World Allergy Organization (WAO) Diagnosis and Rationale for Action against Cow's Milk Allergy (DRACMA) guideline update - XII - Recommendations on milk formula supplements with and without probiotics for infants and toddlers with CMA.

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.

Intranasal antihistamines and corticosteroids in allergic rhinitis: A systematic review and meta-analysis.

BACKGROUND: There is insufficient systematised evidence on the effectiveness of individual intranasal medications in allergic rhinitis (AR). OBJECTIVE: To perform a systematic review to compare the efficacy of individual intranasal corticosteroids and antihistamines against placebo in improving the nasal and ocular symptoms and the rhinoconjunctivitis-related quality-of-life of patients with perennial or seasonal AR. METHODS: We searched four electronic bibliographic databases and three clinical trials databases for randomised controlled trials (i) assessing adult patients with seasonal or perennial AR and (ii) comparing the use of intranasal corticosteroids or antihistamines versus placebo. Assessed outcomes included the Total Nasal Symptom Score (TNSS), the Total Ocular Symptom Score (TOSS) and the Rhinoconjunctivitis Quality-of-Life Questionnaire (RQLQ). We performed random-effects meta-analyses of mean differences for each medication and outcome. We assessed evidence certainty using the GRADE approach. RESULTS: We included 151 primary studies, most of which assessed patients with seasonal AR and displayed unclear or high risk of bias. Both in perennial and seasonal AR, most assessed treatments were more effective than placebo. In seasonal AR, azelastine-fluticasone, fluticasone furoate and fluticasone propionate were the medications with the highest probability of resulting in moderate or large improvements in the TNSS and RQLQ. Azelastine-fluticasone displayed the highest probability of resulting in moderate or large improvements of TOSS. Overall, evidence certainty was considered "high" in 6/46 analyses, "moderate" in 23/46 analyses, and "low"/"very low" in 17/46 analyses. CONCLUSION: Most intranasal medications are effective in improving rhinitis symptoms and quality-of-life. However, there are relevant differences in the associated evidence certainty.

Patients' values and preferences for health states in allergic rhinitis-An artificial intelligence supported systematic review.

BACKGROUND: Allergic rhinitis (AR) impacts patients' physical and emotional well-being. Assessing patients' values and preferences (V&P) related to AR is an essential part of patient-centered care and of the guideline development process. We aimed to systematically summarize the information about patients' V&P on AR and its symptoms and impact on daily life. METHODS: We conducted systematic review in a MEDLINE, Embase, PsychInfo, and CINAHL databases. We included studies which quantitatively assessed patients' V&P for specific outcomes in AR by assessing utilities, applying discrete choice approaches, or rating and ranking outcomes. We grouped outcomes as AR symptoms, functional status, and care-related patient experience. Study selection and data extraction were supported by the Laser AI tool. We rated the certainty of evidence (CoE) using the GRADE approach. RESULTS: Thirty-six studies (41 records) were included: nine utility studies, seven direct-choice studies and 21 studies of rating or ranking outcomes. Utilities were lower with increased AR severity and with the concomitant presence of asthma, but not with whether AR was seasonal or perennial (CoE = low-high). Patients rated AR symptom-related outcomes as more important than those related to care-related patient experience and functional status (CoE = very low-moderate). Nasal symptoms (mainly nasal congestion) followed by breathing disorders, general and ocular symptoms were rated as the symptoms with the highest impact. CONCLUSIONS: This systematic review provides a comprehensive overview of V&P of patients with AR. Patients generally considered nasal symptoms as the most important. Future studies with standardized methods are needed to provide more information on V&P in AR.

Intranasal antihistamines and corticosteroids in the treatment of allergic rhinitis: a systematic review and meta-analysis protocol.

