Grading Of Recommendations Assessment, Development And Evaluation Framework Research Articles

Using causal diagrams within the Grading of Recommendations, Assessment, Development and Evaluation framework to evaluate confounding adjustment in observational studies

Background and ObjectivesThe current Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system instructs appraisers to evaluate whether individual observational studies have sufficiently adjusted for confounding. However, it does not provide an explicit, transparent, or reproducible method for doing so. This article explores how implementing causal graphs into the GRADE framework can help appraisers and end-users of GRADE products to evaluate the adequacy of confounding control from observational studies. MethodsUsing modern epidemiological theory, we propose a system for incorporating causal diagrams into the GRADE process to assess confounding control. ResultsIntegrating causal graphs into the GRADE framework enables appraisers to provide a theoretically grounded rationale for their evaluations of confounding control in observational studies. Additionally, the inclusion of causal graphs in GRADE may assist appraisers in demonstrating evidence for their appraisals in other domains of quality of evidence beyond confounding control. To support practical application, a worked example is included in the supplemental material to guide users through this approach. ConclusionGRADE calls for the explicit and transparent appraisal of evidence in the process of evidence synthesis. Incorporating causal diagrams into the evaluation of confounding control in observational studies aligns with the core principles of the GRADE framework, providing a clear, theory-based method for the adequacy of confounding control in observational studies.

Assessing the Effectiveness of eHealth Interventions to Manage Multiple Lifestyle Risk Behaviors Among Older Adults: Systematic Review and Meta-Analysis.

Developing adverse lifestyle behaviors increases the risk of a variety of chronic age-related diseases, including cardiovascular disease, obesity, and Alzheimer disease. There is limited evidence regarding the effectiveness of eHealth-based multiple health behavior change (MHBC) interventions to manage lifestyle risk behaviors. The purpose of this systematic evaluation was to assess the effectiveness of eHealth MHBC interventions in changing ≥2 major lifestyle risk behaviors in people aged ≥50 years. The literature search was conducted in 6 electronic databases-PubMed, Embase, Web of Science, Scopus, Cochrane Library, and SPORTDiscus-from inception to May 1, 2024. Eligible studies were randomized controlled trials of eHealth interventions targeting ≥2 of 6 behaviors of interest: alcohol use, smoking, diet, physical activity (PA), sedentary behavior, and sleep. A total of 34 articles with 35 studies were included. eHealth-based MHBC interventions significantly increased smoking cessation rates (odds ratio 2.09, 95% CI 1.62-2.70; P<.001), fruit intake (standardized mean difference [SMD] 0.18, 95% CI 0.04-0.32; P=.01), vegetable intake (SMD 0.17, 95% CI 0.05-0.28; P=.003), self-reported total PA (SMD 0.22, 95% CI 0.02-0.43; P=.03), and objectively measured moderate to vigorous PA (SMD 0.25, 95% CI 0.09-0.41; P=.002); in addition, the interventions decreased fat intake (SMD -0.23, 95% CI -0.33 to -0.13; P<.001). No effects were observed for alcohol use, sedentary behavior, or sleep. A sensitivity analysis was conducted to test the robustness of the pooled results. Moreover, the certainty of evidence was evaluated using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) framework. eHealth-based MHBC interventions may be a promising strategy to increase PA, improve diet, and reduce smoking among older adults. However, the effect sizes were small. Further high-quality, older adult-oriented research is needed to develop eHealth interventions that can change multiple behaviors. PROSPERO International Prospective Register of Systematic Reviews CRD42023444418; https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023444418.

The Pharmacological Management of Ketamine Use Disorder: A Systematic Review.

