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Seylanova N, Chernyavskaya A, Degtyareva N, et al., 2024, Core outcome measurement set for research and clinical practice in post COVID-19 condition (long COVID) in children and young people: an international Delphi consensus study "PC-COS Children", European Respiratory Journal, Vol: 63, ISSN: 0903-1936
The COVID-19 pandemic substantially impacted different age groups, with children and young people (CYP) not exempted. Many have experienced enduring health consequences. Presently, there is no consensus on the health outcomes to assess in CYP with post COVID-19 condition. Furthermore, it is unclear which measurement instruments are appropriate for use in research and clinical management of CYP with post-COVID-19. To address these unmet needs, we conducted a consensus study, aiming to develop a core outcome set (COS) and an associated core outcome measurement set (COMS) for evaluating post-COVID-19 condition in CYP. Our methodology comprised of two phases. In phase 1 (to create a COS), we performed an extensive literature review and categorisation of outcomes, and prioritised those outcomes in a two-round online modified Delphi process followed by a consensus meeting. In phase 2 (to create the COMS), we performed another modified Delphi consensus process to evaluate measurement instruments for previously defined "core outcomes" from phase 1, followed by an online consensus workshop to finalise recommendations regarding the most appropriate instruments for each core outcome. In phase 1, 214 participants from 37 countries participated, with 154 (72%) contributing to both Delphi rounds. The subsequent online consensus meeting resulted in a final COS which encompassed seven critical outcomes: fatigue; post-exertion symptoms; work/occupational and study changes; as well as functional changes, symptoms, and conditions relating to cardiovascular, neuro-cognitive, gastrointestinal, and physical outcomes. In phase 2, 11 international experts were involved in a modified Delphi process, selecting measurement instruments for a subsequent online consensus workshop where 30 voting participants discussed and independently scored the selected instruments. As a result of this consensus process, four instruments met a priori consensus criteria for inclusion: "PedsQL mul
Warner JO, 2024, Artificial food additives: hazardous to long-term health., Arch Dis Child
Many additives, some of which have no nutritional value, can be legally used in processed foods. They intensify colour, thicken, increase shelf life and enhance flavour. Regulatory authorities issue approvals as safe within acceptable quantitative limits. Ultra-processed foods (UPFs) contain combinations of all these additives and are particularly attractive to children.Many publications suggest that artificial colourants, benzoate preservatives, non-caloric sweeteners, emulsifiers and their degradation derivatives have adverse effects by increasing risks of mental health disorders, attention deficit hyperactivity disorder, cardiovascular disease, metabolic syndrome and potential carcinogenic effects.A systematic review has established that artificial azo dye food colourants (AFCs) and sodium benzoate preservative cause disturbed behaviour in children. AFCs and benzoates in animal models have neurotoxic properties through gut microbial generation of toxic metabolites. Observational studies show associations between high emulsifier intake and cardiovascular disease. Animal models and in vitro studies have highlighted neurotoxic, cytotoxic, genotoxic and carcinogenic effects. High intake of non-caloric sweeteners has been linked to cardiovascular disease and depression in adults and is linked to childhood obesity.Little research has focused on children who are the largest consumers of UPFs. Potentially, they are a ticking time bomb for adult obesity, metabolic syndrome, cardiovascular diseases, mental health disorders and cancers. Based on risk/benefit analysis, azo dye AFCs should be banned. Benzoates, emulsifiers and sweeteners require assessment of quantitative limits and cumulative effects of combinations. Consumers purchasing UPFs require information through ingredient health warnings and recommendations to use natural unprocessed foods which have well-described health-promoting properties.