INTRODUCTION: Intranasal antihistamines and corticosteroids are some of the most frequently used drug classes in the treatment of allergic rhinitis. However, there is uncertainty as to whether effectiveness differences may exist among different intranasal specific medications. This systematic review aims to analyse and synthesise all evidence from randomised controlled trials (RCTs) on the effectiveness of intranasal antihistamines and corticosteroids in rhinitis nasal and ocular symptoms and in rhinoconjunctivitis-related quality-of-life. METHODS AND ANALYSIS: We will search four electronic bibliographic databases and three clinical trials databases for RCTs (1) assessing patients ≥12 years old with seasonal or perennial allergic rhinitis and (2) comparing the use of intranasal antihistamines or corticosteroids versus placebo. Assessed outcomes will include the Total Nasal Symptom Score (TNSS), the Total Ocular Symptom Score (TOSS) and the Rhinoconjunctivitis Quality-of-Life Questionnaire (RQLQ). We will assess the methodological quality of included primary studies by using the Cochrane risk-of-bias tool. Certainty in the body of evidence for the analysed outcomes will be assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. We will perform a random-effects meta-analysis for each assessed medication and outcome, presenting results as pooled mean differences and standardised mean differences. Heterogeneity will be explored by sensitivity and subgroup analyses, considering (1) the risk of bias, (2) the follow-up period and (3) the drug dose. ETHICS AND DISSEMINATION: Ethical considerations will not be required. Results will be disseminated in a peer-review journal. PROSPERO REGISTRATION NUMBER: CRD42023416573.

The GIN-McMaster guideline tool extension for the integration of quality improvement and quality assurance in guidelines: a description of the methods for its development.

BACKGROUND AND OBJECTIVES: Our objective was to develop an extension of the widely used GIN-McMaster Guideline Development Checklist and Tool for the integration of quality assurance and improvement (QAI) schemes with guideline development. METHODS: We used a mixed-methods approach incorporating evidence from a systematic review, an expert workshop and a survey of experts to iteratively create an extension of the checklist for QAI through three rounds of feedback. As a part of this process, we also refined criteria of a good guideline-based quality indicator. RESULTS: We developed a 40-item checklist extension addressing steps for the integration of QAI into guideline development across the existing 18 topics and created one new topic specific to QAI. The steps span from 'organization, budget, planning and training', to updating of QAI and guideline implementation. CONCLUSION: The tool supports integration of QAI schemes with guideline development initiatives and it will be used in the forthcoming integrated European Commission Initiative on Colorectal Cancer. Future work should evaluate this extension and QAI items requiring additional support for guideline developers and links to QAI schemes.

Case studies to explore the optimal use of randomized and nonrandomized studies in evidence syntheses that use GRADE.

OBJECTIVES: Randomized controlled trials (RCTs) are the preferred source of evidence for the relative effect of healthcare interventions summarized in knowledge syntheses. Nonrandomized studies of interventions (NRSI) may provide replacement, sequential, or complementary evidence to RCTs. The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach can provide different options for properly using RCTs and NRSI integrated in health syntheses. In this article, we discuss different implications on the certainty of evidence when authors consider the use of NRSI and RCTs in systematic reviews using GRADE. Although this is a GRADE-related article, it is not an official GRADE guidance or concept article. STUDY DESIGN AND SETTING: We present case studies used during GRADE working group meetings for discussion of the effects of using NRSI and RCTs on GRADE domains and on the certainty of evidence. Several concepts were discussed through iterative feedback with experts in GRADE methods and Cochrane authors. We compared suggested solutions for possible scenarios that can be met in evidence syntheses informing decisions and future guidance. RESULTS: Different scenarios for the use of RCTs and NRSI in evidence syntheses are presented, focusing on how different GRADE ratings between RCTs and NRSI affect the overall assessment of the evidence and possible health recommendations. CONCLUSIONS: Considering differences and similarities grounded in the GRADE approach between NRSI and RCTs may help complement one another and maximize the value of knowledge syntheses and health recommendations.

World Allergy Organization (WAO) Diagnosis and Rationale for Action against Cow's Milk Allergy (DRACMA) guideline update - XIII - Oral immunotherapy for CMA - Systematic review.

