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Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/disclosure-of-interest/ and declare: support from the Canadian Institutes of Health Research for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.

Background: Cow's milk allergy (CMA) is the most common food allergy in infants. The replacement with specialized formulas is an established clinical approach to ensure adequate growth and minimize the risk of severe allergic reactions when breastfeeding is not possible. Still, given the availability of multiple options, such as extensively hydrolyzed cow's milk protein formula (eHF-CM), amino acid formula (AAF), hydrolyzed rice formula (HRF) and soy formulas (SF), there is some uncertainty as to the most suitable choice with respect to health outcomes. Furthermore, the addition of probiotics to a formula has been proposed as a potential approach to maximize benefit., Objective: These evidence-based guidelines from the World Allergy Organization (WAO) intend to support patients, clinicians, and others in decisions about the use of milk specialized formulas, with and without probiotics, for individuals with CMA., Methods: WAO formed a multidisciplinary guideline panel balanced to include the views of all stakeholders and to minimize potential biases from competing interests. The McMaster University GRADE Centre supported the guideline-development process, including updating or performing systematic evidence reviews. The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used, including GRADE Evidence-to-Decision frameworks, which were subject to review by stakeholders., Results: After reviewing the summarized evidence and thoroughly discussing the different management options, the WAO guideline panel suggests: a) using an extensively hydrolyzed (cow's milk) formula or a hydrolyzed rice formula as the first option for managing infants with immunoglobulin E (IgE) and non-IgE-mediated CMA who are not being breastfed. An amino-acid formula or a soy formula could be regarded as second and third options respectively; b) using either a formula without a probiotic or a casein-based extensively hydrolyzed formula containing Lacticaseibacillus rhamnosus GG (LGG) for infants with either IgE or non-IgE-mediated CMA.The issued recommendations are labeled as "conditional" following the GRADE approach due to the very low certainty about the health effects based on the available evidence., Conclusions: If breastfeeding is not available, clinicians, patients, and their family members might want to discuss all the potential desirable and undesirable consequences of each formula in infants with CMA, integrating them with the patients' and caregivers' values and preferences, local availability, and cost, before deciding on a treatment option. We also suggest what research is needed to determine with greater certainty which formulas are likely to be the most beneficial, cost-effective, and equitable., Competing Interests: The conduction of these guidelines was funded by WAO and the McMaster University GRADE Centre. Direct funding by for-profit companies was not accepted. The guideline panel members received travel reimbursement for attendance at in-person meetings but received no other payments. The funding was also used as salary support for the information scientist running the original searches, and for research assistants and students conducting the systematic reviews. Some members of the method team who contributed to the systematic review conduction participated without remuneration to fulfill requirements of an academic degree or program. COIs of all participants were managed according to WAO policies based on guidance by the National Academy of Medicine2 and GIN3. Before commencing the project, all the participants were asked to disclose any financial and nonfinancial interests relevant to the guidelines by completing the World Health Organization (WHO) declaration of interest forms. An independent and anonymous WAO committee revised the disclosed interests looking for COIs. The revision committee reviewed the forms and deliberated on including panel members aiming to achieve a diversity of expertise and perspectives, while minimizing the inclusion of panel members with the same or similar conflicts. Specifically, the committee placed a high value on addressing conflicts from direct financial interests from for-profit companies related to the guidelines' field. Throughout the guidelines’ development, the members of the panel and method team were asked to update the interest disclosure forms, which were again revised by the WAO committee. At the time of appointment, most of the guideline panel, including one of the guideline panel co-chair (HJS), had no conflicts of interest. The other co-chair (AF) was aware of economic support by for-profit entities provided to WAO in the form of educational grants; therefore, he abstained from voting on all recommendations in the DRACMA guidelines. The method team members deemed to have a real, potential, or perceived conflict of interest related to the topic of a systematic review were excluded from partaking in that review. Likewise, guideline panel members with manageable real, potential, or perceived conflict of interest abstained from voting on recommendations related to that interest, while being still able to provide intellectual input and clinical expertise. The Evidence-to-Decision (EtD) tables for each recommendation list individuals who were excused from voting. One proposed panel member was found with disqualifying competing interests and was excluded from the DRACMA project entirely.S Arasi, S Bahna, A Bognanni, J Brozek, D Chu, L Dahdah, P Dziechciarz, E Galli, R Kamenwa, H Li, A Martelli, R Pawankar, H Schunemann, R Targino, L Terracciano, and A Warner have no conflicts to disclose. Relationships reported related to the submitted work: IJ Anstotegui – Abbott, Amgen, Astra Zeneca, Bayer, Bial, Faes Farma, Hikma, Menarini, Merck, Mundipharma, Roxall, Sanofi, Stallergenes, UCB. A Assa'ad – Aimmune Therapeutics, DBV Technologies, Astella, ABBVIE, Novartis, Sanofi, FARE, NIH and an intellectual property patent licensed to Hoth. R Berni Canani – Ch.Hansen, Danone, DVB, Humana, iHealth, Kraft Heinz, Mead Johnson, Nestlè, Novalac, Nutricia, Sanofi. M Bozzola – Danone. C Dupont – Nestle Health Science, Nestle France, Nutricia, Novalac, Sodilac, Abbott, Danone, and stock ownership at DBV Technologies. M Ebisawa – DBV Technologies, Mylan, ARS Pharmaceuticals, Novartis. A Fiocchi – Abbott, Danone. G Lack – FARE, National Peanut Board (NPB), The Davis Foundation, Action Medical Research, UK Food Standards Agency, Medical Research Council, DBV Technologies, Mission Mighty Me, Novartis, Sanofi-Genyzme, Regeneron, ALK-Abello, Lurie Children's Hospital. A Nowak-Wegrzyn – Nestle, Nutricia, Novartis, Gerber, Aimmune. N Papadopoulos – Novartis, Nutricia, HAL Allergy, Menarini/Faes Farma, Sanofi, Mylan/Meda, Biomay, AstraZeneca, GSK, MSD, ASIT Biotech, Boehringer Ingelheim, Gerolymatos International SA, Capricare. M Said – Nestle, Nutricia, Abbott, Bayer for Anaphylaxis Australia. R Shamir - Abbott, Else, Nestle. J Spergel – DBV Technologies, Regeneron, Sanofi, and Aimmune. H Szajewska – Ausnutria, Cargill, Danone, Else Nutrition, Hipp, Nestle, and Nestle Nutrition Institute. Y Vandenplas – Abbott Nutrition, Biogaia, Biocodex, By Heart, CHR Hansen, Danone, ELSE Nutrition, Friesland Campina, Hero, Hypocrata, Nestle Health Science, Nestle Nutrition Institute, Nutricia, Mead Johnson Nutrition, Orafti, Phacobel, Phathom Pharmaceuticals, Sari Husada, United Pharmaceuticals (Novalac), Wyeth, Yakult. C Venter – Reckitt Benckiser, Nestle Nutrition Institute, Danone, Abbott Nutrition, Else Nutrition, and Before Brands, DBV Technologies. A Warner - Nutricia/Danone, Abbott, Reckitt Benckiser/Mead Johnson, Nutricia/Danone for Allergy UK. S Waserman – Novartis-basic science work on peanut allergy, Aimmune-peanut OIT trial, Medical Advisor to Food Allergy Canada, and Pfizer, Bausch, Kaleoconsultant for epinephrine autoinjectors. GWK Wong – Nestle, Danone., (© 2024 The Author(s).)

