World Allergy Organization (WAO) diagnosis and rationale for action against Cow\u27s milk allergy (DRACMA) guidelines update – X – breastfeeding a baby with cow\u27s milk allergy

Cow’s milk allergy is rare in exclusively breastfed infants. To support the continuation of breastfeeding an infant after diagnosis with a cow’s milk allergy, it is critical to examine the evidence for and against any form of cow’s milk elimination diet for lactating mothers. In this narrative review, we highlight the lack of high-quality evidence, hence subsequent controversy, regarding whether the minuscule quantities of cow’s milk proteins detectable in human milk cause infant cow’s milk allergy symptoms. Current clinical practice recommendations advise a 2–4 week trial of maternal cow’s milk dietary elimination for: a) IgE-mediated cow’s milk allergy only if the infant is symptomatic on breastfeeding alone; b) non-IgE-mediated associated symptoms only if the history and examination strongly suggest cow’s milk allergy; and c) infants with moderate to severe eczema/ atopic dermatitis, unresponsive to topical steroids and sensitized to cow’s milk protein. There should be a clear plan for home reintroduction of cow’s milk into the maternal diet for a period of 1 week to determine that the cow’s milk elimination is responsible for resolution of symptoms, and then subsequent reoccurrence of infant symptoms upon maternal cow’s milk reintroduction. The evidence base to support the use of maternal cow’s milk avoidance for the treatment of a breastfed infant with cow’s milk allergy is of limited strength due to a lack of high-quality, adequately powered, randomised controlled trials. It is important to consider the consequences of maternal cow’s milk avoidance on reducing immune enhancing factors in breast milk, as well as the potential nutritional and quality of life impacts on the mother. Referral to a dietitian is advised for dietary education, along with calcium and vitamin D supplementation according to local recommendations, and a maternal substitute milk should be advised. However, for most breastfed infants with cow’s milk allergy maternal cow’s milk dietary elimination will not be required, and active support of the mother to continue breastfeeding is essentia

Defining decision thresholds for judgments on health benefits and harms using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) Evidence to Decision (EtD) frameworks : A protocol for a randomised methodological study (GRADE-THRESHOLD)

Introduction The Grading of Recommendations Assessment, Development and Evaluation (GRADE) and similar Evidence to Decision (EtD) frameworks require its users to judge how substantial the effects of interventions are on desirable and undesirable people-important health outcomes. However, decision thresholds (DTs) that could help understand the magnitude of intervention effects and serve as reference for interpretation of findings are not yet available. The objective of this study is an approach to derive and use DTs for EtD judgments about the magnitude of health benefits and harms. We hypothesise that approximate DTs could have the ability to discriminate between the existing four categories of EtD judgments (Trivial, Small, Moderate, Large), support panels of decision-makers in their work, and promote consistency and transparency in judgments. Methods and analysis We will conduct a methodological randomised controlled trial to collect the data that allow deriving the DTs. We will invite clinicians, epidemiologists, decision scientists, health research methodologists, experts in Health Technology Assessment (HTA), members of guideline development groups and the public to participate in the trial. Then, we will investigate the validity of our DTs by measuring the agreement between judgments that were made in the past by guideline panels and the judgments that our DTs approach would suggest if applied on the same guideline data. Ethics and dissemination The Hamilton Integrated Research Ethics Board reviewed this study as a quality improvement study and determined that it requires no further consent. Survey participants will be required to read a consent statement in order to participate in this study at the beginning of the trial. This statement reads: You are being invited to participate in a research project which aims to identify indicative DTs that could assist users of the GRADE EtD frameworks in making judgments. Your input will be used in determining these indicative thresholds. By completing this survey, you provide consent that the anonymised data collected will be used for the research study and to be summarised in aggregate in publication and electronic tools. PROTOCOL registration number NCT05237635

Ventilation Techniques and Risk for Transmission of Coronavirus Disease, Including COVID-19 A Living Systematic Review of Multiple Streams of Evidence

