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Objectives: The evaluation of health benefits and harms of an intervention with GRADE Evidence to Decision (EtD) frameworks includes judgments if the effects are "trivial," "small," "moderate," or "large." Such judgments ideally require the a priori establishment of decision thresholds (DTs), whose empirical derivation for single outcomes has been previously described. In this article, we provide a methodological approach to estimate DTs for composite endpoints based on disutilities., Study Design and Setting: We generated an approach that involves the computation of pooled disutilities, in which the disutility of each outcome comprised in the composite endpoint is weighted by the respective relative frequency. We also applied a modeling approach based on probability distributions to account for uncertainty in the estimates. We present a practical example of the determination of DTs associated with the development of at least one adverse event following treatment with intranasal medications for rhinitis that we used in the Allergic Rhinitis and its Impact on Asthma guidelines., Results: We provide the methodological steps of a modeling-based approach to compute pooled disutilities and, as a result, DTs for composite endpoints. We have developed a webtool (https://compositedt.med.up.pt/) that allows for a simple implementation of the proposed approach. Applying our approach to a practical example, we concluded that rhinitis nasal medications, compared to placebo, were associated with a trivial harm from adverse events., Conclusion: We propose an approach for estimating DTs for composite endpoints, which may be particularly valuable whenever composite endpoints are used for clinical research, clinical practice, and decision-making., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Treatments for allergic rhinitis include intranasal or oral medications., Objective: To perform a systematic review with meta-analysis comparing the effectiveness of intranasal corticosteroids or antihistamines versus oral antihistamines or leukotriene receptor antagonists in improving allergic rhinitis symptoms and quality of life., Methods: We searched four bibliographic databases and three clinical trial datasets for randomized controlled trials (1) assessing patients aged 12 years and older with seasonal or perennial allergic rhinitis, and (2) comparing intranasal corticosteroids or antihistamines versus oral antihistamines or leukotriene receptor antagonists. We performed a meta-analysis of the Total Nasal Symptom Score (TNSS), Total Ocular Symptom Score, Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ), development of adverse events, and withdrawals owing to adverse events. Certainty of evidence was assessed using Grading of Recommendations, Assessment, Development, and Evaluation., Results: We included 35 studies, most of which assessed patients with seasonal allergic rhinitis and displayed an unclear risk of bias. Superiority of intranasal treatments was found for all assessed outcomes. Intranasal corticosteroids were more effective than oral antihistamines at improving the TNSS (mean difference [MD], -0.86; 95% CI, -1.21 to -0.51; I 2  = 70%), Total Ocular Symptom Score (MD, -0.36; 95% CI, -0.56 to -0.17; I 2  = 0%), and RQLQ (MD, -0.88; 95% CI, -1.15 to -0.61; I 2  = 0%), which were mostly associated with clinically meaningful improvements. Superiority of intranasal corticosteroids at improving the TNSS was also found against oral leukotriene receptor antagonists (MD, -1.05; 95% CI, -1.33 to -0.77). Intranasal antihistamines were more effective than oral antihistamines at improving the TNSS (MD, -0.47; 95% CI, -0.81 to -0.14; I 2  = 0%) and RQLQ (MD, -0.31; 95% CI, -0.56 to -0.06; I 2  = 0%)., Conclusions: Randomized controlled trials suggest that intranasal treatments are more effective than oral treatments at improving symptoms and quality of life in seasonal allergic rhinitis., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background and Objective: Grading of Recommendations, Assessment, Development, and Evaluation (GRADE)-ADOLOPMENT is widely applied to efficiently use existing credible guidelines and contextualize them to a target setting. To highlight the experiences of a Latin American Guideline Development Group (GDG) applying GRADE-ADOLOPMENT to adapt the American Society of Hematology's clinical practice guideline on managing venous thromboembolisms (VTEs) in Latin America., Study Design and Setting: We employed a mixed-method postevaluation using self-administered surveys and semistructured interviews. We assessed the Latin American GDG (1) general satisfaction and confidence using the approach, (2) their ratings on the usefulness, appropriateness, and importance of GRADE-ADOLOPMENT and its tools to inform their judgements, and (3) any additional facilitators and barriers to refine the process., Results: Eleven of the 14 GDG members, including nine panelists and two methodologists, provided survey responses and eight participated in the interview. Respondents felt "mostly" or "completely" satisfied with the adapted guideline. Eight panelists who were surveyed agree that GRADE-ADOLOPMENT is useful in countries with limited resources. Although panelists expressed initial apprehensions in their understanding of the process, they demonstrated enhanced confidence in their capacity to apply GRADE after completing workshop training and by acquiring experience. Panelists reiterated the importance of considering evidence-to-decision (EtD) criteria (ie, resources, feasibility, and cost-effectiveness) when adapting recommendations. The GDG encountered challenges with collecting local and regional data, prioritizing recommendations while considering intraregional diversity, and the lengthy publication period, although the latter stemmed from procedures not related to GRADE-ADOLOPMENT., Conclusions: GRADE-ADOLOPMENT is an important tool to facilitate the adaptation and uptake of clinical practice guidelines in novel settings. The GDG felt satisfied with their overall experience using the GRADE-ADOLOPMENT approach. However, their experience could have been optimized if they had access to robust regional evidence, more recommendations to adapt from, and worked with more efficient guideline production timelines., Competing Interests: Declaration of competing interest The authors have no conflict of interest to declare., (Copyright © 2024. Published by Elsevier Inc.)

The traditional healthcare model is focused on diseases (medicine and natural science) and does not acknowledge patients' resources and abilities to be experts in their own lives based on their lived experiences. Improving healthcare safety, quality, and coordination, as well as quality of life, is an important aim in the care of patients with chronic conditions. Person-centered care needs to ensure that people's values and preferences guide clinical decisions. This paper reviews current knowledge to develop (1) digital care pathways for rhinitis and asthma multimorbidity and (2) digitally enabled, person-centered care. 1 It combines all relevant research evidence, including the so-called real-world evidence, with the ultimate goal to develop digitally enabled, patient-centered care. The paper includes (1) Allergic Rhinitis and its Impact on Asthma (ARIA), a 2-decade journey, (2) Grading of Recommendations, Assessment, Development and Evaluation (GRADE), the evidence-based model of guidelines in airway diseases, (3) mHealth impact on airway diseases, (4) From guidelines to digital care pathways, (5) Embedding Planetary Health, (6) Novel classification of rhinitis and asthma, (7) Embedding real-life data with population-based studies, (8) The ARIA-EAACI (European Academy of Allergy and Clinical Immunology) strategy for the management of airway diseases using digital biomarkers, (9) Artificial intelligence, (10) The development of digitally enabled, ARIA person-centered care, and (11) The political agenda. The ultimate goal is to propose ARIA 2024 guidelines centered around the patient to make them more applicable and sustainable., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: To compare the efficacy of influenza vaccines of any valency for adults 60 years and older., Design and Setting: Systematic review with network meta-analysis (NMA) of randomised controlled trials (RCTs). MEDLINE, EMBASE, JBI Evidence-Based Practice (EBP) Database, PsycINFO, and Cochrane Evidence -Based Medicine database were searched from inception to 20 June 20, 2022. Two reviewers screened, abstracted, and appraised articles (Cochrane Risk of Bias (ROB) 2.0 tool) independently. We assessed certainty of findings using Confidence in Network Meta-Analysis and Grading of Recommendations, Assessment, Development and Evaluations approaches. We performed random-effects meta-analysis and network meta-analysis (NMA), and estimated odds ratios (ORs) for dichotomous outcomes and incidence rate ratios (IRRs) for count outcomes along with their corresponding 95% confidence intervals (CIs) and prediction intervals., Participants: Older adults (≥60 years old) receiving an influenza vaccine licensed in Canada or the USA (vs placebo, no vaccine, or any other licensed vaccine), at any dose., Main Outcome Measures: Laboratory-confirmed influenza (LCI) and influenza-like illness (ILI). Secondary outcomes were the number of vascular adverse events, hospitalisation for acute respiratory infection (ARI) and ILI, inpatient hospitalisation, emergency room (ER) visit for ILI, outpatient visit, and mortality, among others., Results: We included 41 RCTs and 15 companion reports comprising 8 vaccine types and 206 032 participants. Vaccines may prevent LCI compared with placebo, with high-dose trivalent inactivated influenza vaccine (IIV3-HD) (NMA: 9 RCTs, 52 202 participants, OR 0.23, 95% confidence interval (CI) (0.11 to 0.51), low certainty of evidence) and recombinant influenza vaccine (RIV) (OR 0.25, 95%CI (0.08 to 0.73), low certainty of evidence) among the most efficacious vaccines. Standard dose trivalent IIV3 (IIV3-SD) may prevent ILI compared with placebo, but the result was imprecise (meta-analysis: 2 RCTs, 854 participants, OR 0.39, 95%CI (0.15 to 1.02), low certainty of evidence). Any HD was associated with prevention of ILI compared with placebo (NMA: 9 RCTs, 65 658 participants, OR 0.38, 95%CI (0.15 to 0.93)). Adjuvanted quadrivalent IIV (IIV4-Adj) may be associated with the least vascular adverse events, but the results were very uncertain (NMA: eight 8 RCTs, 57 677 participants, IRR 0.18, 95%CI (0.07 to 0.43), very low certainty of evidence). RIV on all-cause mortality may be comparable to placebo (NMA: 20 RCTs, 140 577 participants, OR 1.01, 95%CI (0.23 to 4.49), low certainty of evidence)., Conclusions: This systematic review demonstrated efficacy associated with IIV3-HD and RIV vaccines in protecting older persons against LCI. RIV vaccine may reduce all-cause mortality when compared with other vaccines, but the evidence is uncertain. Differences in efficacy between influenza vaccines remain uncertain with very low to moderate certainty of evidence., Prospero Registration Number: CRD42020177357., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