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., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objectives: Grading of Recommendations Assessment, Development and Evaluation (GRADE) practice guideline developers often perform systematic reviews of potential economic evaluations to inform recommendation decision-making. We aimed to identify indirectness characteristics of economic evaluations, related to GRADE evidence-to-decision (EtD) theoretical frameworks, that influence selection of these articles., Study Design and Setting: MEDLINE, EMBASE, CINAHL, and EconLit were systematically searched to May 2020 to identify indirectness characteristics relevant for economic evaluation transferability to GRADE EtD theoretical frameworks. Four reviewers screened citations to identify articles of any type that explored study characteristics most important or relevant to economic evaluation transferability, restricted to English language we generated frequencies of article features, used thematic analysis to summarize study characteristics, and assessed certainty in the evidence using GRADE-CERQual., Results: We included 57 articles, with a dearth of empirical literature-some may have been missed. We identified eight general themes and 28 subthemes most important to transferability from 41% of articles. Moderate-to-high confidence evidence suggested that GRADE EtD domains of population, intervention and comparison research question elements, resource use estimation and methodology, and provider and decision maker acceptability are most important indirectness study characteristics that economists consider when choosing economic evaluation outcomes for use in recommendation decision-making., Conclusion: We have identified factors important for guideline developers to consider when selecting economic evaluations as research evidence. An economic competency on the development team facilitates these endeavors. This supports the GRADE Working Group's tenant of transparent reporting or availability of sufficient information elsewhere to assess indirectness., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: The prevalence of cow's milk allergy (CMA) is approximately 2-4.5% in infants and less than 0.5% in adults. Most children outgrow cow's milk allergy in early childhood, particularly that to the baked milk products. Immunotherapy with unheated cow's milk has been used as a treatment option for those who have not yet outgrown CMA, but the benefits must be balanced with the adverse effects., Objective: These evidence-based guidelines from the World Allergy Organization (WAO) intend to support patients, clinicians, and others in decisions about the use of oral and epicutaneous immunotherapy for the treatment of IgE-mediated CMA., Methods: WAO formed a multidisciplinary guideline panel balanced to include the views of all stakeholders and to minimize potential biases from competing interests. The McMaster University GRADE Centre supported the guideline-development process, including updating or performing systematic evidence reviews. The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used, including GRADE Evidence-to-Decision frameworks, which were subject to public comment., Results: After a careful review of the summarized evidence and thorough discussions the WAO guideline panel suggests: a) using oral immunotherapy with unheated cow's milk in those individuals with confirmed IgE-mediated CMA who value the ability to consume controlled quantities of milk more than avoiding the large adverse effects of therapy, b) not using oral immunotherapy with unheated cow's milk in those who value avoiding large adverse effects of therapy more than the ability to consume controlled quantities of milk, c) using omalizumab in those starting oral immunotherapy with unheated cow's milk, d) not using oral immunotherapy with baked cow's milk in those who do not tolerate both unheated and baked milk, and e) not using epicutaneous immunotherapy outside of a research setting. The recommendations are labeled "conditional" due to the low certainty about the health effects based on the available evidence., Conclusions: Clinicians, patients, and their family members might want to discuss all the potential desirable and undesirable effects of oral immunotherapy for IgE-mediated CMA and integrate them with the patients' values and preferences before deciding on a treatment option. More robust research is needed to determine with greater certainty which interventions are likely to be the most beneficial with the least harms, and to develop safer, low-cost, and equitable treatments., (© 2022 The Authors.)