Background: Mechanical ventilation is used to treat respiratory failure in coronavirus disease 2019 (COVID-19). Purpose: To review multiple streams of evidence regarding the benefits and harms of ventilation techniques for coronavirus infections, including that causing COVID-19. (PROSPERO registration: CRD42020178187) Data Sources: 21 standard, World Health Organization–specific and COVID-19–specific databases, without language restrictions, until 1 May 2020. Study Selection: Studies of any design and language comparing different oxygenation approaches in patients with coronavirus infections, including severe acute respiratory syndrome (SARS) or Middle East respiratory syndrome (MERS), or with hypoxemic respiratory failure. Animal, mechanistic, laboratory, and preclinical evidence was gathered regarding aerosol dispersion of coronavirus. Studies evaluating risk for virus transmission to health care workers from aerosol-generating procedures (AGPs) were included. Data Extraction: Independent and duplicate screening, data abstraction, and risk of bias assessment (GRADE for certainty of evidence and AMSTAR 2 for included systematic reviews). Data Synthesis: 123 studies were eligible (45 on COVID-19, 70 on SARS, 8 on MERS), but only 5 studies (1 on COVID-19, 3 on SARS, 1 on MERS) adjusted for important confounders. A study in hospitalized patients with COVID-19 reported slightly higher mortality with noninvasive ventilation (NIV) than with invasive mechanical ventilation (IMV), but 2 opposing studies, 1 in patients with MERS and 1 in patients with SARS, suggest a reduction in mortality with NIV (very low-certainty evidence). Two studies in patients with SARS report a reduction in mortality with NIV compared with no mechanical ventilation (low-certainty evidence). Two systematic reviews suggest a large reduction in mortality with NIV compared with conventional oxygen therapy. Other included studies suggest increased odds of transmission from AGPs. Limitation: Direct studies in COVID-19 are limited and poorly reported. Conclusion: Indirect and low-certainty evidence suggests that use of NIV, similar to IMV, probably reduces mortality but may increase the risk for transmission of COVID-19 to health care workers

World Allergy Organization (WAO) Diagnosis and Rationale for Action against Cow's Milk Allergy (DRACMA) Guideline update – VII – Milk elimination and reintroduction in the diagnostic process of cow's milk allergy

The diagnosis of cow's milk allergy (CMA) in infants and young children remains a challenge because many of the presenting symptoms are similar to those experienced in other diagnoses. Both over- and under-diagnosis occur frequently. Misdiagnosis carries allergic and nutritional risks, including acute reactions, growth faltering, micronutrient deficiencies and a diminished quality of life for infants and caregivers. An inappropriate diagnosis may also add a financial burden on families and on the healthcare system.Elimination and reintroduction of cow's milk (CM) and its derivatives is essential for diagnosing CMA as well as inducing tolerance to CM. In non-IgE mediated CMA, the diagnostic elimination diet typically requires 2–4 weeks before reintroduction, while for IgE mediated allergy the time window may be shorter (1–2 weeks). An oral food challenge (OFC) under medical supervision remains the most reliable diagnostic method for IgE mediated and more severe types of non-IgE mediated CMA such as food protein induced enterocolitis syndrome (FPIES). Conversely, for other forms of non-IgE mediated CMA, reintroduction can be performed at home. The OFC cannot be replaced by the milk ladder after a diagnostic elimination diet. The duration of the therapeutic elimination diet, once a diagnosis was confirmed, can only be established through testing changes in sensitization status, OFCs or home reintroduction, which are directed by local protocols and services' availability. Prior non-evidence-based recommendations suggest that the first therapeutic elimination diet should last for at least 6 months or up to the age of 9–12 months, whichever is reached first. After a therapeutic elimination diet, a milk-ladder approach can be used for non-IgE mediated allergies to determine tolerance. Whilst some centers use the milk ladder also for IgE mediated allergies, there are concerns about the risk of having immediate-type reactions at home. Milk ladders have been adapted to local dietary habits, and typically start with small amounts of baked milk which then step up in the ladder to less heated and fermented foods, increasing the allergenicity.This publication aims to narratively review the risks associated with under- and over-diagnosis of CMA, therefore stressing the necessity of an appropriate diagnosis and management

Analytical frameworks in colorectal cancer guidelines: development of methods for systematic reviews, their application and practical guidance for their use

