In total, 89 new concomitant oncology therapies were approved in the US and Europe from 2010 to 2019. The FDA approved 85 (95%) oncology therapies before European authorization and 4 (5%) therapies after. The median delay in market authorization for new oncology therapies in Europe was 241 days compared to the US. The median review time was 200 days and 426 days for the FDA and EMA, respectively. 60 (67%) new licensing applications were submitted to the FDA first, compared to 25 (28%) to the EMA. 35 (39%) oncology therapies were approved by the FDA prior to pivotal study publication, whereas only 8 (9%) by the EMA.Conclusion and Relevance: In this study we demonstrate that new oncology therapies are approved earlier in the US than Europe. The FDA receives licensing applications sooner and has shorter review times. However, mor
Gamirova A, Berbenyuk A, Levina D, et al., 2022, Food Proteins in Human Breast Milk and Probability of IgE-Mediated Allergic Reaction in Children During Breastfeeding: A Systematic Review, JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE, Vol: 10, Pages: 1312-+, ISSN: 2213-2198
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Warner JO, 2022, Translating results from research into clinical practice, ARCHIVES OF DISEASE IN CHILDHOOD, Vol: 107, Pages: 501-502, ISSN: 0003-9888
Warner JO, Warner JA, 2022, The foetal origins of allergy and potential nutritional interventions to prevent disease, Nutrients, Vol: 14, ISSN: 2072-6643
The first nine months from conception to birth involves greater changes than at any other time in life, affecting organogenesis, endocrine, metabolic and immune programming. It has led to the concept that the “first 1000 days” from conception to the second birthday are critical in establishing long term health or susceptibility to disease. Immune ontogeny is predominantly complete within that time and is influenced by the maternal genome, health, diet and environment pre-conception and during pregnancy and lactation. Components of the immunological protection of the pregnancy is the generation of Th-2 and T-regulatory cytokines with the consequence that neonatal adaptive responses are also biased towards Th-2 (allergy promoting) and T-regulatory (tolerance promoting) responses. Normally after birth Th-1 activity increases while Th-2 down-regulates and the evolving normal human microbiome likely plays a key role. This in turn will have been affected by maternal health, diet, exposure to antibiotics, mode of delivery, and breast or cow milk formula feeding. Complex gene/environment interactions affect outcomes. Many individual nutrients affect immune mechanisms and variations in levels have been associated with susceptibility to allergic disease. However, intervention trials employing single nutrient supplementation to prevent allergic disease have not achieved the expected outcomes suggested by observational studies. Investigation of overall dietary practices including fresh fruit and vegetables, fish, olive oil, lower meat intake and home cooked foods as seen in the Mediterranean and other healthy diets have been associated with reduced prevalence of allergic disease. This suggests that the “soup” of overall nutrition is more important than individual nutrients and requires further investigation both during pregnancy and after the infant has been weaned. Amongst all the potential factors affecting allergy outcomes, modification of maternal an
Munblit D, Simpson F, Mabbitt J, et al., 2022, Legacy of COVID-19 infection in children: long-COVID will have a lifelong health/economic impact, ARCHIVES OF DISEASE IN CHILDHOOD, Vol: 107, ISSN: 0003-9888
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- Citations: 3
Munblit D, Parr C, Chen J, et al., 2022, Studying the Post-COVID-19 condition: research challenges, strategies and importance of Core Outcome Set development, BMC Medicine, Vol: 20, Pages: 1-13, ISSN: 1741-7015
Background A substantial portion of people with COVID-19 subsequently experience lasting symptoms including fatigue, shortness of breath and neurological complaints such as cognitive dysfunction many months after acute infection. Emerging evidence suggests that this condition, commonly referred to as Long COVID but also known as Post-Acute Sequelae of SARS-CoV-2 infection (PASC) or post-COVID-19 condition, could become a significant global health burden. Main textWhile the number of studies investigating the post-COVID-19 condition is increasing, there is no agreement on how this new disease should be defined and diagnosed in clinical practice and what relevant outcomes to measure. There is an urgent need to optimise and standardise outcome measures for this important patient group both for clinical services and for research and to allow comparing and pooling of data. ConclusionsA Core Outcome Set for post-COVID-19 condition should be developed in the shortest time frame possible, for improvement in data quality, harmonisation, and comparability between different geographical locations. We call for a global initiative, involving all relevant partners, including, but not limited to, healthcare professionals, researchers, methodologists, patients, and caregivers. We urge coordinated actions aiming to develop a Core Outcome Set (COS) for post-COVID-19 condition in both the adult and paediatric populations.
