Severity and mortality associated with COVID-19 among children hospitalised in tertiary care centres in India: a cohort study.

Background: It is critical to identify high-risk groups among children with COVID-19 from low-income and middle-income countries (LMICs) to facilitate the optimum use of health system resources. The study aims to describe the severity and mortality of different clinical phenotypes of COVID-19 in a large cohort of children admitted to tertiary care hospitals in India. Methods: Children aged 0-19 years with evidence of SARS-CoV-2 infection (real time polymerase chain reaction or rapid antigen test positive) or exposure (anti-SARS-CoV-2 antibody, or history of contact with SARS-CoV-2) were enrolled in the study, between January 2021 and March 2022 across five tertiary hospitals in India. All study participants enrolled prospectively and retrospectively were followed up for three months after discharge. COVID-19 was classified into severe (Multisystem Inflammatory Syndrome in Children (MIS-C), severe acute COVID-19, 'unclassified') or non-severe disease. The mortality rates were estimated in different phenotypes. Findings: Among 2468 eligible children enrolled, 2148 were hospitalised. Signs of illness were present in 1688 (79%) children with 1090 (65%) having severe disease. High mortality was reported in MIS-C (18.6%), severe acute COVID-19 (13.3%) and the unclassified severe COVID-19 disease (12.3%). Mortality remained high (17.5%) when modified MIS-C criteria was used. Non-severe COVID-19 disease had 14.1% mortality when associated with comorbidity. Interpretation: Our findings have important public health implications for low resource settings. The high mortality underscores the need for better preparedness for timely diagnosis and management of COVID-19. Children with associated comorbidity or coinfections are a vulnerable group and need special attention. MIS-C requires context specific diagnostic criteria for low resource settings. It is important to evaluate the clinical, epidemiological and health system-related risk factors associated with severe COVID-19 and mortality in children from LMICs. Funding: Department of Biotechnology, Govt of India and Department of Maternal, Child and Adolescent Health and Aging, WHO, Geneva, Switzerland.

Congenital syphilis: a rare presentation of a forgotten infection.

Congenital syphilis (CS), a common but forgotten disease has a broad spectrum of clinical presentation. Vertical transmission of this spirochaetal infection from the pregnant mother to the foetus can result in varied manifestations ranging from asymptomatic infection to life- threatening conditions in the form of stillbirth and neonatal death. The haematological and visceral manifestations of this disease can closely mimic various conditions including haemolytic anaemia and malignancies. Congenital syphilis should be considered as a differential in any infant presenting with hepatosplenomegaly and haematological abnormalities even if the antenatal screen was negative. We report a 6-month-old infant with congenital syphilis presenting with organomegaly, bicytopenia and monocytosis. A strong index of suspicion and early diagnosis is the key to the good outcome as treatment is simple and cost- effective.

Indian Academy of Pediatrics Consensus Guidelines on Prevention and Management of Suicidal Behavior in Adolescents.

JUSTIFICATION: Suicide is an important cause of adolescent mortality and morbidity in India. As pediatricians are often the first point of contact for adolescents and their families in the healthcare system, they need guidelines to screen, assess, manage and prevent adolescent suicidal behavior to ensure survival, health and mental well-being of this vulnerable population. OBJECTIVES: To formulate guidelines to aid pediatricians for prevention and management of adolescent suicidal behavior. PROCESS: Indian Academy of Pediatrics, in association with Adolescent Health Academy, formed a multidisciplinary committee of subject experts in June, 2019 to formulate guidelines for adolescent suicide prevention and management. After a review of current scientific literature and preparation of draft guidelines, a national consultative meeting was organized on 16 August, 2019 for detailed discussions and deliberations. This was followed by refining of draft guidelines, and discussions over e-mail where suggestions were incorporated and the final document was approved. GUIDELINES: Pediatricians should screen for mental distress, mental disorders and suicidal and para-suicidal (non-suicidal self-injury) behavior during adolescent health visits. Those with suicidal behavior should be referred to a psychiatrist after providing emergency healthcare, risk assessment, immediate counselling and formulation of a safety plan. Pediatricians should partner with the community and policymakers for primary and secondary prevention of adolescent suicide.