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., Competing Interests: Competing interests: HJS is the co-chair of the GRADE working group. Decision thresholds will be used in the GRADEpro app and for other projects. Currently no financial interests. HJS and JLB are codevelopers of the GRADEpro app. US is an unpaid member of Working Group for the German Clinical S3 Guideline Prevention of Cervical Cancer; Committee for Cancer Screening of the Austrian Federal Ministry of Health; Oncology Advisory Council of the Federal Ministry of Health, Austria., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Objective: This is the 24th in the ongoing series of articles describing the GRADE approach for assessing the certainty of a body of evidence in systematic reviews and health technology assessments and how to move from evidence to recommendations in guidelines., Methods: Guideline developers and authors of systematic reviews and other evidence syntheses use randomized controlled studies (RCTs) and non-randomized studies of interventions (NRSI) as sources of evidence for questions about health interventions. RCTs with low risk of bias are the most trustworthy source of evidence for estimating relative effects of interventions because of protection against confounding and other biases. However, in several instances, NRSI can still provide valuable information as complementary, sequential, or replacement evidence for RCTs., Results: In this article we offer guidance on the decision regarding when to search for and include either or both types of studies in systematic reviews to inform health recommendations., Conclusion: This work aims to help methodologists in review teams, technology assessors, guideline panelists, and anyone conducting evidence syntheses using GRADE., (Copyright © 2021. Published by Elsevier Inc.)

Trustworthy health guidelines should provide recommendations, document the development process, and highlight implementation information. Our objective was to develop a guideline manuscript template to help authors write a complete and useful report. The McMaster Grading of Recommendations Assessment, Development and Evaluation Centre collaborated with the American Society of Hematology (ASH) to develop guidelines for the management of venous thromboembolism. A template for reporting the guidelines was developed based on prior approaches and refined using input from other key stakeholders. The proposed guideline manuscript template includes: (1) title for guideline identification, (2) abstract, including a summary of key recommendations, (3) overview of all recommendations (executive summary), and (4) the main text, providing sufficient detail about the entire process, including objectives, background, and methodological decisions from panel selection and conflict-of-interest management to criteria for updating, as well as supporting information, such as links to online (interactive) tables. The template further allows for tailoring to the specific topic, using examples. Initial experience with the ASH guideline manuscript template was positive, and challenges included drafting descriptions of recommendations involving multiple management pathways, tailoring the template for a specific guideline, and choosing key recommendations to highlight. Feedback from a larger group of guideline authors and users will be needed to evaluate its usefulness and refine. The proposed guideline manuscript template is the first detailed template for transparent and complete reporting of guidelines. Consistent application of the template may simplify the preparation of an evidence-based guideline manuscript and facilitate its use., (© 2021 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Objective: Little is known about how developers and panel members report cost and cost effectiveness considerations in GRADE guideline Evidence-to-Decision (EtD) frameworks. A systematic survey was conducted to explore approaches and factors contributing to variability in economic information reporting., Study Design and Setting: Guideline organization websites were systematically searched to create a convenience sample of guidelines. Reviewers screened published EtD frameworks and generated frequencies of reporting approaches. We used thematic analysis to summarize factors related to variability of economic information reporting., Results: We included 142 guidelines. The overall rate of reporting economic information was high (91%); however, there was variability across completion of predefined EtD Likert-type judgments (70%), noting information as not identified across EtD framework domains (57%), and providing remarks to justify recommendations (38%). Six themes contributing to variability emerged, related to: intervention, population, payor, provider, healthcare resource use, and economic model building factors. Only 2 guidelines performed a GRADE certainty appraisal of economic outcomes., Conclusion: Completing predefined EtD Likert-type judgments, specifically reporting a literature review approach, study selection criteria and economic model building limitations, as well as linking these to recommendation justification remarks are potential areas for improved use, adoption and adaptation of recommendation, and transparency of GRADE EtD frameworks., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Food allergy management in child care centers and schools is a controversial topic, for which evidence-based guidance is needed. Following the Grading of Recommendations Assessment, Development, and Evaluation approach, we conducted systematic literature reviews of the anticipated health effects of selected interventions for managing food allergy in child care centers and schools; we compiled data about the costs, feasibility, acceptability, and effects on health equity of the selected interventions; and we developed the following conditional recommendations: we suggest that child care centers and schools implement allergy training and action plans; we suggest that they use epinephrine (adrenaline) to treat suspected anaphylaxis; we suggest that they stock unassigned epinephrine autoinjectors, instead of requiring students to supply their own personal autoinjectors to be stored on site for designated at-school use; and we suggest that they do not implement site-wide food prohibitions (eg, "nut-free" schools) or allergen-restricted zones (eg, "milk-free" tables), except in the special circumstances identified in this document. The recommendations are labeled "conditional" due to the low quality of available evidence. More research is needed to determine with greater certainty which interventions are likely to be the most beneficial. Policymakers might need to adapt the recommendations to fit local circumstances., (Crown Copyright © 2021. Published by Elsevier Inc. All rights reserved.)