Warner JO, 2024, Ockham's Razor: The Application of Parsimonious Medicine in Allergy/Immunology., J Allergy Clin Immunol Pract
The spectacular advances of modern medicine have distracted clinicians from applying the age-old principles of thorough history and examination followed by only ordering tests relevant to the patient's presentation. The most obvious diagnosis is the most likely and should be addressed first. Ockham's razor, or parsimonious medicine, should be applied because plurality of diagnoses is less likely than a single explanation. Component-resolved diagnostics and biological therapies for allergy/immune-mediated diseases have been highly effective when used by specialist allergy services. However, they are accessed too easily and frequently, either before diagnostically appropriate allergy skin testing and challenge have been employed or before the reasons for poor disease control have been investigated. The current fashion to test for vitamin D insufficiency in patients with poorly controlled allergic diseases has rarely achieved benefit but significantly increased costs. There are considerable health/economic benefits from following the proven value of a thorough clinical history, examination, focused allergy/immunology testing, and the judicious use of Ockham's razor.
Pazukhina E, Rumyantsev M, Baimukhambetova D, et al., 2024, Event rates and incidence of post-COVID-19 condition in hospitalised SARS-CoV-2 positive children and young people and controls across different pandemic waves: exposure-stratified prospective cohort study in Moscow (StopCOVID), BMC Medicine, Vol: 22, ISSN: 1741-7015
BACKGROUND: Long-term health outcomes in children and young people (CYP) after COVID-19 infection are not well understood and studies with control groups exposed to other infections are lacking. This study aimed to investigate the incidence of post-COVID-19 condition (PCC) and incomplete recovery in CYP after hospital discharge and compare outcomes between different SARS-CoV-2 variants and non-SARS-CoV-2 infections. METHODS: A prospective exposure-stratified cohort study of individuals under 18 years old in Moscow, Russia. Exposed cohorts were paediatric patients admitted with laboratory-confirmed COVID-19 infection between April 2 and December 11, 2020 (Wuhan variant cohort) and between January 12 and February 19, 2022 (Omicron variant cohort). CYP admitted with respiratory and intestinal infections, but negative lateral flow rapid diagnostic test and PCR-test results for SARS-CoV-2, between January 12 and February 19, 2022, served as unexposed reference cohort. Comparison between the 'exposed cohorts' and 'reference cohort' was conducted using 1:1 matching by age and sex. Follow-up data were collected via telephone interviews with parents, utilising the long COVID paediatric protocol and survey developed by the International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC). The WHO case definition was used to categorise PCC. RESULTS: Of 2595 CYP with confirmed COVID-19, 1707 (65.7%) participated in follow-up interviews, with 1183/1707 (69%) included in the final 'matched' analysis. The median follow-up time post-discharge was 6.7 months. The incidence of PCC was significantly higher in the Wuhan variant cohort (89.7 cases per 1000 person-months, 95% CI 64.3-120.3) compared to post-infection sequalae in the reference cohort (12.2 cases per 1000 person-months, 95% CI 4.9-21.9), whereas the difference with the Omicron variant cohort and reference cohort was not significant. The Wuhan cohort had higher incidence rates of dermatological, fa
Warner JO, Vazquez-Ortiz M, 2023, Transition of allergy healthcare, Current Allergy and Clinical Immunology, Vol: 36, Pages: 4-7, ISSN: 1609-3607
Because allergic diseases are long-term conditions that commonly manifest first in early life and persist in various forms well into adulthood, the transition from paediatric to adult care is an inevitable requirement. To date there has been very little focus on the requirements and wishes of young people with long-term medical problems as they transition through health services. As a consequence, there is a paucity of guidance on the way in which their transition should be conducted to optimise the outcomes and experience of these patients. The burdens encountered by patients as they are expected to develop full independence and competence to manage their own condition are superimposed on a number of physical, psychological and social challenges. Their need to achieve educational and career goals while taking control of their allergies can be overwhelming. System specialist societies and health services are beginning to resolve this problem as outcome data show that young people are particularly vulnerable to adverse events. A disproportionate number of fatalities occur in young people with severe asthma and food-induced anaphylaxis. Recommendations on the structure of this transition are being developed by national and international allergy societies. However, regional differences in health service organisation and variations in political, sociological, environmental and financial structures mean that the transition can be optimised only through locality-based implementation. The planning must involve all stakeholders, of whom young people with allergic diseases are most important. A series of recommendations are presented here which incorporate those developed by the European Academy of Allergy and Clinical Immunology together with our own additions that respond to specific challenges raised by young people.