Indian Academy of Pediatrics Consensus Guidelines for Adolescent Friendly Health Services.

JUSTIFICATION: Adolescent health is critical to the current and future well- being of the world. Pediatricians need country specific guidelines in accordance with international and national standards to establish comprehensive adolescent friendly health services in clinical practice. PROCESS: Indian Academy of Pediatrics (IAP) in association with Adolescent Health Academy formed a committee of subject experts in June, 2019 to formulate guidelines for adolescent friendly health services. After a review of current scientific literature and drafting guidelines on each topic, a national consultative meeting was organized on 16 August, 2019 for detailed discussions and deliberations. This was followed by discussions over e-mail and refining of draft recommendations. The final guidelines were approved by the IAP Executive Board in December, 2021. OBJECTIVE: To formulate guidelines to enable pediatricians to establish adolescent friendly health services. Recommendations: Pediatricians should coordinate healthcare for adolescents and plan for transition of care to an adult physician by 18 years of age. Pediatricians should establish respectful, confidential and quality adolescent friendly health services for both out-patient and in-patient care. The healthcare facility should provide preventive, therapeutic, and health promoting services. Pediatricians should partner with the multidisciplinary speciality services, community, and adolescents to expand the scope and reach of adolescent friendly health services.

Biologics for Asthma and Allergic Skin Diseases in Children.

An estimated 7 million children in the United States have asthma, which causes a significant health care burden and affects quality of life. The minority of these children have asthma that does not respond to Global Initiative for Asthma steps 4 and 5 care, and biological medications are recommended at this level in the 2019 Global Initiative for Asthma recommendations. In addition, biologics have been introduced into the care of children with allergic skin diseases. Omalizumab and mepolizumab are approved for children as young as 6 years, and benralizumab and dupilumab are approved for people aged ≥12 years. Reslizumab is approved only for people aged ≥18 years. These monoclonal antibodies may be added for appropriate patients when asthma or allergic skin diseases are not well controlled. Pediatricians and pediatric subspecialists should work together and be aware of the benefits and risks of these medications for their patients, as well as the practical implications of providing these options for their patients. This clinical report serves as an evaluation of the current literature on these types of medications in the treatment of children with asthma and allergic skin disease.

Peanut allergy diagnosis: A 2020 practice parameter update, systematic review, and GRADE analysis.

Given the burden of disease and the consequences of a diagnosis of peanut allergy, it is important that peanut allergy be accurately diagnosed so that an appropriate treatment plan can be developed. However, a test that indicates there is peanut sensitization present (eg, a "positive" test) is not always associated with clinical reactivity. This practice parameter addresses the diagnosis of IgE-mediated peanut allergy, both in children and adults, as pertaining to 3 fundamental questions, and based on the systematic reviews and meta-analyses, makes recommendations for the clinician who is evaluating a patient for peanut allergy. These questions relate to when diagnostic tests should be completed, which diagnostic tests to utilize, and the utility (or lack thereof) of diagnostic testing to predict the severity of a future allergic reaction to peanut.

Rhinitis 2020: A practice parameter update.

This comprehensive practice parameter for allergic rhinitis (AR) and nonallergic rhinitis (NAR) provides updated guidance on diagnosis, assessment, selection of monotherapy and combination pharmacologic options, and allergen immunotherapy for AR. Newer information about local AR is reviewed. Cough is emphasized as a common symptom in both AR and NAR. Food allergy testing is not recommended in the routine evaluation of rhinitis. Intranasal corticosteroids (INCS) remain the preferred monotherapy for persistent AR, but additional studies support the additive benefit of combination treatment with INCS and intranasal antihistamines in both AR and NAR. Either intranasal antihistamines or INCS may be offered as first-line monotherapy for NAR. Montelukast should only be used for AR if there has been an inadequate response or intolerance to alternative therapies. Depot parenteral corticosteroids are not recommended for treatment of AR due to potential risks. While intranasal decongestants generally should be limited to short-term use to prevent rebound congestion, in limited circumstances, patients receiving regimens that include an INCS may be offered, in addition, an intranasal decongestant for up to 4 weeks. Neither acupuncture nor herbal products have adequate studies to support their use for AR. Oral decongestants should be avoided during the first trimester of pregnancy. Recommendations for use of subcutaneous and sublingual tablet allergen immunotherapy in AR are provided. Algorithms based on a combination of evidence and expert opinion are provided to guide in the selection of pharmacologic options for intermittent and persistent AR and NAR.