Objective: Trauma, with resultant bleeding, is a significant cause of morbidity and mortality throughout the world; however, the best possible method of bleeding control by immediate responders is unknown. We performed a systematic review of the effectiveness of treatment modalities for severe, life-threatening external bleeding in the out-of-hospital first aid setting. Methods: We followed the Cochrane Handbook for Systematic Reviews of Interventions methodology and report results according to PRISMA guidelines. We included randomized controlled trials, non-randomized comparative studies and case series investigating adults and children with severe, life-threatening external bleeding who were treated with therapies potentially suitable for first aid providers. We assessed the certainty of the evidence and risk of bias. Outcomes were prioritized by first aid specialists based on importance for patients and decision-makers and included mortality due to bleeding, all-cause mortality, cessation of bleeding, time to cessation of bleeding, a decrease in bleeding, and complications/adverse effects. Results were reported in Evidence Profiles. Results: Of the 1,051 full-text articles screened, 107 were included for analysis including 22,798 patients. The primary methods of bleeding control were tourniquets ( n  = 49), hemostatic dressings ( n  = 34), hemostatic devices ( n  = 14), pressure dressings/bandages/devices ( n  = 8), pressure points ( n  = 4), including 2 studies that reported multiple hemorrhage control methods. Overall, certainty of evidence was very low and often relied on indirect evidence and poorly controlled studies. Tourniquets were associated with a decrease in mortality when compared with direct manual pressure. Hemostatic dressings resulted in a shorter time to hemostasis than direct manual pressure using standard dressings. Direct manual compression resulted in a shorter time to hemostasis than pressure dressings/devices. Conclusion: Overall, data regarding the control of life-threatening bleeding is of very low certainty, making it difficult to draw robust conclusions for treatment by immediate responders. While more robust data is needed on first aid treatments of life-threatening bleeding, this systematic review aggregates the most comprehensive to date to help guide recommendations. Key words: bleeding; hemorrhage; tourniquet; hemostatic dressing; direct pressure.

Objectives: Health guidelines are a key knowledge translation tool produced and used by numerous stakeholders worldwide. Effective participation in guideline development groups or development groups is crucial for guideline success, yet little guidance exists for members of these groups. In this study, we present the Guideline Participant Tool (GPT) to support effective participation in guideline groups, in particular those using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach., Study Design and Setting: We used a mixed methods and iterative approach to develop a tool to support guideline participation. We used the findings of a published systematic review to develop an initial list of items for considerations for guideline participants. Then, we refined this list through key informant interviews with guideline chairs, sponsors, and participants. Finally, we validated the GPT in three guideline groups with 26 guideline group members., Results: The initial list of items based on 37 articles from the existing systematic review included 15 themes and 61 items for a draft tool. Ten key informant interviews helped us refine the list to include the following themes: selection of participants, guideline group process, and tool format. 26 respondents completed the validation survey from three guideline groups. Refinement of the tool ultimately generated a GPT with 33 items for participant consideration before, during, and in follow-up to guideline group meetings., Conclusion: The GPT contains helpful guidance for all guideline participants, particularly those without previous guideline experience. Future research should further explore the need for additional tools to support guideline participants and identify and develop strategies for improving guideline members' participation in guideline groups. This work will be incorporated into INGUIDE.org guideline training and credentialing efforts by the Guidelines International Network and McMaster University., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: The objective of the study is to present the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) conceptual approach to the assessment of certainty of evidence from modeling studies (i.e., certainty associated with model outputs)., Study Design and Setting: Expert consultations and an international multidisciplinary workshop informed development of a conceptual approach to assessing the certainty of evidence from models within the context of systematic reviews, health technology assessments, and health care decisions. The discussions also clarified selected concepts and terminology used in the GRADE approach and by the modeling community. Feedback from experts in a broad range of modeling and health care disciplines addressed the content validity of the approach., Results: Workshop participants agreed that the domains determining the certainty of evidence previously identified in the GRADE approach (risk of bias, indirectness, inconsistency, imprecision, reporting bias, magnitude of an effect, dose-response relation, and the direction of residual confounding) also apply when assessing the certainty of evidence from models. The assessment depends on the nature of model inputs and the model itself and on whether one is evaluating evidence from a single model or multiple models. We propose a framework for selecting the best available evidence from models: 1) developing de novo, a model specific to the situation of interest, 2) identifying an existing model, the outputs of which provide the highest certainty evidence for the situation of interest, either "off-the-shelf" or after adaptation, and 3) using outputs from multiple models. We also present a summary of preferred terminology to facilitate communication among modeling and health care disciplines., Conclusion: This conceptual GRADE approach provides a framework for using evidence from models in health decision-making and the assessment of certainty of evidence from a model or models. The GRADE Working Group and the modeling community are currently developing the detailed methods and related guidance for assessing specific domains determining the certainty of evidence from models across health care-related disciplines (e.g., therapeutic decision-making, toxicology, environmental health, and health economics)., (Copyright © 2020. Published by Elsevier Inc.)