There has been limited evidence synthesis examining treatment of ketamine use disorder. We aimed to conduct a systematic review to assess the efficacy and tolerability of pharmacological interventions in the management of ketamine use disorder. We searched MEDLINE, EMBASE, PsychINFO, and CENTRAL (Cochrane Central Register of Controlled Trials) from database inception to November 14, 2023, for studies of any design that reported on any pharmacological intervention in the management of ketamine use disorder. We extracted any reported measure of efficacy or tolerability and assessed outcome quality using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) framework. We planned to combine outcomes using random-effects meta-analysis, where this was not possible results were reported narratively. Twelve studies met the inclusion criteria reporting on 368 participants. These comprised 1 controlled trial, 2 retrospective case series, and 9 case reports. Two studies reported on ketamine intoxication, 6 on withdrawal, and 4 on craving/relapse prevention. All studies reported only descriptive outcomes, and all evidence was of very low quality. Benzodiazepine regimens and haloperidol were reported to have potential utility in intoxication and withdrawal, whereas naltrexone, lamotrigine, and a combination of paliperidone palmitate and bupropion were reported to have potential utility in craving/relapse prevention. There is a paucity of research into pharmacological management of ketamine use disorder. The limited very low-quality evidence suggests benzodiazepine regimens may be most salient for future exploration in management of ketamine intoxication and withdrawal, whereas case reports suggest naltrexone, lamotrigine, and paliperidone palmitate plus bupropion may potentially merit further investigation with regard to craving/relapse prevention.

Computer-Aided Diagnosis for Leaving Colorectal Polyps In Situ : A Systematic Review and Meta-analysis.

Computer-aided diagnosis (CADx) allows prediction of polyp histology during colonoscopy, which may reduce unnecessary removal of nonneoplastic polyps. However, the potential benefits and harms of CADx are still unclear. To quantify the benefit and harm of using CADx in colonoscopy for the optical diagnosis of small (≤5-mm) rectosigmoid polyps. Medline, Embase, and Scopus were searched for articles published before 22 December 2023. Histologically verified diagnostic accuracy studies that evaluated the real-time performance of physicians in predicting neoplastic change of small rectosigmoid polyps without or with CADx assistance during colonoscopy. The clinical benefit and harm were estimated on the basis of accuracy values of the endoscopist before and after CADx assistance. The certainty of evidence was assessed using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) framework. The outcome measure for benefit was the proportion of polyps predicted to be nonneoplastic that would avoid removal with the use of CADx. The outcome measure for harm was the proportion of neoplastic polyps that would be not resected and left in situ due to an incorrect diagnosis with the use of CADx. Histology served as the reference standard for both outcomes. Ten studies, including 3620 patients with 4103 small rectosigmoid polyps, were analyzed. The studies that assessed the performance of CADx alone (9 studies; 3237 polyps) showed a sensitivity of 87.3% (95% CI, 79.2% to 92.5%) and specificity of 88.9% (CI, 81.7% to 93.5%) in predicting neoplastic change. In the studies that compared histology prediction performance before versus after CADx assistance (4 studies; 2503 polyps), there was no difference in the proportion of polyps predicted to be nonneoplastic that would avoid removal (55.4% vs. 58.4%; risk ratio [RR], 1.06 [CI, 0.96 to 1.17]; moderate-certainty evidence) or in the proportion of neoplastic polyps that would be erroneously left in situ (8.2% vs. 7.5%; RR, 0.95 [CI, 0.69 to 1.33]; moderate-certainty evidence). The application of optical diagnosis was only simulated, potentially altering the decision-making process of the operator. Computer-aided diagnosis provided no incremental benefit or harm in the management of small rectosigmoid polyps during colonoscopy. European Commission. (PROSPERO: CRD42023402197).

Acupuncture for vitiligo: An overview of systematic reviews and meta-analysis.