There is insufficient evidence regarding the comparative efficacy and safety of pharmacological treatments of allergic rhinitis (AR). In the context of informing the 2024 revision of the Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines, we plan to perform three systematic reviews of randomized controlled trials (RCTs) comparing the desirable and undesirable effects (i) between intranasal and oral medications for AR; (ii) between combinations of intranasal and oral medications versus nasal or oral medications alone; and (iii) among different intranasal specific medications. We will search four electronic bibliographic databases and three clinical trials databases for RCTs examining patients ≥ 12 years old with seasonal or perennial AR. Assessed outcomes will include the Total Nasal Symptom Score, the Total Ocular Symptom Score, and the Rhinoconjunctivitis Quality-of-Life Questionnaire. We will assess the methodological quality of included primary studies by using the Cochrane risk-of-bias tool. If appropriate, we will perform a pairwise random-effects meta-analysis for each pair of assessed medication classes and outcomes, as well as a network meta-analysis to assess the comparative efficacy of intranasal medications among each other. Heterogeneity will be explored by sensitivity and subgroup analyses. This set of systematic reviews will allow for a comprehensive assessment of the effectiveness and safety of pharmacological interventions for AR and inform recommendations in the context of the ARIA guidelines., Competing Interests: LK reports grants from Allergopharma, MEDA/Mylan, ALK Abelló, LETI Pharma, Stallergenes, Sanofi, ASIT biotech, Lofarma Quintiles, AstraZeneca, GSK and Inmunotk, and personal fees from Allergopharma, MEDA/Mylan, HAL Allergie, LETI Pharma, Sanofi, Allergy Therapeut and Cassella Med, outside the submitted work. JAF reports grants from Astrazeneca and Mundipharma; and personal fees from AstraZeneca, Mundipharma, Sanofi, GSK and Teva, outside the submitted work. TZ reports grants from Novartis and Henkel; personal fees from Bayer Health Care, FAES, Novartis, Henkel, AstraZeneca, AbbVie, ALK, Almirall, Astellas, Bencard, Berlin Chemie, HAL, Leti, Meda, Menarini, Merck, MSD, Pfizer, Sanofi, Stallergenes, Takeda, Teva, UCB, Kryolan and L’Oréal, outside the submitted work. JB reports personal fees from Chiesi, Cipla, Hikma, Menarini, Mundipharma, Mylan, Novartis, Purina, Sanofi-Aventis, Takeda, Teva and Noucor and other from Kyomed-Innov, outside the submitted work., (© Dustri-Verlag Dr. K. Feistle.)

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., (© 2024 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Recommendations for or against the use of interventions need to consider both desirable and undesirable effects as well as patients' values and preferences (V&P). In the decision-making context, patients' V&P represent the relative importance people place on the outcomes resulting from a decision. Therefore, the balance between desirable and undesirable effects from an intervention should depend not only on the difference between benefits and harms but also on the value that patients place on them. V&P are therefore one of the criteria to be considered when formulating guideline recommendations in the Evidence-to-Decision framework developed by the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) Working Group. Patients' V&P may be quantified through utilities, which can be elicited using direct methods (e.g., standard gamble or time trade-off) or indirect methods (using validated instruments to measure health-related quality of life, such as EQ-5D). The GRADE approach recommends conducting systematic reviews to summarise all the available evidence and assess the degree of certainty on V&P. In this article, we discuss the importance of considering patients' V&P and provide examples of how they are considered in the 2024 person-centred Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines., (© 2024 The Author(s). Clinical and Translational Allergy published by John Wiley & Sons Ltd on behalf of European Academy of Allergy and Clinical Immunology.)

Background: The transitivity assumption is the cornerstone of network meta-analysis (NMA). Violating transitivity compromises the credibility of the indirect estimates and, by extent, the estimated treatment effects of the comparisons in the network. The present study offers comprehensive empirical evidence on the completeness of reporting and evaluating transitivity in systematic reviews with multiple interventions., Methods: We screened the datasets of two previous empirical studies, resulting in 361 systematic reviews with NMA published between January 2011 and April 2015. We updated our evidence base with an additional 360 systematic reviews with NMA published between 2016 and 2021, employing a pragmatic approach. We devised assessment criteria for reporting and evaluating transitivity using relevant methodological literature and compared their reporting frequency before and after the PRISMA-NMA statement., Results: Systematic reviews published after PRISMA-NMA were more likely to provide a protocol (odds ratio (OR): 3.94, 95% CI: 2.79-5.64), pre-plan the transitivity evaluation (OR: 3.01, 95% CI: 1.54-6.23), and report the evaluation and results (OR: 2.10, 95% CI: 1.55-2.86) than those before PRISMA-NMA. However, systematic reviews after PRISMA-NMA were less likely to define transitivity (OR: 0.57, 95% CI: 0.42-0.79) and discuss the implications of transitivity (OR: 0.48, 95% CI: 0.27-0.85) than those published before PRISMA-NMA. Most systematic reviews evaluated transitivity statistically than conceptually (40% versus 12% before PRISMA-NMA, and 54% versus 11% after PRISMA-NMA), with consistency evaluation being the most preferred (34% before versus 47% after PRISMA-NMA). One in five reviews inferred the plausibility of the transitivity (22% before versus 18% after PRISMA-NMA), followed by 11% of reviews that found it difficult to judge transitivity due to insufficient data. In justifying their conclusions, reviews considered mostly the comparability of the trials (24% before versus 30% after PRISMA-NMA), followed by the consistency evaluation (23% before versus 16% after PRISMA-NMA)., Conclusions: Overall, there has been a slight improvement in reporting and evaluating transitivity since releasing PRISMA-NMA, particularly in items related to the systematic review report. Nevertheless, there has been limited attention to pre-planning the transitivity evaluation and low awareness of the conceptual evaluation methods that align with the nature of the assumption., (© 2024. The Author(s).)

Background and Aims: Single-operator cholangioscopy (SOC) offer a diagnostic and therapeutic alternative with an improved optical resolution over conventional techniques; however, there are no standardized clinical practice guidelines for this technology. This evidence-based guideline from the Colombian Association of Digestive Endoscopy (ACED) intends to support patients, clinicians, and others in decisions about using in adults the SOC compared to endoscopic retrograde cholangiopancreatography (ERCP), to diagnose indeterminate biliary stricture and to manage difficult biliary stones., Methods: ACED created a multidisciplinary guideline panel balanced to minimize potential bias from conflicts of interest. Universidad de los Andes and the Colombia Grading of Recommendations Assessment, Development and Evaluation (GRADE) Network supported the guideline-development process, updating and performing systematic evidence reviews. The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients. The GRADE approach was used, including GRADE Evidence-to-Decision frameworks., Results: The panel agreed on one recommendation for adult patients with indeterminate biliary strictures and one for adult patients with difficult biliary stones when comparing SOC versus ERCP., Conclusion: For adult patients with indeterminate biliary strictures, the panel made a conditional recommendation for SOC with stricture pattern characterization over ERCP with brushing and/or biopsy for sensitivity, specificity, and procedure success rate outcomes. For the adult patients with difficult biliary stones the panel made conditional recommendation for SOC over ERCP with large-balloon dilation of papilla. Additional research is required on economic estimations of SOC and knowledge translation evaluations to implement SOC intervention in local contexts., (© 2023. The Author(s).)

We carried out a systematic review and meta-analysis to determine the effectiveness and safety of non-invasive electrical stimulation (NES) for vision restoration. We systematically searched for randomised controlled trials (RCTs) comparing NES with sham stimulation, for vision restoration between 2000 and 2022 in CENTRAL, MEDLINE, EMBASE, and LILACS. The main outcomes were as follows: visual acuity (VA); detection accuracy; foveal threshold; mean sensitivity as the parameter for the visual field; reading performance; contrast sensitivity (CS); electroencephalogram; quality of life (QoL), and safety. Two reviewers independently selected studies, extracted data, and evaluated the risk of bias using the Cochrane risk of bias 2.0 tool. The certainty in the evidence was determined using the GRADE framework. Protocol registration: CRD42022329342. Thirteen RCTs involving 441 patients with vision impairment indicate that NES may improve VA in the immediate post-intervention period (mean difference [MD] = -0.02 logMAR, 95% confidence intervals [CI] -0.08 to 0.04; low certainty), and probably increases QoL and detection accuracy (MD = 0.08, 95% CI -0.25 to 0.42 and standardised MD [SMD] = 0.09, 95% CI -0.58 to 0.77, respectively; both moderate certainty). NES likely results in little or no difference in mean sensitivity (SMD = -0.03, 95% CI -0.53 to 0.48). Compared with sham stimulation, NES increases the risk of minor adverse effects (risk ratio = 1.24, 95% CI 0.99 to 1.54; moderate certainty). The effect of NES on CS, reading performance, and electroencephalogram was uncertain. Our study suggests that although NES may slightly improve VA, detection accuracy, and QoL, the clinical relevance of these findings remains uncertain. Future research should focus on improving the available evidence's precision and consistency., Competing Interests: No potential conflict of interest was reported by the authors., (© 2023 Taylor & Francis Group, LLC.)