Rationale: Obesity hypoventilation syndrome (OHS) is an undesirable consequence of obesity. Weight loss is an important component of management based on clinical rationale, but the evidence supporting weight loss has not been summarized and the optimal approach has not been determined. Objectives: This systematic review informed an international, multidisciplinary panel of experts who had converged to develop a clinical practice guideline on OHS for the American Thoracic Society. The panel asked, "Should a weight loss intervention be performed in patients with OHS?" Methods: Medline, the Cochrane Library, and Embase were searched from January 1946 to March 2019 for studies that assessed weight loss interventions in obese adults with confirmed OHS, suspected OHS, or hypercapnia. The quality of the evidence was appraised using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. Results: The search identified 2,994 articles. Six studies were selected, including two randomized trials and four nonrandomized studies without a comparator. Sample size ranged from 16 to 63 subjects. The studies found that a comprehensive weight loss program (including motivational counseling, dieting, and exercise) can reduce weight by 6% to 7% but confers no clinically significant effects compared with standard care. Bariatric surgery, on the other hand, is associated with more robust weight loss (15-64.6%, depending on the type of intervention), reduction of obstructive sleep apnea severity (18-44% reduction of the apnea-hypopnea index), and improvement in gas exchange (17-20% reduction in partial pressure of carbon dioxide in the arterial blood), ultimately leading to the resolution of OHS. Moreover, daytime sleepiness and pulmonary artery pressure also improve with significant weight loss. Bariatric surgery is associated with adverse effects in roughly one-fifth of patients, but serious adverse effects are very rare. The level of certainty in the estimated effects was very low for most outcomes. Conclusions: The guideline panel for which the systematic review was performed made a conditional (i.e., weak) recommendation suggesting a weight loss intervention for patients with OHS, targeting a sustained weight loss of 25% to 30% of actual body weight. This recommendation was based on very low-quality evidence. Although the weight loss target is based on the observation that greater weight loss is associated with better outcomes, there is a need for better-quality studies to ascertain the degree of weight loss necessary to achieve improvement in clinically relevant outcomes in patients with OHS.

Rationale: Obesity hypoventilation syndrome (OHS) is an undesirable complication of severe obesity. Although weight loss is an accepted component of management, it is difficult to achieve and sustain the degree of weight loss necessary to reverse OHS. As such, positive airway pressure (PAP) during sleep has become the cornerstone therapy for most patients with OHS. However, the value of PAP therapy remains uncertain. Objective: To perform a systematic review to determine whether adults with OHS should be treated with PAP therapy or not. Methods: This systematic review informed an international, multidisciplinary panel of experts who had converged to develop a clinical practice guideline on OHS for the American Thoracic Society. MEDLINE, the Cochrane Library, and Embase were searched from January 1946 to March 2019 for studies that compared PAP therapy (i.e., continuous PAP or noninvasive ventilation) to no PAP therapy in patients with OHS. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach was used to appraise the quality of evidence. Results: The search identified 2,994 unique articles. The full text of 56 articles was reviewed, and 25 studies were selected, including 3 randomized trials, 12 nonrandomized comparative studies, and 10 randomized and nonrandomized studies without a comparator group. Sample size ranged from 21 to 1,527 patients. PAP was associated with increased resolution of OHS and improvements in mortality, gas exchange, daytime sleepiness, sleep quality, quality of life, and emergency department visits. Nearly half of patients experienced trivial adverse effects related to PAP therapy. Certainty in the estimated effects was low or very low for most outcomes. Conclusions: The panel made a conditional (i.e., weak) recommendation that PAP therapy during sleep be offered to patients with OHS to improve outcomes. This recommendation was based on very low-quality evidence.

Background: The American Thoracic Society, U.S. Centers for Disease Control and Prevention, European Respiratory Society, and Infectious Diseases Society of America jointly sponsored this new practice guideline on the treatment of drug-resistant tuberculosis (DR-TB). The document includes recommendations on the treatment of multidrug-resistant TB (MDR-TB) as well as isoniazid-resistant but rifampin-susceptible TB. Methods: Published systematic reviews, meta-analyses, and a new individual patient data meta-analysis from 12,030 patients, in 50 studies, across 25 countries with confirmed pulmonary rifampin-resistant TB were used for this guideline. Meta-analytic approaches included propensity score matching to reduce confounding. Each recommendation was discussed by an expert committee, screened for conflicts of interest, according to the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology. Results: Twenty-one Population, Intervention, Comparator, and Outcomes questions were addressed, generating 25 GRADE-based recommendations. Certainty in the evidence was judged to be very low, because the data came from observational studies with significant loss to follow-up and imbalance in background regimens between comparator groups. Good practices in the management of MDR-TB are described. On the basis of the evidence review, a clinical strategy tool for building a treatment regimen for MDR-TB is also provided. Conclusions: New recommendations are made for the choice and number of drugs in a regimen, the duration of intensive and continuation phases, and the role of injectable drugs for MDR-TB. On the basis of these recommendations, an effective all-oral regimen for MDR-TB can be assembled. Recommendations are also provided on the role of surgery in treatment of MDR-TB and for treatment of contacts exposed to MDR-TB and treatment of isoniazid-resistant TB.

Objectives: The aim of the study was to develop a Grading of Recommendations, Assessment, Development and Evaluation (GRADE) summary of findings (SoF) table format that displays the critical information from a network meta-analysis (NMA)., Study Design and Setting: We applied a user experience model for data analysis based on four rounds of semistructured interviews., Results: We interviewed 32 stakeholders who conduct or use MA. Four rounds of interviews produced six candidate NMA-SoF tables. Users found a final NMA-SoF table that included the following components highly acceptable: (1) details of the clinical question (PICO), (2) a plot depicting network geometry, (3) relative and absolute effect estimates, (4) certainty of evidence, (5) ranking of treatments, and (6) interpretation of findings., Conclusion: Using stakeholder feedback, we developed a new GRADE NMA-SoF table that includes the relevant components that facilitate understanding NMA findings and health decision-making., (Copyright © 2019. Published by Elsevier Inc.)