Vitiligo is a kind of refractory, autoimmune locally, or systemically generalized depigmentation spots caused by the disappearance of melanocyte function in the skin. Acupuncture and related therapies are extensively utilized for treating vitiligo in China. The objective of this study is to succinctly encapsulate and meticulously assess the methodological and reporting caliber of systematic reviews (SRs) pertaining to acupuncture and associated therapeutic approaches, while concurrently offering an all-encompassing body of evidence elucidating their efficacy and safety in the treatment of vitiligo. We performed an electronic literature search in eight databases to identify SRs that evaluated the efficacy of acupuncture therapy for vitiligo. The Assessment of Multiple Systematic Reviews 2 (AMSTAR 2) tool was used to evaluate the methodological and reporting quality of these SRs. The preferred reporting items for SRs and meta-analyses were followed according to PRISMA (2020) guidelines. Additionally, the risk of bias in systematic reviews (ROBIS) was assessed to evaluate potential bias. The quality of evidence for outcome measures was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework. This study included 10 SRs and assessed a total of 13 outcome measures, all of which were published before June 2023. Acupuncture therapy was more effective than control conditions for the treatment of Vitiligo. The AMSTAR-2 results indicated a critical deficiency in the methodological quality of all SRs, with items 7 and 16 demonstrating notably low quality. The reporting quality of the included SRs according to PRISMA was deemed unsatisfactory, with significant reporting flaws identified in the areas of Protocol and registration, Risk of bias across studies, Study selection, and Limitations. According to the ROBIS assessment, 5 out of the total number of SRs (50.00%) were found to have a high risk of bias. Out of the total of 62 outcomes evaluated using the GRADE framework, 9 outcomes (14.51%) exhibited high-quality evidence, 20 outcomes (32.26%) demonstrated moderate-quality evidence, 19 outcomes (30.65%) presented low-quality evidence, while 14 outcomes (22.58%) indicated very low-quality evidence. This overview shows that Acupuncture therapy was more effective than the control treatment for Vitiligo. Nevertheless, given the subpar methodological quality of the reviews, we recommend conducting studies with stricter designs, larger sample sizes, and improved methodological and reporting quality to yield more robust evidence.

Comparing Oral Versus Intravenous Antibiotics Administration for Cellulitis Infection: Protocol for a Systematic Review and Meta-Analysis

Background Cellulitis is defined as an infection of the skin that is usually characterized by localized but poorly demarcated areas of erythema, swelling, and pain. Erysipelas is a subtype of cellulitis that is characterized by a more superficial infection, often involving the face. Because gram-positive bacteria are the most common infective agent, beta-lactam antibiotics such as cephalosporins are commonly used. However, guidelines and physician preference vary widely as different antibiotic options and routes of administration exist, in addition to the fact that most cases are treated empirically without microbiological lab guidance. This lack of standardization in evidence, guidelines, and physician practice prompted this systematic review and meta-analysis of both randomized trial data and cohort studies to aggregate the currently available evidence for the optimal routes of antibiotic administration in cellulitis treatment. Objective The primary objective of our review is to compare the efficacy of oral versus intravenous antibiotic administration for cellulitis infections, thereby providing clinicians with evidence-based guidelines for treatment. Methods We will search MEDLINE, Embase, and CENTRAL through Ovid as well as Web of Science and CINAHL for all available literature comparing different routes of antibiotic administration in the treatment of cellulitis and erysipelas. We will perform title and abstract as well as full-text screening in duplicate according to the PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analyses) guidelines and then extract the relevant data using a prepiloted data sheet. The primary outcome for our review is the duration of infection resolution, and secondary outcomes such as incidence of sepsis, mortality, hospital admission, and Clostridium difficile infection. We will assess the risk of bias in our included studies using the RoB 2.0 (revised tool for Risk of Bias in randomized trials) and ROBINS-I (Risk of bias in non-randomized studies for interventions) tools, with a final quality assessment using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) framework and a sensitivity analysis to examine heterogeneity. Results We will publish the final results of our systematic review in a peer-reviewed academic journal. This project received no funding or financial assistance. Data analysis is currently underway, and the results are expected to be submitted for publication in late November 2023. Conclusions To our knowledge, this will be the most up-to-date review of the best available evidence comparing different routes of antibiotic administration for cellulitis. Because of the vast selection of antibiotic options available and the empirical nature of the treatment, we anticipate heterogeneity within our data but nonetheless hope to provide aggregated evidence on the efficacy of intravenous versus oral administration of antibiotics in cellulitis treatment. We hope the results from this study will better inform physician practices in the future for cellulitis infections. International Registered Report Identifier (IRRID) PRR1-10.2196/48342

Clinical practice guideline for management of osteoporosis and fracture prevention in Canada: 2023 update.