Objectives: Analytical frameworks are graphical representation of the key questions answered by a systematic review and can support the development of guideline recommendations. Our objectives were to a) conduct a systematic review to identify, describe and compare all analytical frameworks published as part of a systematic and guideline development process related to colorectal cancer (CRC), and b) to use this case study to develop guidance on how to conduct systematic reviews of analytical frameworks. Methods: We developed a search strategy to identify eligible studies in Medline and Embase from 1996 until December 2020. We also manually searched guideline databases and websites to identify all guidelines and systematic reviews in CRC that used an analytical framework. We assessed the quality of the guidelines using the Appraisal of Guidelines for Research and Evaluation II tool. The systematic review was registered in International Prospective Register of Systematic Reviews, registration CRD42020172117. Results: We screened 34,505 records and identified 1,166 guidelines and 3,127 systematic reviews on CRC of which five met our inclusion criteria. These five publications included four analytical frameworks in colorectal cancer (one update). We also describe our methodological approach to systematic reviews for analytical frameworks and underlying concepts for developing analytical framework using a bottom-up or top-down approach. Conclusion: Few guidelines and systematic reviews are utilizing analytical frameworks in the development of recommendations. Development of analytical frameworks should begin with a systematic search for existing analytical frameworks and follow a structured conceptual approach for their development to support guideline recommendations. Our methods may be helpful in achieving these objectives

Safe management of bodies of deceased persons with suspected or confirmed COVID-19: a rapid systematic review

Introduction Proper strategies to minimise the risk of infection in individuals handling the bodies of deceased persons infected with 2019 novel coronavirus (2019-nCoV) are urgently needed. The objective of this study was to systematically review the literature to scope and assess the effects of specific strategies for the management of the bodies. Methods We searched five general, three Chinese and four coronavirus disease (COVID-19)–specific electronic databases. We searched registries of clinical trials, websites of governmental and other relevant organisations, reference lists of the included papers and relevant systematic reviews, and Epistemonikos for relevant systematic reviews. We included guidance documents providing practical advice on the handling of bodies of deceased persons with suspected or confirmed COVID-19. Then, we sought primary evidence of any study design reporting on the efficacy and safety of the identified strategies in coronaviruses. We included evidence relevant to contextual factors (ie, acceptability). A single reviewer extracted data using a pilot-tested form and graded the certainty of the evidence using the GRADE approach. A second reviewer verified the data and assessments. Results We identified one study proposing an uncommon strategy for autopsies for patients with severe acute respiratory syndrome. The study provided very low-certainty evidence that it reduced the risk of transmission. We identified 23 guidance documents providing practical advice on the steps of handling the bodies: preparation, packing, and others and advice related to both the handling of the dead bodies and the use of personal protective equipment by individuals handling them. We did not identify COVID-19 evidence relevant to any of these steps. Conclusion While a substantive number of guidance documents propose specific strategies, we identified no study providing direct evidence for the effects of any of those strategies. While this review highlights major research gaps, it allows interested entities to build their own guidance. https://creativecommons.org/licenses/by/4.0

The Risk of Allergic Reaction to SARS-CoV-2 Vaccines and Recommended Evaluation and Management: A Systematic Review, Meta-Analysis, GRADE Assessment, and International Consensus Approach

Concerns for anaphylaxis may hamper severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunization efforts. We convened a multidisciplinary group of international experts in anaphylaxis composed of allergy, infectious disease, emergency medicine, and front-line clinicians to systematically develop recommendations regarding SARS-CoV-2 vaccine immediate allergic reactions. Medline, EMBASE, Web of Science, the World Health Organizstion (WHO) global coronavirus database, and the gray literature (inception, March 19, 2021) were systematically searched. Paired reviewers independently selected studies addressing anaphylaxis after SARS-CoV-2 vaccination, polyethylene glycol (PEG) and polysorbate allergy, and accuracy of allergy testing for SARS-CoV-2 vaccine allergy. Random effects models synthesized the data to inform recommendations based on the Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) approach, agreed upon using a modified Delphi panel. The incidence of SARS-CoV-2 vaccine anaphylaxis is 7.91 cases per million (n = 41,000,000 vaccinations; 95% confidence interval [95% CI] 4.02-15.59; 26 studies, moderate certainty), the incidence of 0.15 cases per million patient-years (95% CI 0.11-0.2), and the sensitivity for PEG skin testing is poor, although specificity is high (15 studies, very low certainty). We recommend vaccination over either no vaccination or performing SARS-CoV-2 vaccine/excipient screening allergy testing for individuals without history of a severe allergic reaction to the SARS-CoV-2 vaccine/excipient, and a shared decision-making paradigm in consultation with an allergy specialist for individuals with a history of a severe allergic reaction to the SARS-CoV-2 vaccine/excipient. We recommend further research to clarify SARS-CoV-2 vaccine/vaccine excipient testing utility in individuals potentially allergic to SARS-CoV2 vaccines or their excipients