Background: Allergy to cow's milk is the most common food allergy in infants and it is usually outgrown by 5 years of age. In some individuals it persists beyond early childhood. Oral immunotherapy (OIT, oral desensitization, specific oral tolerance induction) has been proposed as a promising therapeutic strategy for persistent IgE-mediated cow's milk allergy. We previously published the systematic review of OIT for cow's milk allergy (CMA) in 2010 as part of the World Allergy Organization (WAO) Diagnosis and Rationale for Action against Cow's Milk Allergy (DRACMA) Guidelines. Objective: To systematically synthesize the currently available evidence about OIT for IgE-mediated CMA and to inform the updated 2022 WAO guidelines. Methods: We searched the electronic databases including PubMed, Medline, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), and the websites of selected allergy organizations. We included all studies irrespective of the language of the original publication. The last search was conducted in February 2021. We registered the protocol on Open Science Framework (10.17605/OSF.IO/AH2DT). Results: We identified 2147 unique records published between 2010 and 2021, including 13 randomized trials and 109 observational studies addressing cow's milk OIT. We found low-certainty evidence that OIT with unheated cow's milk, compared to elimination diet alone, increased the likelihood of being able to consume ≥150 ml of cow's milk in controlled settings (risk ratio (RR): 12.3, 95% CI: 5.9 to 26.0; risk difference (RD): 25 more per 100, 95% CI 11 to 56) as well as accidently ingest a small amount (≥5 ml) of cow's milk (RR: 8.7, 95% CI: 4.7 to 16.1; RD: 25 more per 100, 95% CI 12 to 50). However, 2-8 weeks after discontinuation of a successful OIT, tolerance of cow's milk persisted in only 36% (range: 20%-91%) of patients. OIT increased the frequency of anaphylaxis (rate ratio: 60.0, 95% CI 15 to 244; rate difference 5 more anaphylactic reactions per 1 person per year, 95% CI: 4 to 6; moderate evidence) and the frequency of epinephrine use (rate ratio: 35.2, 95% CI: 9 to 136.5; rate difference 268 more events per 100 person-years, 95% CI: 203 to 333; high certainty). OIT also increased the risk of gastrointestinal symptoms (RR 6.9, 95% CI 1.6-30.9; RD 28 more per 100, CI 3 to 100) and respiratory symptoms (RR 49.0, 95% CI 3.12-770.6; RD 77 more per 100, CI 62 to 92), compared with avoidance diet alone. Single-arm observational studies showed that on average 6.9% of OIT patients (95% CI: 3.8%-10%) developed eosinophilic esophagitis (very low certainty evidence). We found 1 trial and 2 small case series of OIT with baked milk. Conclusions: Moderate certainty evidence shows that OIT with unheated cow's milk in patients with IgE-mediated CMA is associated with an increased probability of being able to drink milk and, at the same time, an increased risk of serious adverse effects.

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.

Comparison of rhinitis treatments using MASK-air® data and considering the minimal important difference.

BACKGROUND: Different treatments exist for allergic rhinitis (AR), including pharmacotherapy and allergen immunotherapy (AIT), but they have not been compared using direct patient data (i.e., "real-world data"). We aimed to compare AR pharmacological treatments on (i) daily symptoms, (ii) frequency of use in co-medication, (iii) visual analogue scales (VASs) on allergy symptom control considering the minimal important difference (MID) and (iv) the effect of AIT. METHODS: We assessed the MASK-air® app data (May 2015-December 2020) by users self-reporting AR (16-90 years). We compared eight AR medication schemes on reported VAS of allergy symptoms, clustering data by the patient and controlling for confounding factors. We compared (i) allergy symptoms between patients with and without AIT and (ii) different drug classes used in co-medication. RESULTS: We analysed 269,837 days from 10,860 users. Most days (52.7%) involved medication use. Median VAS levels were significantly higher in co-medication than in monotherapy (including the fixed combination azelastine-fluticasone) schemes. In adjusted models, azelastine-fluticasone was associated with lower average VAS global allergy symptoms than all other medication schemes, while the contrary was observed for oral corticosteroids. AIT was associated with a decrease in allergy symptoms in some medication schemes. A difference larger than the MID compared to no treatment was observed for oral steroids. Azelastine-fluticasone was the drug class with the lowest chance of being used in co-medication (adjusted OR = 0.75; 95% CI = 0.71-0.80). CONCLUSION: Median VAS levels were higher in co-medication than in monotherapy. Patients with more severe symptoms report a higher treatment, which is currently not reflected in guidelines.

World Allergy Organization (WAO) Diagnosis and Rationale for Action against Cow's Milk Allergy (DRACMA) Guideline update - XIV - Recommendations on CMA immunotherapy.

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.

Indirectness (transferability) is critical when considering existing economic evaluations for GRADE clinical practice guidelines: a systematic review.

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.

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.

World Allergy Organization (WAO) Diagnosis and Rationale for Action against Cow's Milk Allergy (DRACMA) Guidelines update - I - Plan and definitions.