In Canada, more than 2 million people live with osteoporosis, a disease that increases the risk for fractures, which result in excess mortality and morbidity, decreased quality of life and loss of autonomy. This guideline update is intended to assist Canadian health care professionals in the delivery of care to optimize skeletal health and prevent fractures in postmenopausal females and in males aged 50 years and older. This guideline is an update of the 2010 Osteoporosis Canada clinical practice guideline on the diagnosis and management of osteoporosis in Canada. We followed the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework and quality assurance as per Appraisal of Guidelines for Research and Evaluation (AGREE II) quality and reporting standards. Primary care physicians and patient partners were represented at all levels of the guideline committees and groups, and participated throughout the entire process to ensure relevance to target users. The process for managing competing interests was developed before and continued throughout the guideline development, informed by the Guideline International Network principles. We considered benefits and harms, patient values and preferences, resources, equity, acceptability and feasibility when developing recommendations; the strength of each recommendation was assigned according to the GRADE framework. The 25 recommendations and 10 good practice statements are grouped under the sections of exercise, nutrition, fracture risk assessment and treatment initiation, pharmacologic interventions, duration and sequence of therapy, and monitoring. The management of osteoporosis should be guided by the patient's risk of fracture, based on clinical assessment and using a validated fracture risk assessment tool. Exercise, nutrition and pharmacotherapy are key elements of the management strategy for fracture prevention and should be individualized. The aim of this guideline is to empower health care professionals and patients to have meaningful discussions on the importance of skeletal health and fracture risk throughout older adulthood. Identification and appropriate management of skeletal fragility can reduce fractures, and preserve mobility, autonomy and quality of life.

Real-Time Computer-Aided Detection of Colorectal Neoplasia During Colonoscopy : A Systematic Review and Meta-analysis.

Artificial intelligence computer-aided detection (CADe) of colorectal neoplasia during colonoscopy may increase adenoma detection rates (ADRs) and reduce adenoma miss rates, but it may increase overdiagnosis and overtreatment of nonneoplastic polyps. To quantify the benefits and harms of CADe in randomized trials. Systematic review and meta-analysis. (PROSPERO: CRD42022293181). Medline, Embase, and Scopus databases through February 2023. Randomized trials comparing CADe-assisted with standard colonoscopy for polyp and cancer detection. Adenoma detection rate (proportion of patients with ≥1 adenoma), number of adenomas detected per colonoscopy, advanced adenoma (≥10 mm with high-grade dysplasia and villous histology), number of serrated lesions per colonoscopy, and adenoma miss rate were extracted as benefit outcomes. Number of polypectomies for nonneoplastic lesions and withdrawal time were extracted as harm outcomes. For each outcome, studies were pooled using a random-effects model. Certainty of evidence was assessed using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) framework. Twenty-one randomized trials on 18 232 patients were included. The ADR was higher in the CADe group than in the standard colonoscopy group (44.0% vs. 35.9%; relative risk, 1.24 [95% CI, 1.16 to 1.33]; low-certainty evidence), corresponding to a 55% (risk ratio, 0.45 [CI, 0.35 to 0.58]) relative reduction in miss rate (moderate-certainty evidence). More nonneoplastic polyps were removed in the CADe than the standard group (0.52 vs. 0.34 per colonoscopy; mean difference [MD], 0.18 polypectomy [CI, 0.11 to 0.26 polypectomy]; low-certainty evidence). Mean inspection time increased only marginally with CADe (MD, 0.47 minute [CI, 0.23 to 0.72 minute]; moderate-certainty evidence). This review focused on surrogates of patient-important outcomes. Most patients, however, may consider cancer incidence and cancer-related mortality important outcomes. The effect of CADe on such patient-important outcomes remains unclear. The use of CADe for polyp detection during colonoscopy results in increased detection of adenomas but not advanced adenomas and in higher rates of unnecessary removal of nonneoplastic polyps. European Commission Horizon 2020 Marie Skłodowska-Curie Individual Fellowship.

Minor tranquillizers for short-term treatment of newly onset symptoms of anxiety and distress: a systematic review with network meta-analysis of randomized trials