Background: Atopic dermatitis (AD) is a common skin condition with multiple topical treatment options, but uncertain comparative effects., Objective: We sought to systematically synthesize the benefits and harms of AD prescription topical treatments., Methods: For the 2023 American Academy of Allergy, Asthma & Immunology and American College of Allergy, Asthma, and Immunology Joint Task Force on Practice Parameters AD guidelines, we searched MEDLINE, EMBASE, CENTRAL, CINAHL, LILACS, ICTRP, and GREAT databases to September 5, 2022, for randomized trials addressing AD topical treatments. Paired reviewers independently screened records, extracted data, and assessed risk of bias. Random-effects network meta-analyses addressed AD severity, itch, sleep, AD-related quality of life, flares, and harms. The Grading of Recommendations Assessment, Development and Evaluation approach informed certainty of evidence ratings. We classified topical corticosteroids (TCS) using 7 groups-group 1 being most potent. This review is registered in the Open Science Framework (https://osf.io/q5m6s)., Results: The 219 included trials (43,123 patients) evaluated 68 interventions. With high-certainty evidence, pimecrolimus improved 6 of 7 outcomes-among the best for 2; high-dose tacrolimus (0.1%) improved 5-among the best for 2; low-dose tacrolimus (0.03%) improved 5-among the best for 1. With moderate- to high-certainty evidence, group 5 TCS improved 6-among the best for 3; group 4 TCS and delgocitinib improved 4-among the best for 2; ruxolitinib improved 4-among the best for 1; group 1 TCS improved 3-among the best for 2. These interventions did not increase harm. Crisaborole and difamilast were intermediately effective, but with uncertain harm. Topical antibiotics alone or in combination may be among the least effective. To maintain AD control, group 5 TCS were among the most effective, followed by tacrolimus and pimecrolimus., Conclusions: For individuals with AD, pimecrolimus, tacrolimus, and moderate-potency TCS are among the most effective in improving and maintaining multiple AD outcomes. Topical antibiotics may be among the least effective., (Copyright © 2023. Published by Elsevier Inc.)

This practice guideline was developed by the chronic kidney disease (CKD) Task Force, which was composed of clinical and methodological experts. The Saudi Arabian Ministry of Health and its health holding company commissioned this guideline project to support the realization of Vision 2030's health-care transformation pillar. The synthesis of these guidelines was guided by the Grading of Recommendations Assessment, Development, and Evaluation (GRADE)- ADOLOPMENT methodology. The final guidelines addressed 12 clinical questions on the management of blood pressure in patients with CKD through a set of recommen-dations and performance measures. The recom-mendations included antihypertensive agents in children; renin- angiotensin system inhibition (RASi) versus non-RASi in adults; intensive versus standard blood pressure targets; early versus late assessment for kidney replacement therapy (KRT); late versus early preparation strategies for KRT; CKD symptoms during assessment for KRT or conservative manage-ment; initiation of KRT in patients with deteriorating CKD; choice of KRT modality or conservative management in certain CKD patient groups; changing or discontinuing KRT modalities; the frequency of reviews for KRT or conservative management; and information, education, and support. These conditional recommendations were based on a low to very low certainty of evidence, which highlights the need for high-quality randomized trials com-paring different antihypertensive agents in patients with CKD., (Copyright © 2023 Copyright: © 2023 Saudi Journal of Kidney Diseases and Transplantation.)

Objective: To identify and assess the effect of community-based Knowledge Translation Strategies (KTS) on maternal, neonatal, and perinatal outcomes. Methods: We conducted systematic searches in Medline, Embase, CENTRAL, CINAHL, PsycInfo, LILACS, Wholis, Web of Science, ERIC, Jstor, and Epistemonikos. We assessed the certainty of the evidence of the studies using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework. Results: We identified seven quantitative and seven qualitative studies. Quantitative findings suggest that there is a possible effect on reducing maternal mortality (RR 0.65; 95% CI, 0.48-0.87; moderate evidence certainty); neonatal mortality (RR 0.79; 95% CI 0.70-0.90; moderate evidence certainty); and perinatal mortality (RR 0.84; 95% CI 0.77-0.91; moderate evidence certainty) in women exposed to KTS compared to those who received conventional interventions or no intervention at all. Analysis of qualitative studies identified elements that allowed to generate benefit effects in improving maternal, neonatal, and perinatal outcomes. Conclusion: The KTS in maternal, neonatal, and perinatal outcomes might encourage the autonomy of communities despite that the certainty of evidence was moderate., Competing Interests: The authors declare that they do not have any conflicts of interest., (Copyright © 2023 Montoya-Sanabria, Hernández-Sandoval, Cáceres-Maldonado, Díaz-Barrero, Zapata-Matheus, Mejia-Pérez, De La Torre-Arias, Caballero-Diaz, González-Uribe, Domínguez-Torres, Nguyen and Yepes-Nuñez.)

Objectives: To evaluate alternative formats of summary of findings (SoF) tables for single comparison with multiple outcomes., Study Design and Setting: We conducted a three-arm randomized controlled noninferiority trial (RCT) in the following systematic review (SR) users: researchers, clinical practice guideline developers, health care providers, policymakers, and knowledge transfer organizations to measure understanding, accessibility, satisfaction, and preference across the current grading of recommendations assessment, development, and evaluation (GRADE) SoF, an alternative GRADE SoF, or an adapted evidence-based practice center (EPC) program SoF table., Results: One Hundred Seventy-Nine participants were randomized, and 129 participants completed the RCT (n = 47 current GRADE, n = 41 alternative GRADE, n = 41 adapted EPC). Understanding the certainty of evidence and treatment effect was comparable across groups. The adapted EPC SoF table was inferior for quantifying risk and RD compared to the alternatives (<35% correct vs. >85% correct). Participants reported increased satisfaction when SoF tables presented number needed to treat (NNT), anticipated absolute effect differences, and narrative syntheses for evidence that could not be meta-analyzed. Participants reported accessibility to information as significantly better in both GRADE SoF tables, when compared with the adapted EPC SoF table. Participants preferred the alternative GRADE SoF table format., Conclusion: The alternative GRADE SoF table is a promising format for SR users preferring a comprehensive presentation of SR results for single comparisons., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Atopic dermatitis (AD, eczema) is driven by a combination of skin barrier defects, immune dysregulation, and extrinsic stimuli such as allergens, irritants, and microbes. The role of environmental allergens (aeroallergens) in triggering AD remains unclear., Objective: We systematically synthesized evidence regarding the benefits and harms of allergen immunotherapy (AIT) for AD., Methods: As part of the 2022 American Academy of Allergy, Asthma & Immunology/American College of Allergy, Asthma and Immunology Joint Task Force on Practice Parameters AD Guideline update, we searched the MEDLINE, EMBASE, CENTRAL, CINAHL, LILACS, Global Resource for Eczema Trials, and Web of Science databases from inception to December 2021 for randomized controlled trials comparing subcutaneous immunotherapy (SCIT), sublingual immunotherapy (SLIT), and/or no AIT (placebo or standard care) for guideline panel-defined patient-important outcomes: AD severity, itch, AD-related quality of life (QoL), flares, and adverse events. Raters independently screened, extracted data, and assessed risk of bias in duplicate. We synthesized intervention effects using frequentist and Bayesian random-effects models. The GRADE approach determined the quality of evidence., Results: Twenty-three randomized controlled trials including 1957 adult and pediatric patients sensitized primarily to house dust mite showed that add-on SCIT and SLIT have similar relative and absolute effects and likely result in important improvements in AD severity, defined as a 50% reduction in SCORing Atopic Dermatitis (risk ratio [95% confidence interval] 1.53 [1.31-1.78]; 26% vs 40%, absolute difference 14%) and QoL, defined as an improvement in Dermatology Life Quality Index by 4 points or more (risk ratio [95% confidence interval] 1.44 [1.03-2.01]; 39% vs 56%, absolute difference 17%; both outcomes moderate certainty). Both routes of AIT increased adverse events (risk ratio [95% confidence interval] 1.61 [1.44-1.79]; 66% with SCIT vs 41% with placebo; 13% with SLIT vs 8% with placebo; high certainty). AIT's effect on sleep disturbance and eczema flares was very uncertain. Subgroup and sensitivity analyses were consistent with the main findings., Conclusions: SCIT and SLIT to aeroallergens, particularly house dust mite, can similarly and importantly improve AD severity and QoL. SCIT increases adverse effects more than SLIT. These findings support a multidisciplinary and shared decision-making approach to optimally managing AD., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: The aim of this study is to identify and describe the processes suggested for the formulation of healthcare recommendations in healthcare guidelines available in guidance documents., Methods: We searched international databases in May 2020 to retrieve guidance documents published by organizations dedicated to guideline development. Pairs of researchers independently selected and extracted data about the characteristics of the guidance document, including explicit or implicit recommendation-related criteria and processes considered, as well as the use of evidence to decision (EtD) frameworks., Results: We included 68 guidance documents. Most organizations reported a system for grading the strength of recommendations (88%), half of them being the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach. Two out of three guidance documents (66%) proposed the use of a framework to guide the EtD process. The GRADE-EtD framework was the most often reported framework (19 organizations, 42%), whereas 20 organizations (44%) proposed their own multicriteria frameworks. Using any EtD framework was related with a more comprehensive set of recommendation-related criteria compared to no framework, especially for criteria like values, equity, and acceptability., Conclusion: Although limited, the use of EtD frameworks was associated with the inclusion of relevant recommendation criteria. Among the EtD structured frameworks, the GRADE-EtD framework offers the most comprehensive perspective for evidence-informed decision-making processes., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: The use of respiratory devices can mitigate the spread of diseases such as COVID-19 in community settings. We aimed to determine the effectiveness of closed face shields with surgical face masks to prevent SARS-CoV-2 transmission in working adults during the COVID-19 pandemic in Bogotá, Colombia., Methods: An open-label non-inferiority randomized controlled trial that randomly assigned participants to one of two groups: the intervention group was instructed to wear closed face shields with surgical face masks, and the active control group was instructed to wear only surgical face masks. The primary outcome was a positive reverse transcription polymerase chain reaction test, IgG/IgM antibody test for SARS-CoV-2 detection, or both during and at the end of the follow-up period of 21 days. The non-inferiority limit was established at - 5%., Results: A total of 316 participants were randomized, 160 participants were assigned to the intervention group and 156 to the active control group. In total, 141 (88.1%) participants in the intervention group and 142 (91.0%) in the active control group completed the follow-up., Primary Outcome: a positive SARS-CoV-2 test result was identified in one (0.71%) participant in the intervention group and three (2.1%) in the active control group. In the intention-to-treat analysis, the absolute risk difference was - 1.40% (95% CI [- 4.14%, 1.33%]), and in the per-protocol analysis, the risk difference was - 1.40% (95% CI [- 4.20, 1.40]), indicating non-inferiority of the closed face shield plus face mask (did not cross the non-inferiority limit)., Conclusions: The use of closed face shields and surgical face masks was non-inferior to the surgical face mask alone in the prevention of SARS-CoV-2 infection in highly exposed groups. Settings with highly active viral transmission and conditions such as poor ventilation, crowding, and high mobility due to occupation may benefit from the combined use of masks and closed face shields to mitigate SARS-CoV-2 transmission., Trial Registration: ClinicalTrials.gov NCT04647305 . Registered on November 30, 2020., (© 2022. The Author(s).)