Making the GRADE in anaphylaxis management: Toward recommendations integrating values, preferences, context, and shared decision making.

OBJECTIVE: To review GRADE (Grading of Recommendations Assessment, Development, and Evaluation) methods and discuss the clinical application of conditional recommendations in clinical guidelines, specifically in the context of anaphylaxis. DATA SOURCES: Articles that described GRADE, evidence synthesis, evidence to recommendation frameworks, and shared decision making were used to discuss conditional recommendations of the 2020 Anaphylaxis GRADE guideline. STUDY SELECTIONS: A narrative review detailing concepts of GRADE and approaches to translate conditional recommendations to individualized and contextualized patient care. RESULTS: GRADE methods encourage a nuanced relationship between certainty of evidence and strength of recommendations. Strength of recommendation must incorporate key factors, including the balance between benefits and harms, patient values and preferences, and resource allocation (costs), with equity, feasibility, and acceptability also often included as considerations. GRADE guidelines provide recommendations that are characterized by directionality (for or against) and strength (strong or conditional). A conditional recommendation is tailored to context and primarily applied through a lens of patient preferences related to the likelihood of outcomes of importance and a shared decision-making approach. Although the 2020 Anaphylaxis GRADE guideline better informs the practice of anaphylaxis prevention through (1) identification and mitigation of risk factors for biphasic anaphylaxis and (2) evaluation of the use of glucocorticoid and/or antihistamine pretreatment, all GRADE recommendations, although directional, are conditional and as such should not be universally applied to every circumstance. CONCLUSION: Clinical guidelines provide an important opportunity to critically appraise evidence and translate evidence to practice. Patients, practitioners, and policy makers should appreciate the strength of recommendation and certainty of evidence and understand how this affects guideline applicability and implementation.

Anaphylaxis-a 2020 practice parameter update, systematic review, and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) analysis.

Anaphylaxis is an acute, potential life-threatening systemic allergic reaction that may have a wide range of clinical manifestations. Severe anaphylaxis and/or the need for repeated doses of epinephrine to treat anaphylaxis are risk factors for biphasic anaphylaxis. Antihistamines and/or glucocorticoids are not reliable interventions to prevent biphasic anaphylaxis, although evidence supports a role for antihistamine and/or glucocorticoid premedication in specific chemotherapy protocols and rush aeroallergen immunotherapy. Evidence is lacking to support the role of antihistamines and/or glucocorticoid routine premedication in patients receiving low- or iso-osmolar contrast material to prevent recurrent radiocontrast media anaphylaxis. Epinephrine is the first-line pharmacotherapy for uniphasic and/or biphasic anaphylaxis. After diagnosis and treatment of anaphylaxis, all patients should be kept under observation until symptoms have fully resolved. All patients with anaphylaxis should receive education on anaphylaxis and risk of recurrence, trigger avoidance, self-injectable epinephrine education, referral to an allergist, and be educated about thresholds for further care.

Unmet needs of children with peanut allergy: Aligning the risks and the evidence.