Background: The purpose of this guideline is to optimize evaluation and management of patients with obesity hypoventilation syndrome (OHS). Methods: A multidisciplinary panel identified and prioritized five clinical questions. The panel performed systematic reviews of available studies (up to July 2018) and followed the Grading of Recommendations, Assessment, Development, and Evaluation evidence-to-decision framework to develop recommendations. All panel members discussed and approved the recommendations. Recommendations: After considering the overall very low quality of the evidence, the panel made five conditional recommendations. We suggest that: 1 ) clinicians use a serum bicarbonate level <27 mmol/L to exclude the diagnosis of OHS in obese patients with sleep-disordered breathing when suspicion for OHS is not very high (<20%) but to measure arterial blood gases in patients strongly suspected of having OHS, 2 ) stable ambulatory patients with OHS receive positive airway pressure (PAP), 3 ) continuous positive airway pressure (CPAP) rather than noninvasive ventilation be offered as the first-line treatment to stable ambulatory patients with OHS and coexistent severe obstructive sleep apnea, 4 ) patients hospitalized with respiratory failure and suspected of having OHS be discharged with noninvasive ventilation until they undergo outpatient diagnostic procedures and PAP titration in the sleep laboratory (ideally within 2-3 mo), and 5 ) patients with OHS use weight-loss interventions that produce sustained weight loss of 25% to 30% of body weight to achieve resolution of OHS (which is more likely to be obtained with bariatric surgery). Conclusions: Clinicians may use these recommendations, on the basis of the best available evidence, to guide management and improve outcomes among patients with OHS.

Pharmacists are trusted health care professionals. Many patients use over-the-counter (OTC) medications and are seen by pharmacists who are the initial point of contact for allergic rhinitis management in most countries. The role of pharmacists in integrated care pathways (ICPs) for allergic diseases is important. This paper builds on existing studies and provides tools intended to help pharmacists provide optimal advice/interventions/strategies to patients with rhinitis. The Allergic Rhinitis and its Impact on Asthma (ARIA)-pharmacy ICP includes a diagnostic questionnaire specifically focusing attention on key symptoms and markers of the disease, a systematic Diagnosis Guide (including differential diagnoses), and a simple flowchart with proposed treatment for rhinitis and asthma multimorbidity. Key prompts for referral within the ICP are included. The use of technology is critical to enhance the management of allergic rhinitis. However, the ARIA-pharmacy ICP should be adapted to local healthcare environments/situations as regional (national) differences exist in pharmacy care., (© 2018 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Background: Prevalence of allergic diseases in infants is approximately 10% reaching 20 to 30% in those with an allergic first-degree relative. Prebiotics are selectively fermented food ingredients that allow specific changes in composition/activity of the gastrointestinal microflora. They modulate immune responses, and their supplementation has been proposed as an intervention to prevent allergies., Objective: To assess in pregnant women, breastfeeding mothers, and infants (populations) the effect of supplementing prebiotics (intervention) versus no prebiotics (comparison) on the development of allergic diseases and to inform the World Allergy Organization guidelines., Methods: We performed a systematic review of studies assessing the effects of prebiotic supplementation with an intention to prevent the development of allergies., Results: Of 446 unique records published until November 2016 in Cochrane, MEDLINE, and EMBASE, 22 studies fulfilled a priori specified criteria. We did not find any studies of prebiotics given to pregnant women or breastfeeding mothers. Prebiotic supplementation in infants, compared to placebo, had the following effects: risk of developing eczema (RR: 0.68, 95% CI: 0.40 to 1.15), wheezing/asthma (RR, 0.37; 95% CI: 0.17 to 0.80), and food allergy (RR: 0.28, 95% CI: 0.08 to 1.00). There was no evidence of an increased risk of any adverse effects (RR: 1.01, 95% CI: 0.92 to 1.10). Prebiotic supplementation had little influence growth rate (MD: 0.92 g per day faster with prebiotics, 95% CI: 0 to 1.84) and the final infant weight (MD: 0.10 kg higher with prebiotics, 95% CI: -0.09 to 0.29). The certainty of these estimates is very low due to risk of bias and imprecision of the results., Conclusions: Currently available evidence on prebiotic supplementation to reduce the risk of developing allergies is very uncertain., (© 2017 John Wiley & Sons Ltd.)

The American Thoracic Society, Centers for Disease Control and Prevention, and Infectious Diseases Society of America jointly sponsored the development of this guideline for the treatment of drug-susceptible tuberculosis, which is also endorsed by the European Respiratory Society and the US National Tuberculosis Controllers Association. Representatives from the American Academy of Pediatrics, the Canadian Thoracic Society, the International Union Against Tuberculosis and Lung Disease, and the World Health Organization also participated in the development of the guideline. This guideline provides recommendations on the clinical and public health management of tuberculosis in children and adults in settings in which mycobacterial cultures, molecular and phenotypic drug susceptibility tests, and radiographic studies, among other diagnostic tools, are available on a routine basis. For all recommendations, literature reviews were performed, followed by discussion by an expert committee according to the Grading of Recommendations, Assessment, Development and Evaluation methodology. Given the public health implications of prompt diagnosis and effective management of tuberculosis, empiric multidrug treatment is initiated in almost all situations in which active tuberculosis is suspected. Additional characteristics such as presence of comorbidities, severity of disease, and response to treatment influence management decisions. Specific recommendations on the use of case management strategies (including directly observed therapy), regimen and dosing selection in adults and children (daily vs intermittent), treatment of tuberculosis in the presence of HIV infection (duration of tuberculosis treatment and timing of initiation of antiretroviral therapy), as well as treatment of extrapulmonary disease (central nervous system, pericardial among other sites) are provided. The development of more potent and better-tolerated drug regimens, optimization of drug exposure for the component drugs, optimal management of tuberculosis in special populations, identification of accurate biomarkers of treatment effect, and the assessment of new strategies for implementing regimens in the field remain key priority areas for research. See the full-text online version of the document for detailed discussion of the management of tuberculosis and recommendations for practice., (© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.)