Background: Prognostic factors in lung transplantation are those variables that are associated with transplant outcomes. Knowledge of donor and recipient prognostic variables can aid in the optimal allocation of donor lungs to transplant recipients and can also inform post-operative discussions with patients about prognosis. Current research findings related to prognostic factors in lung transplantation are inconsistent and the relative importance of various factors is unclear. This review aims to provide the best possible estimates of the association between putative prognostic variables and 1-year all-cause mortality in adult lung transplant recipients., Methods: We searched 5 bibliographic databases for studies assessing the associations between putative predictors (related to lung donors, recipients, or the transplant procedure) and 1-year recipient mortality. We pooled data across studies when justified and utilized GRADE methodology to assess the certainty in the evidence., Results: From 72 eligible studies (2002-2020), there were 34 recipient variables, 4 donor variables, 10 procedural variables, and 7 post-transplant complication variables that were amenable to a meta-analysis. With a high degree of certainty in the evidence only post-transplant need for extra-corporeal membrane oxygenation (ECMO) (HR 1.91, 95% CI 1.79-2.04) predicted 1-year mortality. No donor variables appeared to predict transplant outcome with high or even moderate certainty., Conclusion: Across the range of contemporary donors and recipients that clinicians accept for lung transplantation, this review, with high certainty, found 1 prognostic factor that predicted 1-year mortality, and 37 additional factors with a moderate degree of certainty. The lack of prognostic significance for some widely accepted factors (e.g., donor smoking, age) likely relates to existing limits in the range of these variables at the time of donor and recipient selection., (Copyright © 2022 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Objectives: We conceptualize patient values and preferences as the relative importance of health outcomes (RIO) which are often obtained through utility elicitation research. A transparent and structured approach to present synthesized RIO evidence and the certainty of this evidence is needed. This study aims to adapt the summary of findings (SoF) table to describe the RIO., Study Design and Setting: We performed three interactive workshops with a protype version of the SoF table for RIO, evidence adapted from the SoF table for intervention effects. We then tested the new format through semi-structured interviews with professionals who interpret RIO evidence (e.g., systematic review authors and guideline developers)., Results: We adapted the SoF table for the presentation of RIO evidence. This SoF table may be easy to use, but bears one risk: some participants misunderstood the utility information and the variability around the RIO. We added a visual analogue scale to clarify the concept of utilities., Conclusion: Through a multi-stage process including brainstorming sessions and interviews, we adapted the SoF table to present RIO evidence. This table may enhance understanding of evidence synthesis of values and preferences, facilitating the incorporation of this type of evidence in decision-making., (Copyright © 2022. Published by Elsevier Inc.)

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., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: An instrument to assess Allergic Rhinitis (AR) Health-Related Quality of Life (HRQL) in adult patients was developed in Spain. No validated instrument is currently cross-culturally adapted for use in daily practice to assess HRQL in AR patients in Colombia., Purpose: The aim of this study was to evaluate the measurement performance of an AR-HRQL specific questionnaire, ESPRINT-15 (Cuestionario ESPañol de Calidad de Vida en RINiTis), in Colombian adult patients with AR using the Classic Test Theory (CTT) and the Generalizability theory (G-theory) frameworks., Methods: We conducted the cross-cultural adaptation in 2 stages. In stage 1, we evaluated comprehensibility, acceptability, and feasibility of ESPRINT-15 in healthy adults and adult patients with AR. In stage 2, we examined both reliability and validity of ESPRINT-15 scores using CTT and overall reliability applying the G-theory in adult patients with AR., Results: For feasibility and acceptability, all items showed a higher than 95% level of understanding, and modifications in the original questionnaire were unnecessary. Reliability and validity using CTT showed a high internal consistency (Cronbach's alpha and Mc McDonald's omega = 0.95) and test-retest reliability (scores from 0.70 to 0.76). The overall reliability score using G-theory was 0.75, and G-coefficients scores associated with internal consistency and test-retest reliability measures were 0.96 and 0.61, respectively. Validity using exploratory factor analysis (EFA) identified 2 factors instead of the original ESPRINT-15 4 domains. However, confirmatory factor analysis (CFA) showed good fit regarding the original model., Conclusions: The proposed cross-cultural adaptation of ESPRINT-15 showed good reliability and validity measures. Additionally, it was easy to use and administer. ESPRINT-15 can be used clinically and for research in Colombian adults' patients with AR. CTT and the G-theory can be used in epidemiological studies to adapt AR-HRQL questionnaires cross-culturally in adult patients with AR., Competing Interests: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper., (© 2021 The Author(s).)

Background: The coronavirus disease 19 (covid-19) pandemic has underscored the need to expedite clinical research, which may lead investigators to shift away from measuring patient-important outcomes (PIO), limiting research applicability. We aim to investigate if randomized controlled trials (RCTs) of covid-19 pharmacological therapies include PIOs., Methods: We will perform a meta-epidemiological study of RCTs that included people at risk for, or with suspected, probable, or confirmed covid-19, examining any pharmacological treatment or blood product aimed at prophylaxis or treatment. We will obtain data from all RCTs identified in a living network metanalysis (NMA). The main data sources are the living WHO covid-19 database up to 1 March 2021 and six additional Chinese databases up to 20 February 2021. Two reviewers independently will review each citation, full-text article, and abstract data. To categorize the outcomes according to their importance to patients, we will adapt a previously defined hierarchy: a) mortality, b) quality of life/ functional status/symptoms, c) morbidity, and d) surrogate outcomes. Outcomes within the category a) and b) will be considered critically important to patients, and outcomes within the category c) will be regarded as important. We will use descriptive statistics to assess the proportion of studies that report each category of outcomes. We will perform univariable and multivariable analysis to explore associations between trial characteristics and the likelihood of reporting PIOs., Discussion: The findings from this meta-epidemiological study will help health care professionals and researchers understand if the current covid-19 trials are effectively assessing and reporting the outcomes that are important to patients. If a deficiency in capturing PIOs is identified, this information may help inform the development of future RCTs in covid-19., Systematic Review Registrations: Open Science Framework registration: osf.io/6xgjz ., (© 2021. The Author(s).)