Osmanov IM, Spiridonova E, Bobkova P, et al., 2022, Risk factors for long covid in previoulsy hospitalsied children using the ISARIC Global Follow-Up Protocol: a prospective cohort study, European Respiratory Journal, Vol: 59, 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.
Warner JO, Warner JA, Munblit D, 2022, Hypotheses to explain the associations between asthma and the consequences of COVID-19 infection., Clinical and Experimental Allergy, Vol: 52, Pages: 7-9, ISSN: 0954-7894
Barker S, Daniels L, Chang Y-S, et al., 2021, Allergy education and training for physicians., World Allergy Organ J, Vol: 14, Pages: 1-12, ISSN: 1939-4551
The increasing prevalence of allergic diseases has placed a significant burden on global healthcare and society as whole. This has necessitated a rapid development of "allergy" as a specialist area. However, as allergy is so common and, for most, relatively easy to diagnose and control, all clinicians need to have basic knowledge and competence to manage mild disease and recognize when referral is required. The allergology specialty has not yet been recognized in many countries and even where allergy is fully recognized as a specialty, the approach to training in allergy differs significantly. In the light of recent developments in allergy diagnosis and management, there is an urgent need to harmonize core competences for physicians, as well as the standardization of core principles for medical education and post-graduate training in allergy. All physicians and allied health professionals must appreciate the multidisciplinary team (MDT) approach to allergy, which is key to achieving the highest standards in holistic care. Due to worldwide variation in resources and personnel, some MDT roles will need to be absorbed by the treating physician or other healthcare professionals. We draw particular attention to the role of psychological input for all allergy patients, dietetic input in the case of food allergy and patient education to support all patients in the supported self-management of their condition on a daily basis. A strong appreciation of these multidisciplinary aspects will help physicians provide quality patient-centered care. We consider that harmonization of allergy components within undergraduate curricula is crucial to ensure all physicians develop the appropriate allergy-related knowledge and skills, particularly in light of inconsistencies seen in the primary care management of allergy. This review from the World Allergy Organization (WAO) Education and Training Committee also outlines allergy-related competences required
Daniels L, Barker S, Chang Y-S, et al., 2021, Harmonizing allergy care–integrated care pathways and multidisciplinary approaches, World Allergy Organization Journal, Vol: 14, ISSN: 1939-4551
There is a wide time gap between the publication of evidence and the application of new knowledge into routine clinical practice. The consequence is sub-optimal outcomes, particularly concerning for long-term relapsing/remitting conditions such as allergic diseases. In response, there has been a proliferation of published guidelines which systematically review evidence for the gold-standard management of most allergic disorders. However, this has not necessarily been followed by improved outcomes, partly due to a lack of coordination across the patient pathway. This has become known as the "second translational gap". A proposed solution is the development and implementation of integrated care pathways (ICPs) to optimize patient outcomes, with the notion that evidence-based medicine requires evidence-based implementation. ICP implementation is shown to improve short-term outcomes for acute conditions and routine surgery, including reduced length of hospital stay, improved documentation and improved patient safety. However, this improvement is not reflected in patient experience or patient-centered functional outcomes. The implementation of life-long, cost-effective interventions within comprehensive pathways requires a deep appreciation for complexity within allergy care.We promote an evidence-based methodology for the implementation of ICPs for allergic disorders in which all stakeholders in allergy care are positioned equally and encouraged to contribute, particularly patients and their caregivers. This evidence-based process commences with scoping the unmet needs, followed by stakeholder mapping. All stakeholders are invited to meetings to develop a common vision and mission through the generation of action/effect diagrams which helps build concordance across the agencies. Dividing the interventions into achievable steps and reviewing with plan/do/study/act cycles will gradually modify the pathway to achieve the best outcomes. While the management guidel