Warner JO, 2023, PLACEBO/NOCEBO RESPONSES IN CLINICAL TRIALS AND PRACTICE, Current Allergy and Clinical Immunology, Vol: 36, Pages: 242-246, ISSN: 1609-3607
Clinicians have throughout the ages considered the enhancement of placebo effects to be part of the art of medicine. Studies to characterise placebo effects and those of its counterpart, nocebo, have identified several factors, most notably disease severity and efficiency of disease control during trial run-in periods. Milder disease or good disease control is associated with higher placebo benefits. Endogenous opioid and dopamine pathway activation have been associated with placebo responses, and genetic polymorphisms in these pathways may explain susceptibilities to placebo responsiveness. Trials in asthma have shown that placebo responses, while improving subjective symptoms, have much less effect on lung function. Giving a false sense of security to patients with severe asthma through the activation of endogenous opioids could lead to a lack of appreciation of its deterioration and could contribute to a proneness to fatality. The assumption that the placebo response is additive to that of active treatment is not proven, nor are there consistent placebo responders and non-responders. When interpreting the outcome of placebo-controlled clinical trials, design is paramount. Disease severity should be encompassed in power calculations. The run-in period should be long enough to titrate medications to the minimum required to maintain control. Having three concurrent treatment groups – active, placebo and non-intervention – can aid evaluation. Other designs may improve discrimination: these can include having a prolonged run-in on placebo with only placebo non-responders randomised to either continue placebo or commence active treatment.” The take-home message is that there is more to placebo/nocebo than meets the eye!.
Warner JO, 2023, PATIENT AND CARER INVOLVEMENT: GETTING THE BASICS OF ALLERGY PRACTICE RIGHT, Current Allergy and Clinical Immunology, Vol: 36, Pages: 216-218, ISSN: 1609-3607
Spitters SJIM, Warner JO, Reed JE, 2023, BEYOND CLINICAL GUIDELINES: HOW CARE PATHWAYS AND QUALITY-IMPROVEMENT METHODS CAN SUPPORT BETTER ALLERGY CARE, Current Allergy and Clinical Immunology, Vol: 36, Pages: 226-232, ISSN: 1609-3607
The increasing prevalence of allergic disease has resulted in the recognition of allergy as a global public health concern. Yet health services worldwide appear to be ill-equipped to deliver high-quality allergy care. Clinical guidelines have been developed to describe what high-quality care looks like for most allergic diseases. However, allergy guidelines do not describe how the delivery of such care is organised across clinicians and provider organisations with varying degrees of access to allergy expertise and clinical resources. In this article, we describe how care pathways can be used to improve the organisation and delivery of allergy care in accordance with the characteristics of allergic disease and local constraints in the health service. We then describe how quality-improvement methods can support the successful realisation of allergy care pathways in practice. Realising care pathways involves a highly complex process of changing the way care is practised and organised. This could involve developing a new service, clinical training or other interventions. Qualityimprovement methods were developed as a guide to navigate and support the process of change and improvement.
Turner P, Warner JO, 2023, Cough up, time's up: pholcodine and risk of anaphylaxis to general anaesthetics., Archives of Disease in Childhood, ISSN: 0003-9888
Munblit D, Greenhawt M, Brough HAA, 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
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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
Warner JO, 2022, Translating results from research into clinical practice, ARCHIVES OF DISEASE IN CHILDHOOD, Vol: 107, Pages: 501-502, ISSN: 0003-9888
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, 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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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
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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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, 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.
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
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