Background: Vitamin D has been widely promoted for bone health through supplementation and fortification of the general adult population. However, there is growing evidence that does not support these strategies. Our aim is to review the quality and recommendations on vitamin D nutritional and clinical practice guidelines and to explore predictive factors for their direction and strength., Methods: We searched three databases and two guideline repositories from 2010 onwards. We performed a descriptive analysis, a quality appraisal using AGREE II scores (Appraisal of Guidelines Research and Evaluation) and a bivariate analysis evaluating the association between direction and strength of recommendations, AGREE II domains' scores and pre-specified characteristics., Results: We included 34 guidelines, 44.1% recommended, 26.5% suggested and 29.4% did not recommend vitamin D supplementation. Guidelines that scored higher for "editorial independence" and "overall quality score" were less likely to recommend or suggest vitamin D supplementation (median 68.8 vs 35.4; P = .001 and 58.3 vs 37.5; P = .02). Guidance produced by government organisations and those that reported source of funding were associated with higher AGREE II scores. Unclear role of source of funding was associated with recommending or suggesting vitamin D supplementation (P = .034). Editorial independence was an independent predictor for recommending or suggesting vitamin D supplementation (OR 1.09; CI95% 1.02 to 1.16; P = .006)., Conclusions: Policymakers, clinicians and patients should be aware that lower quality guidelines and those reporting conflicts of interest are more likely to promote vitamin D supplementation. Guideline organisations should improve the quality of their recommendations' development and the management of conflicts of interest. Users and editors should be aware of these findings when using and appraising guidelines., (© 2021 John Wiley & Sons Ltd.)

Objective: To describe the characteristics of Covid-19 randomized clinical trials (RCTs) and examine the association between trial characteristics and the likelihood of finding a significant effect., Study Design: We conducted a systematic review to identify RCTs (up to October 21, 2020) evaluating drugs or blood products to treat or prevent Covid-19. We extracted trial characteristics (number of centers, funding sources, and sample size) and assessed risk of bias (RoB) using the Cochrane RoB 2.0 tool. We performed logistic regressions to evaluate the association between RoB due to randomization, single vs. multicentre, funding source, and sample size, and finding a statistically significant effect., Results: We included 91 RCTs (n = 46,802); 40 (44%) were single-center, 23 (25.3%) enrolled <50 patients, 28 (30.8%) received industry funding, and 75 (82.4%) had high or probably high RoB. Thirty-eight trials (41.8%) reported a statistically significant effect. RoB due to randomization and being a single-center trial were associated with increased odds of finding a statistically significant effect., Conclusions: There is high variability in RoB among Covid-19 trials. Researchers, funders, and knowledge-users should be cognizant of the impact of RoB due to randomization and single-center trial status in designing, evaluating, and interpreting the results of RCTs., Registration: CRD42020192095., (Copyright © 2021. Published by Elsevier Inc.)

Background and Objective: Guideline development groups or other health care decision makers frequently encounter situations that require a simultaneous comparison of multiple interventions. This sometimes becomes apparent either when they identify questions of interest, before they formulate recommendations, or it may surface only when recommendations have already been formulated based on pairwise comparisons., Methods: Using examples from the World Health Organization, the European Commission, and a professional society, we developed a flexible approach to developing recommendations when a multiple-intervention comparison (MC) is needed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) evidence to decision (EtD) frameworks. We iteratively refined this approach through user testing and then included a module in GRADE's official software GRADEpro to test the approach in two real and one theoretical guideline recommendations., Results: We found the approach feasible and that all EtD criteria should be considered in an MC approach. We judged that guideline development groups and other decision makers will benefit from the availability of a network meta-analyses (NMA) of intervention effects to support decisions; however, NMA supports only one of many criteria, that is, the balance of health benefits and harms, and is therefore helpful, but not essential to the approach we propose. When similar but not identical comparators are used to address MC, challenges may arise with intransitivity and the relative rankings of interventions., Conclusion: We successfully applied the MC approach and software module in generating recommendations across different scenarios and identified challenges. The MC approach allows guideline groups and other decision makers to transparently and critically assess multiple options for a given health question. Application of the approach by others may lead to refinement and allow for better understanding of its impact in developing recommendations and making choices., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Guideline recommendations may be affected by flaws in the process, inappropriate panel member selection or conduct, conflicts of interest and other factors. To our knowledge, no validated tool exists to evaluate guideline development from the perspective of those directly involved in the process. Our objective was to develop and validate a universal tool, the PANELVIEW instrument, to assess guideline processes, methods and outcomes from the perspective of the participating guideline panellists and group members., Methods: We performed a systematic literature search and surveys of guideline groups (identified through contacting international organizations and convenience sampling of working panels) to inform item generation. Subsequent groups of guideline methodologists and panellists reviewed items for face validity and missing items. We used surveys, interviews and expert review for item reduction and phrasing. For reliability assessment and feedback, we tested the PANELVIEW tool in 8 international guideline groups., Results: We surveyed 62 members from 13 guideline panels, contacted 19 organizations and reviewed 20 source documents to generate items. Fifty-three additional key informants provided feedback about phrasing of the items and response options. We reduced the number of items from 95 to 34 across domains that included administration, training, conflict of interest, group dynamics, chairing, evidence synthesis, formulating recommendations and publication. The tool takes about 10 minutes to complete and showed acceptable measurement properties., Interpretation: The PANELVIEW instrument fills a gap by enabling guideline organizations to involve clinicians, patients and other participants in evaluating their guideline processes. The tool can inform quality improvement of existing or new guideline programs, focusing on insight into and transparency of the guideline development process, methods and outcomes., Competing Interests: Competing interests: Authors of this manuscript have been involved in the development of various guideline manuals that are referenced in this article. Wojtek Wiercioch, Elie Akl and Holger Schünemann will retain copyright of the PANELVIEW tool through McMaster University (Technology ID 20-031), and the tool may be licensed in the future. Maicon Falavigna received consulting fees from Novartis, AbbVie, Roche, Boehringer Ingelheim, PTC Therapeutics and Sanofi Genzyme, unrelated to the submitted work. No other competing interests were declared., (© 2020 Joule Inc. or its licensors.)

Background: Atopic dermatitis (AD) is an inflammatory chronic condition that affects the skin of children and adults and has an important impact on the quality of life. Treatments for AD are based on environmental controls, topical and systemic therapies, and allergen-specific immunotherapy (AIT). However, it remains unclear the effectiveness and adverse events of AIT and all conventional topical treatments compared with placebo and each other for AD., Methods: We will search five electronic databases [Central Cochrane register of controlled trials (CENTRAL), MEDLINE, EMBASE, CINAHL, and LILACS] from inception until November 2019 with no language restriction, and we will include experimental studies [randomized controlled trials (RCTs), and quasi-RCTs]. The primary outcome is global and specific skin symptoms assessment. Secondary outcomes are hospital length of stay, quality of life, and adverse events. Reviewers independently will extract data from the studies that meet our inclusion criteria and will assess the risk of bias of individual primary studies. We will conduct random effects pairwise meta-analyses for the observed pairwise comparisons with at least two trials. Then, we will perform random-effects Bayesian network meta-analysis (NMA) to obtain treatment effects for all possible comparisons and to provide a hierarchy of all interventions for each outcome. Possible incoherence between direct and indirect sources of evidence will be investigated locally (if possible) and globally. To investigate sources of statistical heterogeneity, we will perform a series of meta-regression analyses based on pre-specified important effect modifiers. Two authors will appraise the certainty of the evidence for each outcome applying the GRADE's framework for NMA., Discussion: The findings of this systematic review will shed the light on the effectiveness and adverse events of all possible comparisons for treating AD and on the quality of the collated evidence for recommendations. It will also provide critical information to health care professionals to comprehend and manage this disease at different age stages, treatment type, duration, and severity of atopic dermatitis., Systematic Review Registration: PROSPERO Protocol ID CRD42019147106.

The impact of pharmacologic prophylaxis for venous thromboembolism in patients undergoing neurosurgical intervention remains uncertain. We reviewed the efficacy and safety of pharmacologic compared with nonpharmacologic thromboprophylaxis in neurosurgical patients. Three databases were searched through April 2018, including those for randomized controlled trials (RCTs) and for nonrandomized controlled studies (NRSs). Independent reviewers assessed the certainty of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Seven RCTs and 3 NRSs proved eligible. No studies reported on symptomatic proximal and distal deep vein thrombosis (DVT). Two RCTs reported on screening-detected proximal and distal DVTs. We used the findings of these 2 RCTs as the closest surrogate outcomes to inform the proximal and distal DVT outcomes. These 2 RCTs suggest that pharmacologic thromboprophylaxis may decrease the risk of developing asymptomatic proximal DVT (relative risk [RR], 0.50; 95% confidence interval [CI], 0.30-0.84; low certainty). Findings were uncertain for mortality (RR, 1.27; 95% CI, 0.57-2.86; low certainty), symptomatic pulmonary embolism (PE) (RR, 0.84; 95% CI, 0.03-27.42; very low certainty), asymptomatic distal DVT (RR, 0.54; 95% CI, 0.27-1.08; very low certainty), and reoperation (RR, 0.43; 95% CI, 0.06-2.84; very low certainty) outcomes. NRSs also reported uncertain findings for whether pharmacologic prophylaxis affects mortality (RR, 0.72; 95% CI, 0.46-1.13; low certainty) and PE (RR, 0.18; 95% CI, 0.01-3.76). For risk of bleeding, findings were uncertain in both RCTs (RR, 1.57; 95% CI, 0.70-3.50; low certainty) and NRSs (RR, 1.45; 95% CI, 0.30-7.12; very low certainty). In patients undergoing neurosurgical procedures, low certainty of evidence suggests that pharmacologic thromboprophylaxis confers benefit for preventing asymptomatic (screening-detected) proximal DVT with very low certainty regarding its impact on patient-important outcomes.