BACKGROUND: Peanut allergy is a potentially severe and lifelong allergy, with few effective treatments or preventive measures. OBJECTIVE: To convene an expert panel of allergists, pediatricians, and advocates to discuss and highlight unmet needs in the prevention and management of peanut allergies. METHODS: Literature searches of PubMed were performed. The panel evaluated published data on the prevention of peanut allergy, treatment of existing peanut allergy, and management of reactions after unintentional peanut exposures. RESULTS: The following key unmet needs in the prevention and management of peanut allergy were identified: (1) enhancing and optimizing implementation of early peanut introduction as a means of preventing the development of peanut allergy, (2) developing knowledge translation strategies regarding the safety and efficacy data for current and emerging immunotherapies for peanut-allergic children to support their use in clinical practice, and (3) promoting understanding of true exposure risk in allergic individuals and ensuring access to epinephrine for unintentional exposures that provoke severe reactions. Practitioners should help educate caregivers about the actual risks associated with peanut allergy and its prevention and management so that treatment decisions can be evidence based rather than fear based. Support tools are needed to help address caregiver goals, expectations, and psychological barriers, as well as identify facilitators for prevention and treatment strategies. CONCLUSION: There are significant unmet needs in our understanding of peanut allergy; addressing these needs will help to enhance understanding of how to most effectively prevent and treat peanut allergy, as well as educate the food-allergic and nonallergic community regarding current evidence-based practices.

From the Pages of Allergy Watch: November 2019.

A new Annals feature in 2018, "From the Pages of AllergyWatch" is devoted to publishing synopses of Allergy and Asthma literature relevant to a topic of emphasis. These unbiased synopses and comments by our Editors have been previously printed in the AllergyWatch bimonthly newsletter, and it is our hope that presenting carefully selected article summaries and comments in the Annals will serve as a valuable educational resource for practicing allergists.

Are PPIs beneficial for nasal polyps?

A new Annals feature in 2018, "From the Pages of AllergyWatch" is devoted to publishing synopses of Allergy and Asthma literature relevant to a topic of emphasis. These unbiased synopses and comments by our Editors have been previously printed in the AllergyWatch bimonthly newsletter, and it is our hope that presenting carefully selected article summaries and comments in the Annals will serve as a valuable educational resource for practicing allergists.

Chronic Mucocutaneous Candidiasis in an Adolescent Boy Due to a Novel Mutation in TRAF3IP2.

BACKGROUND: IL-17-mediated signaling is crucial in defense against fungi and bacteria. Defective Th17 immunity has been implicated in a group of disorders called chronic mucocutaneous candidiasis (CMC). TRAF3IP2 is an adaptor protein involved in downstream signaling for IL-17 receptors. CASE: An 18-year-old boy, product of consanguineous wedlock, presented with history of repeated episodes of oral thrush and recurrent pneumonia from first year of life. On examination, he was wasted and had oral thrush and abnormal dentition; grade 2 clubbing and respiratory system examination revealed coarse crepitations. On evaluation, HIV status was negative and basic immunological screen was unrewarding. Genetic testing by next-generation sequencing showed a novel homozygous mutation in TRAF3IP2 gene not reported to date. The defect is likely to cause ACT1 deficiency. He was started on antibiotic and antifungal prophylaxis and remains well on follow-up. CONCLUSION: We describe an adolescent boy with recurrent oral candidiasis and bronchiectasis due to a novel mutation in TRAF3IP2 gene, not reported to date. This is also the only second report of CMC due to ACT1 deficiency.

AllergyWatch.

A new Annals feature in 2018, "From the Pages of AllergyWatch" is devoted to publishing synopses of Allergy and Asthma literature relevant to a topic of emphasis. These unbiased synopses and comments by our Editors have been previously printed in the AllergyWatch bimonthly newsletter, and it is our hope that presenting carefully selected article summaries and comments in the Annals will serve as a valuable educational resource for practicing allergists. For this issue of 'From the Pages of Allergy Watch' articles are presented that coincide with the theme of this month's Annals. The first article addresses the impact of allergic rhinitis on work productivity in affected patients. The second article review data from a large number of children presenting to Canadian emergency departments with asthma exacerbations and the impact of certain viral pathogens. The last article reviewed investigates data showing that patients who 'run out' of asthma inhalers were more likely to present to the emergency room for their asthma care.