Since the World Allergy Organization (WAO) Diagnosis and Rationale against Cow's Milk Allergy (DRACMA) Guidelines were published 10 years ago, new evidence has accumulated about the diagnosis, therapy, and specific immunotherapy for cow's milk allergy (CMA). For this reason, WAO has felt the need to update the guidelines. We introduce here this update. The new DRACMA guidelines aim to comprehensively address the guidance on diagnosis and therapy of both IgE non-IgE-mediated forms of cow's milk allergy in children and adults. They will be divided into 18 chapters, each of which will be dedicated to an aspect. The focus will be on the meta-analyzes and recommendations that will be expressed for the 3 most relevant clinical aspects: (a) the diagnostic identification of the condition; (b) the choice of the replacement formula in case of CMA in infancy when the mother is not able to breastfeed, and (c) the use of specific immunotherapy for cow's milk protein allergy.

A taxonomy and framework for identifying and developing actionable statements in guidelines suggests avoiding informal recommendations.

OBJECTIVE: To propose a taxonomy and framework that identifies and presents actionable statements in guidelines. STUDY DESIGN AND SETTING: We took an iterative approach reviewing case studies of guidelines produced by the World Health Organization and the American Society of Hematology to develop an initial conceptual framework. We then tested it using randomly selected recommendations from published guidelines addressing COVID-19 from different organizations, evaluated its results, and refined it before retesting. The urgency and availability of evidence for development of these recommendations varied. We consulted with experts in research methodology and guideline developers to improve the final framework. RESULTS: The resulting taxonomy and framework distinguishes five types of actional statements: formal recommendations; research recommendations; good practice statements; implementation considerations, tools and tips; and informal recommendations. These statements should respond to a priori established criteria and require a clear structure and recognizable presentation in a guideline. Most importantly, this framework identifies informal recommendations that differ from formal recommendations by how they consider evidence and in their development process. CONCLUSION: The identification, standardization and explicit labelling of actionable statements according to the framework may support guideline developers to create actionable statements with clear intent, avoid informal recommendations and improve their understanding and implementation by users.

GRADE guidance 24 optimizing the integration of randomized and non-randomized studies of interventions in evidence syntheses and health guidelines.

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.

How to write a guideline: a proposal for a manuscript template that supports the creation of trustworthy guidelines.

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.

A modeling approach to derive baseline risk estimates for GRADE recommendations: Concepts, development, and results of its application to the American Society of Hematology 2019 guidelines on prevention of venous thromboembolism in surgical hospitalized patients.

OBJECTIVE: The goal of this study was to develop an approach that can be used where baseline risk estimates that are directly applicable to prioritized patient-important outcomes are not available from published studies. STUDY DESIGN: The McMaster University GRADE Centre and the ASH guideline panel for the prevention of VTE in surgical patients developed a modeling approach based on explicit assumptions about the distribution of symptoms, anatomical location, and severity of VTE events. RESULTS: We applied the approach to derive modeled estimates of baseline risk. These estimates were used to calculated absolute measures of anticipated effects that informed the discussion of the evidence and the formulation of 30 guideline recommendations. CONCLUSION: Our approach can assist guideline developers facing a lack of information about baseline risk estimates that directly apply to outcomes of interest. The use of modeled estimates increases transparency in the process and makes the baseline risk used by guideline experts explicit during their decision-making.

Improving the quality of toxicology and environmental health systematic reviews: What journal editors can do.

Systematic reviews are fast increasing in prevalence in the toxicology and environmental health literature. However, how well these complex research projects are being conducted and reported is unclear. Since editors have an essential role in ensuring the scientific quality of manuscripts being published in their journals, a workshop was convened where editors, systematic review practitioners, and research quality control experts could discuss what editors can do to ensure the systematic reviews they publish are of sufficient scientific quality. Interventions were explored along four themes: setting standards; reviewing protocols; optimizing editorial workflows; and measuring the effectiveness of editorial interventions. In total, 58 editorial interventions were proposed. Of these, 26 were shortlisted for being potentially effective, and 5 were prioritized as short-term actions that editors could relatively easily take to improve the quality of published systematic reviews. Recent progress in improving systematic reviews is summarized, and outstanding challenges to further progress are highlighted.