The goal of this systematic review and network meta-analysis was to compare the relative effects of toothpaste formulations for dentin hypersensitivity (DH), tested in randomized controlled trials (RCTs). We searched 7 databases to February 2019. Paired reviewers independently screened studies, extracted data, and performed risk of bias assessment. The outcome of interest was painful response measured through tactile, cold, and air stimuli. We conducted a random-effects Bayesian network meta-analysis using standardized mean difference (SMD) and their credible intervals (CIs) as the measure of effect for each pain stimuli. We assessed certainty of evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. We included 125 RCTs (12,541 patients). For tactile stimulus, the following active ingredients showed large beneficial effects compared to fluoride with moderate certainty of evidence (SMD; 95% CI): potassium + stannous fluoride (SnF 2 ) (3.05; 1.69-4.41), calcium sodium phosphosilicate (CSP) (2.14; 0.75-3.53), SnF 2 (2.02; 1.06-2.99), potassium + hydroxyapatite (2.47; 0.3-4.64), strontium (1.43; 0.46-2.41), and potassium (1.23; 0.48-1.98). For cold stimulus, CSP showed large beneficial effects compared to fluoride (3.93; 0.34-7.53) with moderate certainty; for air stimulus, arginine (2.22; 1.45-2.99), potassium + hydroxyapatite (2.44; 0.33-4.55), potassium + SnF 2 (2.28; 0.87-3.69), CSP (1.98; 0.99-2.98), and SnF 2 (1.9; 1.03-2.77) showed large beneficial effects compared to fluoride with moderate to high certainty. Most toothpaste formulations showed evidence of superiority against placebo or fluorides (amine fluoride, sodium monofluorophosphate, or sodium fluoride). CSP was most beneficial for all 3 stimuli with high to moderate certainty. SnF 2 alone and potassium combined with SnF 2 or hydroxyapatite were beneficial for tactile and air stimulus with high to moderate certainty. Arginine was beneficial for air stimulus, and strontium and potassium were beneficial for tactile stimulus, with moderate certainty.

Venous thromboembolism (VTE) is a relatively frequent complication in hospitalized patients, especially in those with risk factors. The benefit of using direct oral anticoagulants (DOACs) for prevention is controversial. This systematic review was performed as part of the American Society of Hematology (ASH) guidelines on VTE, developed in partnership with McMaster University. MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Epistemonikos were used as data sources from date of inception to November 2019. We included randomized trials in patients hospitalized for an acute medical disease, evaluating any DOACs vs other pharmacological prophylaxis, and included 3 trials with low risk of bias. We analyzed the effects of DOACs vs low-molecular-weight heparins (LMWHs) at 2 different time points: at the end of the short-term treatment phase (both drugs given for the same period of time) and at the end of the extended prophylaxis period (extended DOACs vs a shorter course of LMWHs). We observed that the use of DOACs did not reduce the risk of pulmonary embolism or symptomatic deep venous thrombosis (DVT) in comparison with LMWHs. However, the risk of major bleeding was slightly increased. Additionally, we observed that the benefit of DOACs previously reported was largely based on the reduction of asymptomatic DVT and was not apparent when only symptomatic events were considered. The use of DOACs in hospitalized medical patients slightly increases the risk of major bleeding with no appreciable benefit over LMWHs., (© 2020 by The American Society of Hematology.)

Values and preferences relate to the importance that patients place on health outcomes (eg, bleeding, having a deep venous thrombosis) and are essential when weighing benefits and harms in guideline recommendations. To inform the American Society of Hematology guidelines for management of venous thromboembolism (VTE) disease, we conducted a systematic review of patients' values and preferences related to VTE. We searched Medline, Embase, Cochrane Central Register of Controlled Trials, PsycINFO, and the Cumulative Index to Nursing and Allied Health Literature from inception to April of 2018 (PROSPERO-CRD42018094003). We included quantitative and qualitative studies. We followed Grading of Recommendations Assessment, Development and Evaluation (GRADE) guidance for rating the certainty and presenting findings for quantitative research about the relative importance of health outcomes and a grounded theory approach for qualitative thematic synthesis. We identified 14 quantitative studies (2465 participants) describing the relative importance of VTE-related health states in a widely diverse population of patients, showing overall small to important impact on patients' lives (certainty of the evidence from low to moderate). Additionally, evidence from 34 quantitative studies (6424 participants) and 15 qualitative studies (570 participants) revealed that patients put higher value on VTE risk reduction than on the potential harms of the treatment (certainty of evidence from low to moderate). Studies also suggested a clear preference for oral medication over subcutaneous medication (moderate certainty). The observed variability in health state values may be a result of differences in the approaches used to elicit them and the diversity of included populations rather than true variability in values. This finding highlights the necessity to explore the variability induced by different approaches to ascertain values., (© 2020 by The American Society of Hematology.)

Background: Venous thromboembolism (VTE) is a common source of perioperative morbidity and mortality., Objective: These evidence-based guidelines from the American Society of Hematology (ASH) intend to support decision making about preventing VTE in patients undergoing surgery., Methods: ASH formed a multidisciplinary guideline panel balanced to minimize bias from conflicts of interest. The McMaster University GRADE Centre supported the guideline-development process, including performing systematic reviews. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess evidence and make recommendations, which were subject to public comment., Results: The panel agreed on 30 recommendations, including for major surgery in general (n = 8), orthopedic surgery (n = 7), major general surgery (n = 3), major neurosurgical procedures (n = 2), urological surgery (n = 4), cardiac surgery and major vascular surgery (n = 2), major trauma (n = 2), and major gynecological surgery (n = 2)., Conclusions: For patients undergoing major surgery in general, the panel made conditional recommendations for mechanical prophylaxis over no prophylaxis, for pneumatic compression prophylaxis over graduated compression stockings, and against inferior vena cava filters. In patients undergoing total hip or total knee arthroplasty, conditional recommendations included using either aspirin or anticoagulants, as well as for a direct oral anticoagulant over low-molecular-weight heparin (LMWH). For major general surgery, the panel suggested pharmacological prophylaxis over no prophylaxis, using LMWH or unfractionated heparin. For major neurosurgery, transurethral resection of the prostate, or radical prostatectomy, the panel suggested against pharmacological prophylaxis. For major trauma surgery or major gynecological surgery, the panel suggested pharmacological prophylaxis over no prophylaxis.

Objectives: This study aimed to describe how colorectal practice guidelines (PGs) incorporate the patient perspective., Study Design and Setting: We searched in the Guidelines International Network library, MEDLINE, National Guideline Clearinghouse, NHS Evidence database, and TRIP database. Two authors independently selected the PGs. We considered recommendations rated or worded as weak or conditional or suggesting multiple options, as potentially preference sensitive. Two authors independently evaluated if, in potentially sensitive recommendations, the patient perspective was incorporated., Results: We included 28 PGs that contained 588 recommendations, being 256 potentially preference sensitive. Ten PGs (36%) included patients in the development process, and 12 (43%) provided information about patients' perspectives. Nine PGs (32%) included recommendations in which the patient perspective was explicitly considered, and 13 (46.4%) that recommended a discussion with the patient. From a total of 588 recommendations, 9.7% (25/256) of potentially preference-sensitive recommendations considered the patient perspective. The inclusion of patients in the development process was associated with a more frequent incorporation of the patient perspective in potentially preference sensitive recommendations (70% vs. 0%; P < 0.001)., Conclusions: Guideline users should be aware that the incorporation of the patient perspective in colorectal cancer PGs is suboptimal. Guideline developers should make efforts to incorporate the patient perspective, especially in preference-sensitive recommendations., (Copyright © 2019 Elsevier Inc. All rights reserved.)

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.)