The American Thoracic Society, Centers for Disease Control and Prevention, and Infectious Diseases Society of America jointly sponsored the development of this guideline for the treatment of drug-susceptible tuberculosis, which is also endorsed by the European Respiratory Society and the US National Tuberculosis Controllers Association. Representatives from the American Academy of Pediatrics, the Canadian Thoracic Society, the International Union Against Tuberculosis and Lung Disease, and the World Health Organization also participated in the development of the guideline. This guideline provides recommendations on the clinical and public health management of tuberculosis in children and adults in settings in which mycobacterial cultures, molecular and phenotypic drug susceptibility tests, and radiographic studies, among other diagnostic tools, are available on a routine basis. For all recommendations, literature reviews were performed, followed by discussion by an expert committee according to the Grading of Recommendations, Assessment, Development and Evaluation methodology. Given the public health implications of prompt diagnosis and effective management of tuberculosis, empiric multidrug treatment is initiated in almost all situations in which active tuberculosis is suspected. Additional characteristics such as presence of comorbidities, severity of disease, and response to treatment influence management decisions. Specific recommendations on the use of case management strategies (including directly observed therapy), regimen and dosing selection in adults and children (daily vs intermittent), treatment of tuberculosis in the presence of HIV infection (duration of tuberculosis treatment and timing of initiation of antiretroviral therapy), as well as treatment of extrapulmonary disease (central nervous system, pericardial among other sites) are provided. The development of more potent and better-tolerated drug regimens, optimization of drug exposure for the component drugs, optimal management of tuberculosis in special populations, identification of accurate biomarkers of treatment effect, and the assessment of new strategies for implementing regimens in the field remain key priority areas for research. See the full-text online version of the document for detailed discussion of the management of tuberculosis and recommendations for practice., (© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.)

Background: Lymphangioleiomyomatosis (LAM) is a rare cystic lung disease that primarily affects women. The purpose of these guidelines is to provide recommendations for the diagnosis and treatment of LAM., Methods: Systematic reviews were performed to summarize evidence pertinent to our questions. The evidence was summarized and discussed by a multidisciplinary panel. Evidence-based recommendations were then formulated, written, and graded using the Grading of Recommendations, Assessment, Development, and Evaluation approach., Results: After considering the panel's confidence in the estimated effects, the balance of desirable (i.e., benefits) and undesirable (i.e., harms and burdens) consequences of treatment, patient values and preferences, cost, and feasibility, recommendations were formulated for or against specific interventions. These included recommendations for sirolimus treatment and vascular endothelial growth factor D testing and recommendations against doxycycline and hormonal therapy., Conclusions: Evidence-based recommendations for the diagnosis and treatment of patients with LAM are provided. Frequent reassessment and updating will be needed.

It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients or special clinical situations. IDSA considers adherence to these guidelines to be voluntary, with the ultimate determination regarding their application to be made by the physician in the light of each patient's individual circumstances.These guidelines are intended for use by healthcare professionals who care for patients at risk for hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP), including specialists in infectious diseases, pulmonary diseases, critical care, and surgeons, anesthesiologists, hospitalists, and any clinicians and healthcare providers caring for hospitalized patients with nosocomial pneumonia. The panel's recommendations for the diagnosis and treatment of HAP and VAP are based upon evidence derived from topic-specific systematic literature reviews., (© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.)

It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients or special clinical situations. IDSA considers adherence to these guidelines to be voluntary, with the ultimate determination regarding their application to be made by the physician in the light of each patient's individual circumstances.These guidelines are intended for use by healthcare professionals who care for patients at risk for hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP), including specialists in infectious diseases, pulmonary diseases, critical care, and surgeons, anesthesiologists, hospitalists, and any clinicians and healthcare providers caring for hospitalized patients with nosocomial pneumonia. The panel's recommendations for the diagnosis and treatment of HAP and VAP are based upon evidence derived from topic-specific systematic literature reviews., (© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.)