Munblit D, Bobkova P, Spiridonova E, et al., 2021, Incidence and risk factors for persistent symptoms in adults previously hospitalized for COVID-19, Clinical and Experimental Allergy, Vol: 51, Pages: 1107-1120, ISSN: 0954-7894
BackgroundThe long-term sequalae of COVID-19 remain poorly characterized. We assessed persistent symptoms in previously hospitalized patients with COVID-19 and assessed potential risk factors.MethodsData were collected from patients discharged from 4 hospitals in Moscow, Russia between 8 April and 10 July 2020. Participants were interviewed via telephone using an ISARIC Long-term Follow-up Study questionnaire.Results2,649 of 4755 (56%) discharged patients were successfully evaluated, at median 218 (IQR 200, 236) days post-discharge. COVID-19 diagnosis was clinical in 1291 and molecular in 1358. Most cases were mild, but 902 (34%) required supplemental oxygen and 68 (2.6%) needed ventilatory support. Median age was 56 years (IQR 46, 66) and 1,353 (51.1%) were women. Persistent symptoms were reported by 1247 (47.1%) participants, with fatigue (21.2%), shortness of breath (14.5%) and forgetfulness (9.1%) the most common symptoms and chronic fatigue (25%) and respiratory (17.2%) the most common symptom categories. Female sex was associated with any persistent symptom category OR 1.83 (95% CI 1.55 to 2.17) with association being strongest for dermatological (3.26, 2.36 to 4.57) symptoms. Asthma and chronic pulmonary disease were not associated with persistent symptoms overall, but asthma was associated with neurological (1.95, 1.25 to 2.98) and mood and behavioural changes (2.02, 1.24 to 3.18), and chronic pulmonary disease was associated with chronic fatigue (1.68, 1.21 to 2.32).ConclusionsAlmost half of adults admitted to hospital due to COVID-19 reported persistent symptoms 6 to 8 months after discharge. Fatigue and respiratory symptoms were most common, and female sex was associated with persistent symptoms.
Munblit D, Sigfrid L, Warner JO, 2021, Setting Priorities to Address Research Gaps in Long-term COVID-19 Outcomes in Children, JAMA PEDIATRICS, Vol: 175, Pages: 1095-1096, ISSN: 2168-6203
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Munblit D, Nekliudov NA, Bugaeva P, et 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.
Munblit D, Nekliudov NA, Bugaeva P, et al., 2021, Reply to Russo et al., Clinical Infectious Diseases, Vol: 72, Pages: e1159-e1160, ISSN: 1058-4838
Zepeda-Ortega B, Goh A, Xepapadaki P, et 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.
Chauhan AJ, Brown TP, Storrar W, et 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
Munblit D, Bobkova P, Spiridonova E, et 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
Osmanov IM, Spiridonova E, Bobkova P, et al., 2021, Risk factors for long covid in previously hospitalised children using the ISARIC Global follow-up protocol: A prospective cohort study
<jats:p>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 and younger) admitted with confirmed Covid-19 to Z.A. Bashlyaeva Children's Municipal Clinical Hospital in Moscow, Russia. Children admitted to the hospital during the first wave of the pandemic, 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 Overall, 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: 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. Our findings highlight the need for replication and further investigation of potential mechanisms as well as c
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 'windows of opportunity' 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
Renedo A, Miles S, Chakravorty S, et 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
Boyle R, Brown N, Chiang WC, et 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
Munblit D, Warner J, Tudor-Williams G, et 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
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.
Jarrold K, Helfer B, Eskander M, et 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
Jarrold K, Helfer B, Eskander M, et 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
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