Objectives: The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) working group defines patient values and preferences as the relative importance patients place on the main health outcomes. We provide GRADE guidance for assessing the risk of bias and indirectness domains for certainty of evidence about the relative importance of outcomes., Study Design and Setting: We applied the GRADE domains to rate the certainty of evidence in the importance of outcomes to several systematic reviews, iteratively reviewed draft guidance and consulted GRADE members and other stakeholders for feedback., Results: This is the first of two articles. A body of evidence addressing the importance of outcomes starts at "high certainty"; concerns with risk of bias, indirectness, inconsistency, imprecision, and publication bias lead to downgrading to moderate, low, or very low certainty. We propose subdomains of risk of bias as selection of the study population, missing data, the type of measurement instrument, and confounding; we have developed items for each subdomain. The population, intervention, comparison, and outcome elements associated with the evidence determine the degree of indirectness., Conclusion: This article provides guidance and examples for rating the risk of bias and indirectness for a body of evidence summarizing the importance of outcomes., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: To provide Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) guidance for assessing inconsistency, imprecision, and other domains for the certainty of evidence about the relative importance of outcomes., Study Design and Setting: We applied the GRADE domains to rate the certainty of evidence in the importance of outcomes to several systematic reviews, iteratively reviewed draft guidance, and consulted GRADE members and other stakeholders for feedback., Results: We describe the rationale for considering the remaining GRADE domains when rating the certainty in a body of evidence for the relative importance of outcomes. As meta-analyses are not common in this context, inconsistency and imprecision assessments are challenging. Furthermore, confusion exists about inconsistency, imprecision, and true variability in the relative importance of outcomes. To clarify this issue, we suggest that the true variability is neither equivalent to inconsistency nor imprecision. Specifically, inconsistency arises from population, intervention, comparison and outcome and methodological elements that should be explored and, if possible, explained. The width of the confidence interval and sample size inform judgments about imprecision. We also provide suggestions on how to detect publication bias and discuss the domains to rate up the certainty., Conclusion: We provide guidance and examples for rating inconsistency, imprecision, and other domains for a body of evidence describing the relative importance of outcomes., (Copyright © 2018. Published by Elsevier Inc.)

Allergen immunotherapy (AIT) has been in use for the treatment of allergic disease for more than 100 years. Asthma treatment relies mainly on corticosteroids and other controllers recommended to achieve and maintain asthma control, prevent exacerbations, and improve quality of life. AIT is underused in asthma, both in children and in adults. Notably, patients with allergic asthma not adequately controlled on pharmacotherapy (including biologics) represent an unmet health need. The European Academy of Allergy and Clinical Immunology has developed a clinical practice guideline providing evidence-based recommendations for the use of house dust mites (HDM) AIT as add-on treatment for HDM-driven allergic asthma. This guideline was developed by a multi-disciplinary working group using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. HDM AIT was separately evaluated by route of administration and children and adults: subcutaneous (SCIT) and sublingual AIT (SLIT), drops, and tablets. Recommendations were formulated for each. The important prerequisites for successful treatment with HDM AIT are (a) selection of patients most likely to respond to AIT and (b) use of allergen extracts and desensitization protocols of proven efficacy. To date, only AIT with HDM SLIT-tablet has demonstrated a robust effect in adults for critical end points (exacerbations, asthma control, and safety). Thus, it is recommended as an add-on to regular asthma therapy for adults with controlled or partially controlled HDM-driven allergic asthma (conditional recommendation, moderate-quality evidence). HDM SCIT is recommended for adults and children, and SLIT drops are recommended for children with controlled HDM-driven allergic asthma as the add-on to regular asthma therapy to decrease symptoms and medication needs (conditional recommendation, low-quality evidence)., (© 2019 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Background: Many interventions have shown effectiveness in reducing the duration of acute diarrhea and gastroenteritis (ADG) in children. Yet, there is lack of comparative efficacy of interventions that seem to be better than placebo among which, the clinicians must choose. Our aim was to determine the comparative effectiveness and safety of the pharmacological and nutritional interventions for reducing the duration of ADG in children., Methods: Data sources included Medline, Embase, CENTRAL, CINAHL, LILACS, and Global-Health up to May 2017. Eligible trials compared zinc (ZN), vitamin A, micronutrients (MN), probiotics, prebiotics, symbiotics, racecadotril, smectite(SM), loperamide, diluted milk, lactose-free formula(LCF), or their combinations, to placebo or standard treatment (STND), or among them. Two reviewers independently performed screening, review, study selection and extraction. The primary outcome was diarrhea duration. Secondary outcomes were stool frequency at day 2, diarrhea at day 3, vomiting and side effects. We performed a random effects Bayesian network meta-analysis to combine the direct and indirect evidence for each outcome. Mean differences and odds ratio with their credible intervals(CrI) were calculated. Coherence and transitivity assumptions were assessed. Meta-regression, subgroups and sensitivity analyses were conducted to explore the impact of effect modifiers. Summary under the cumulative curve (SUCRA) values with their CrI were calculated. We assessed the evidence quality and classified the best interventions using the Grading of Recommendations, Assessment, Development & Evaluation (GRADE) approach for each paired comparison., Results: A total of 174 studies (32,430 children) proved eligible. Studies were conducted in 42 countries of which most were low-and middle-income countries (LMIC). Interventions were grouped in 27 categories. Most interventions were better than STND. Reduction of diarrhea varied from 12.5 to 51.1 hours. The combinations Saccharomyces boulardii (SB)+ZN, and SM+ZN were considered the best interventions (i.e., GRADE quality of evidence: moderate to high, substantial superiority to STND, reduction in duration of 35 to 40 hours, and large SUCRA values), while symbiotics (combination of probiotics+prebiotics), ZN, loperamide and combinations ZN+MN and ZN+LCF were considered inferior to the best and better than STND [Quality: moderate to high, superior to STND, and reduction of 17 to 25 hours]. In subgroups analyses, effect of ZN was higher in LMIC and was not present in high-income countries (HIC). Vitamin A, MN, prebiotics, kaolin-pectin, and diluted milk were similar to STND [Quality: moderate to high]. The remainder of the interventions had low to very-low evidence quality. Loperamide was the only intervention with more side effects than STND [Quality: moderate]., Discussion/conclusion: Most interventions analyzed (except vitamin A, micronutrients, prebiotics, and kaolin-pectin) showed evidence of superiority to placebo in reducing the diarrhea. With moderate-to high-quality of evidence, SB+ZN and SM+ZN, demonstrated the best combination of evidence quality and magnitude of effect while symbiotics, loperamide and zinc proved being the best single interventions, and loperamide was the most unsafe. Nonetheless, the effect of zinc, SB+ZN and SM+ZN might only be applied to children in LMIC. Results suggest no further role for studies comparing interventions against no treatment or placebo, or studies testing loperamide, MN, kaolin-pectin, vitamin A, prebiotics and diluted milk., Prospero Registration: CRD42015023778., Competing Interests: The authors have declared that no competing interests exist.

Background: Venous thromboembolism (VTE) is the third most common vascular disease. Medical inpatients, long-term care residents, persons with minor injuries, and long-distance travelers are at increased risk., Objective: These evidence-based guidelines from the American Society of Hematology (ASH) intend to support patients, clinicians, and others in decisions about preventing VTE in these groups., Methods: ASH formed a multidisciplinary guideline panel balanced to minimize potential bias from conflicts of interest. 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 adult patients. The Grading of Recommendations Assessment, Development and Evaluation approach was used to assess evidence and make recommendations, which were subject to public comment., Results: The panel agreed on 19 recommendations for acutely ill and critically ill medical inpatients, people in long-term care facilities, outpatients with minor injuries, and long-distance travelers., Conclusions: Strong recommendations included provision of pharmacological VTE prophylaxis in acutely or critically ill inpatients at acceptable bleeding risk, use of mechanical prophylaxis when bleeding risk is unacceptable, against the use of direct oral anticoagulants during hospitalization, and against extending pharmacological prophylaxis after hospital discharge. Conditional recommendations included not to use VTE prophylaxis routinely in long-term care patients or outpatients with minor VTE risk factors. The panel conditionally recommended use of graduated compression stockings or low-molecular-weight heparin in long-distance travelers only if they are at high risk for VTE., (© 2018 by The American Society of Hematology.)

Background: To provide empirical evidence about prevalence, reporting and handling of missing outcome data in systematic reviews with network meta-analysis and acknowledgement of their impact on the conclusions., Methods: We conducted a systematic survey including all published systematic reviews of randomized controlled trials comparing at least three interventions from January 1, 2009 until March 31, 2017., Results: We retrieved 387 systematic reviews with network meta-analysis. Description of missing outcome data was available in 63 reviews. Intention-to-treat analysis was the most prevalent method (71%), followed by missing outcome data investigated as secondary outcome (e.g., acceptability) (40%). Bias due to missing outcome data was evaluated in half the reviews with explicit judgments in 18 (10%) reviews. Only 88 reviews interpreted their results acknowledging the implications of missing outcome data and mostly using the network meta-analysis results on missing outcome data as secondary outcome. We were unable to judge the actual strategy applied to deal with missing outcome data in 65% of the reviews due to insufficient information. Six percent of network meta-analyses were re-analyzed in sensitivity analysis considering missing outcome data, while 4% explicitly justified the strategy for dealing with missing outcome data., Conclusions: The description and handling of missing outcome data as well as the acknowledgment of their implications for the conclusions from network meta-analysis are deemed underreported.