Objectives: The current format of summary of findings (SoFs) tables for presenting effect estimates and associated quality of evidence improve understanding and assist users finding key information in systematic reviews. Users of SoF tables have demanded alternative formats to express findings from systematic reviews., Study Design and Setting: We conducted a randomized controlled trial among systematic review users to compare the relative merits of a new format with the current formats of SoF tables regarding understanding, accessibility of information, satisfaction, and preference. Our primary goal was to show that the new format is not inferior to the current format., Results: Of 390 potentially eligible subjects, 290 were randomized. Of seven items testing understanding, three showed similar results, two showed small differences favoring the new format, and two (understanding risk difference and quality of the evidence associated with a treatment effect) showed large differences favoring the new format [63% (95% confidence interval {CI}: 55, 71) and 62% (95% CI: 52, 71) more correct answers, respectively]. Respondents rated information in the alternative format as more accessible overall and preferred the new format over the current format., Conclusions: While providing at least similar levels of understanding for some items and increased understanding for others, users prefer the new format of SoF tables., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: The Grading of Recommendations Assessment, Development and Evaluation (GRADE) is widely used and reliable and accurate for assessing the certainty in the body of health evidence. The GRADE working group has provided detailed guidance for assessing the certainty in the body of evidence in systematic reviews and health technology assessments (HTAs) and how to grade the strength of health recommendations. However, there is limited advice regarding how to maximize transparency of these judgments, in particular through explanatory footnotes or explanations in Summary of Findings tables and Evidence Profiles (GRADE evidence tables)., Methods: We conducted this study to define the essential attributes of useful explanations and to develop specific guidance for explanations associated with GRADE evidence tables. We used a sample of explanations according to their complexity, type of judgment involved, and appropriateness from a database of published GRADE evidence tables in Cochrane reviews and World Health Organization guidelines. We used an iterative process and group consensus to determine the attributes and develop guidance., Results: Explanations in GRADE evidence tables should be concise, informative, relevant, easy to understand, and accurate. We provide general and domain-specific guidance to assist authors with achieving these desirable attributes in their explanations associated with GRADE evidence tables., Conclusions: Adhering to the general and GRADE domain-specific guidance should improve the quality of explanations associated with GRADE evidence tables, assist authors of systematic reviews, HTA reports, or guidelines with information that they can use in other parts of their evidence synthesis. This guidance will also support editorial evaluation of evidence syntheses using GRADE and provide a minimum quality standard of judgments across tables., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Children with chronic invasive ventilator dependence living at home are a diverse group of children with special health care needs. Medical oversight, equipment management, and community resources vary widely. There are no clinical practice guidelines available to health care professionals for the safe hospital discharge and home management of these complex children., Purpose: To develop evidence-based clinical practice guidelines for the hospital discharge and home/community management of children requiring chronic invasive ventilation., Methods: The Pediatric Assembly of the American Thoracic Society assembled an interdisciplinary workgroup with expertise in the care of children requiring chronic invasive ventilation. The experts developed four questions of clinical importance and used an evidence-based strategy to identify relevant medical evidence. Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology was used to formulate and grade recommendations., Results: Clinical practice recommendations for the management of children with chronic ventilator dependence at home are provided, and the evidence supporting each recommendation is discussed., Conclusions: Collaborative generalist and subspecialist comanagement is the Medical Home model most likely to be successful for the care of children requiring chronic invasive ventilation. Standardized hospital discharge criteria are suggested. An awake, trained caregiver should be present at all times, and at least two family caregivers should be trained specifically for the child's care. Standardized equipment for monitoring, emergency preparedness, and airway clearance are outlined. The recommendations presented are based on the current evidence and expert opinion and will require an update as new evidence and/or technologies become available.

Coexistence of multiple chronic conditions (i.e., multimorbidity) is the most common chronic health problem in adults. However, clinical practice guidelines have primarily focused on patients with a single disease, resulting in uncertainty about the care of patients with multimorbidity. The American Thoracic Society convened a workshop with the goal of establishing a strategy to address multimorbidity within clinical practice guidelines. In this Workshop Report, we describe a framework that addresses multimorbidity in each of the key steps of guideline development: topic selection, panel composition, identifying clinical questions, searching for and synthesizing evidence, rating the quality of that evidence, summarizing benefits and harms, formulating recommendations, and rating the strength of the recommendations. For the consideration of multimorbidity in guidelines to be successful and sustainable, the process must be both feasible and pragmatic. It is likely that this will be achieved best by the step-wise addition and refinement of the various components of the framework.

Background: This document updates the American Thoracic Society/European Respiratory Society/Japanese Respiratory Society/Latin American Thoracic Association guideline on idiopathic pulmonary fibrosis treatment., Methods: Systematic reviews and, when appropriate, meta-analyses were performed to summarize all available evidence pertinent to our questions. The evidence was assessed using the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach and then discussed by a multidisciplinary panel. Predetermined conflict-of-interest management strategies were applied, and recommendations were formulated, written, and graded exclusively by the nonconflicted panelists., Results: After considering the confidence in effect estimates, the importance of outcomes studied, desirable and undesirable consequences of treatment, cost, feasibility, acceptability of the intervention, and implications to health equity, recommendations were made for or against specific treatment interventions., Conclusions: The panel formulated and provided the rationale for recommendations in favor of or against treatment interventions for idiopathic pulmonary fibrosis.

Background: Systematic reviews represent one of the most important tools for knowledge translation but users often struggle with understanding and interpreting their results. GRADE Summary-of-Findings tables have been developed to display results of systematic reviews in a concise and transparent manner. The current format of the Summary-of-Findings tables for presenting risks and quality of evidence improves understanding and assists users with finding key information from the systematic review. However, it has been suggested that additional methods to present risks and display results in the Summary-of-Findings tables are needed., Methods/design: We will conduct a non-inferiority parallel-armed randomized controlled trial to determine whether an alternative format to present risks and display Summary-of-Findings tables is not inferior compared to the current standard format. We will measure participant understanding, accessibility of the information, satisfaction, and preference for both formats. We will invite systematic review users to participate (that is clinicians, guideline developers, and researchers). The data collection process will be undertaken using the online 'Survey Monkey' system. For the primary outcome understanding, non-inferiority of the alternative format (Table A) to the current standard format (Table C) of Summary-of-Findings tables will be claimed if the upper limit of a 1-sided 95% confidence interval (for the difference of proportion of participants answering correctly a given question) excluded a difference in favor of the current format of more than 10%., Discussion: This study represents an effort to provide systematic reviewers with additional options to display review results using Summary-of-Findings tables. In this way, review authors will have a variety of methods to present risks and more flexibility to choose the most appropriate table features to display (that is optional columns, risks expressions, complementary methods to display continuous outcomes, and so on)., Trials Registration: NCT02022631 (21 December 2013).