Objective: To explore the impact of applying the Grading of Recommendations and Assessment, Development, and Evaluation (GRADE) approach to assess the certainty of the evidence in a published network meta-analysis (NMA) of antidepressant therapies., Study Design and Settings: We applied the GRADE approach to rate the certainty of the evidence for two outcomes, efficacy and acceptability, in each of the 66 paired comparisons within a previously published NMA assessing the relative efficacy and acceptability of 12 new-generation antidepressants., Results: For the outcome of efficacy, of the 25 comparisons in which the 95% CrI of OR excluded 1, 18 had certainty of evidence rated high or moderate. For the outcome of acceptability, of the 13 comparisons whose 95% CrI excluded 1, 10 had certainty of evidence rated high or moderate. Of the 11 comparisons involving sertraline, the antidepressants that the authors of the NMA suggested to be best, only 3 demonstrated it to be more effective and only 3 showed better tolerance, based on a 95% CrI excluding 1 and a high or moderate rating of certainty., Conclusions: In this example, application of GRADE highlighted varying evidence certainty, led to more conservative conclusions, and potentially avoided unwarranted strong inferences based on low certainty evidence., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: Summary of findings (SoF) tables present results of systematic reviews in a concise and explicit format. Adopted by many review groups including the Cochrane Collaboration and the Agency for Healthcare Research and Quality (AHRQ), optimal understanding of SoF table may be influenced by the type of information being conveyed and objectives or preferences of the end user. This study aims to compare three SoF table formats in terms of understanding, accessibility, satisfaction and preference with systematic review users., Methods: The primary objective of this three-arm randomised controlled non-inferiority trial is to investigate whether an alternative Grading of Recommendations Assessment, Development and Evaluation (GRADE) SoF table or Evidence-based Practice Center SoF table is non-inferior to the current GRADE SoF table in the understanding of the information presented to systematic review users, particularly for descriptive findings. Researchers, clinical practice guideline developers, policy-makers or knowledge transfer professionals will be recruited. Data will be collected electronically at baseline and after randomisation. Non-inferiority would be declared if the difference in the proportion of participants who understand the information displayed in the alternative SoF table is 10% or less., Ethics and Dissemination: The Hamilton Integrated Research Ethics Board reviewed this protocol. The findings from this study will be disseminated through a publication in a peer-reviewed journal., Trial Registration Number: NCT02813941., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: To date, a systematic review of the evidence regarding the association between vitamin D and allergic diseases development has not yet been undertaken., Objective: To review the efficacy and safety of vitamin D supplementation when compared to no supplementation in pregnant women, breastfeeding women, infants, and children for the prevention of allergies., Methods: Three databases were searched through January 30, 2016, including randomized (RCT) and nonrandomized studies (NRS). Two reviewers independently extracted data and assessed the certainty in the body of evidence using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach., Results: Among the 1932 articles identified, one RCT and four NRS were eligible. Very low certainty in the body of evidence across examined studies suggests that vitamin D supplementation for pregnant women, breastfeeding women, and infants may not decrease the risk of developing allergic diseases such as atopic dermatitis (in pregnant women), allergic rhinitis (in pregnant women and infants), asthma and/or wheezing (in pregnant women, breastfeeding women, and infants), or food allergies (in pregnant women). We found no studies of primary prevention of allergic diseases in children., Conclusion: Limited information is available addressing primary prevention of allergic diseases after vitamin D supplementation, and its potential impact remains uncertain., (© 2017 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.)

Background: Allergic rhinitis (AR) affects 10% to 40% of the population. It reduces quality of life and school and work performance and is a frequent reason for office visits in general practice. Medical costs are large, but avoidable costs associated with lost work productivity are even larger than those incurred by asthma. New evidence has accumulated since the last revision of the Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines in 2010, prompting its update., Objective: We sought to provide a targeted update of the ARIA guidelines., Methods: The ARIA guideline panel identified new clinical questions and selected questions requiring an update. We performed systematic reviews of health effects and the evidence about patients' values and preferences and resource requirements (up to June 2016). We followed the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) evidence-to-decision frameworks to develop recommendations., Results: The 2016 revision of the ARIA guidelines provides both updated and new recommendations about the pharmacologic treatment of AR. Specifically, it addresses the relative merits of using oral H 1 -antihistamines, intranasal H 1 -antihistamines, intranasal corticosteroids, and leukotriene receptor antagonists either alone or in combination. The ARIA guideline panel provides specific recommendations for the choice of treatment and the rationale for the choice and discusses specific considerations that clinicians and patients might want to review to choose the management most appropriate for an individual patient., Conclusions: Appropriate treatment of AR might improve patients' quality of life and school and work productivity. ARIA recommendations support patients, their caregivers, and health care providers in choosing the optimal treatment., (Copyright © 2017 American Academy of Allergy, Asthma & Immunology. All rights reserved.)

Objective: To conduct (1) a systematic survey of the reporting quality of simulation studies dealing with how to handle missing participant data (MPD) in randomized control trials and (2) summarize the findings of these studies., Study Design and Setting: We included simulation studies comparing statistical methods dealing with continuous MPD in randomized controlled trials addressing bias, precision, coverage, accuracy, power, type-I error, and overall ranking. For the reporting of simulation studies, we adapted previously developed criteria for reporting quality and applied them to eligible studies., Results: Of 16,446 identified citations, the 60 eligible generally had important limitations in reporting, particularly in reporting simulation procedures. Of the 60 studies, 47 addressed ignorable and 32 addressed nonignorable data. For ignorable missing data, mixed model was most frequently the best on overall ranking (9 times best, 34.6% of times tested) and bias (10, 55.6%). Multiple imputation was also performed well. For nonignorable data, mixed model was most frequently the best on overall ranking (7, 46.7%) and bias (8, 57.1%). Mixed model performance varied on other criteria. Last observation carried forward (LOCF) was very seldom the best performing, and for nonignorable MPD frequently the worst., Conclusion: Simulation studies addressing methods to deal with MPD suffered from serious limitations. The mixed model approach was superior to other methods in terms of overall performance and bias. LOCF performed worst., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: There are diverse opinions and confusion about defining and including patient values and preferences (i.e. the importance people place on the health outcomes) in the guideline development processes. This article aims to provide an overview of a process for systematically incorporating values and preferences in guideline development., Methods: In 2013 and 2014, we followed the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to adopt, adapt and develop 226 recommendations in 22 guidelines for the Ministry of Health of the Kingdom of Saudi Arabia. To collect context-specific values and preferences for each recommendation, we performed systematic reviews, asked clinical experts to provide feedback according to their clinical experience, and consulted patient representatives., Results: We found several types of studies addressing the importance of outcomes, including those reporting utilities, non-utility measures of health states based on structured questionnaires or scales, and qualitative studies. Guideline panels used the relative importance of outcomes based on values and preferences to weigh the balance of desirable and undesirable consequences of alternative intervention options. However, we found few studies addressing local values and preferences., Conclusions: Currently there are different but no firmly established processes for integrating patient values and preferences in healthcare decision-making of practice guideline development. With GRADE Evidence-to-Decision (EtD) frameworks, we provide an empirical strategy to find and incorporate values and preferences in guidelines by performing systematic reviews and eliciting information from guideline panel members and patient representatives. However, more research and practical guidance are needed on how to search for relevant studies and grey literature, assess the certainty of this evidence, and best summarize and present the findings.

Objectives: In systematic reviews of studies of patients' values and preferences, the objective of the study was to summarize items and domains authors have identified when considering the risk of bias (RoB) associated with primary studies., Study Design and Setting: We conducted a systematic survey of systematic reviews of patients' values and preference studies. Our search included three databases (MEDLINE, EMBASE, and PsycINFO) from their inception to August 2015. We conducted duplicate data extraction, focusing on items that authors used to address RoB in the primary studies included in their reviews and the associated underlying domains, and summarized criteria in descriptive tables., Results: We identified 42 eligible systematic reviews that addressed 23 items relevant to RoB and grouped the items into 7 domains: appropriate administration of instrument; instrument choice; instrument-described health state presentation; choice of participants group; description, analysis, and presentation of methods and results; patient understanding; and subgroup analysis., Conclusion: The items and domains identified provide insight into issues of RoB in patients' values and preference studies and establish the basis for an instrument to assess RoB in such studies., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Guideline developers can: (1) adopt existing recommendations from others; (2) adapt existing recommendations to their own context; or (3) create recommendations de novo. Monetary and nonmonetary resources, credibility, maximization of uptake, as well as logical arguments should guide the choice of the approach and processes., Objectives: To describe a potentially efficient model for guideline production based on adoption, adaptation, and/or de novo development of recommendations utilizing the Grading of Recommendations Assessment, Development and Evaluation (GRADE) Evidence to Decision (EtD) frameworks., Study Design and Setting: We applied the model in a new national guideline program producing 22 practice guidelines. We searched for relevant evidence that informs the direction and strength of a recommendation. We then produced GRADE EtDs for guideline panels to develop recommendations., Results: We produced a total of 80 EtD frameworks in approximately 4 months and 146 EtDs in approximately 6 months in two waves. Use of the EtD frameworks allowed panel members understand judgments of others about the criteria that bear on guideline recommendations and then make their own judgments about those criteria in a systematic approach., Conclusion: The "GRADE-ADOLOPMENT" approach to guideline production combines adoption, adaptation, and, as needed, de novo development of recommendations. If developers of guidelines follow EtD criteria more widely and make their work publically available, this approach should prove even more useful., (Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.)