Unspecific symptoms of anxiety and distress are frequently encountered in patients in both general practice and acute psychiatric services. Minor tranquillizers may be a treatment option when non-pharmacological interventions are insufficient or unavailable. We conducted a systematic review with network meta-analysis of the evidence for short-term (1–4 weeks) pharmacological treatment of newly onset symptoms of anxiety and distress. We searched the PsycInfo, MEDLINE, EMBASE and Cochrane Library databases and extracted data following a predefined hierarchy of outcomes. We assessed risk of bias using the Cochrane Risk of Bias tool and the certainty of the evidence using the Grading of Recommendations Assessment, Development and Evaluation framework (GRADE). We included 34 randomized trials comprising a total of 7044 patients with adjustment disorders or anxiety spectrum disorders. The network meta-analysis showed that regarding the critical outcome symptoms of anxiety within 1–4 weeks benzodiazepines (SMD − 0.58, 95% CI − 0.77 to − 0.40), quetiapine (SMD − 0.51, 95% CI − 0.90 to − 0.13) and pregabalin (SMD − 0.58, 95% CI − 0.87 to − 0.28) all performed better than placebo with no statistically significant difference between the drugs. Data on other important outcomes were inconsistently reported. Adverse effects varied, but overall, it was uncertain whether adverse effects differed between interventions. The evidence regarding the risk of dependence was uncertain, but dependence may be a concern in susceptible individuals even with short-term treatment. Overall, the certainty of the evidence according to GRADE was rated as low to very low across outcomes. Despite the limitations in the evidence, the results of this review can inform treatment guidelines, supporting clinicians in the choice of minor tranquillizer in this prevalent and help-seeking, clinically heterogeneous population.

GRADE concept 4: rating the certainty of evidence when study interventions or comparators differ from PICO targets

ObjectivesThis Grading of Recommendations Assessment, Development and Evaluation (GRADE) concept article offers systematic reviewers, guideline authors, and other users of evidence assistance in addressing randomized trial situations in which interventions or comparators differ from those in the target people, interventions, comparators, and outcomes. To clarify what GRADE considers under indirectness of interventions and comparators, we focus on a particular example: when comparator arm participants receive some or all aspects of the intervention management strategy (treatment switching). Study Design and SettingAn interdisciplinary panel of the GRADE working group members developed this concept article through an iterative review of examples in multiple teleconferences, small group sessions, and e-mail correspondence. After presentation at a GRADE working group meeting in November 2022, attendees approved the final concept paper, which we support with examples from systematic reviews and individual trials. ResultsIn the presence of safeguards against risk of bias, trials provide unbiased estimates of the effect of an intervention on the people as enrolled, the interventions as implemented, the comparators as implemented, and the outcomes as measured. Within the GRADE framework, differences in the people, interventions, comparators, and outcomes elements between the review or guideline recommendation targets and the trials as implemented constitute issues of indirectness. The intervention or comparator group management strategy as implemented, when it differs from the target comparator, constitutes one potential source of indirectness: Indirectness of interventions and comparators—comparator group receipt of the intervention constitutes a specific subcategory of said indirectness. The proportion of comparator arm participants that received the intervention and the apparent magnitude of effect bear on whether one should rate down, and if one does, to what extent. ConclusionTreatment switching and other differences between review or guideline recommendation target interventions and comparators vs. interventions and comparators as implemented in otherwise relevant trials are best considered issues of indirectness.

Effects of gluten on dyspeptic symptoms: a systematic review and meta-analysis of clinical trials.

Research on the effects of gluten on dyspeptic symptoms has shown conflicting results. The aim of this systematic review and meta-analysis of clinical trials was to assess the effects of gluten on dyspeptic symptoms. A systematic search of the PubMed, ISI Web of Science, Scopus, Cochrane, and Embase online databases was performed up to May 2022. Randomized controlled trials (RCTs) and non-RCTs that examined the impact of a gluten-free diet, a low-gluten diet, or a gluten challenge on dyspeptic symptoms, including early satiety, epigastric pain, bloating, and nausea, were selected independently by 2 authors. The GRADE (Grading of Recommendations Assessment, Development, and Evaluation) framework was used to assess the certainty of the evidence. Results were pooled using a random-effects model and expressed as weighted mean differences (WMDs) and 95%CIs. Of the 7641 citations retrieved, 27 articles (18 RCTs and 9 non-RCTs) were included in the systematic review. Of those, 5 RCTs were eligible for the meta-analysis. The pooled results indicated that gluten challenge significantly increased the severity of bloating (WMD = 0.67; 95%CI, 0.37-0.97; I2 = 81.8%; n = 6), early satiety (WMD = 0.91; 95%CI, 0.58-1.23; I2 = 27.2%; n = 5), and epigastric pain (WMD = 0.46; 95%CI, 0.17-0.75; I2 = 65.8%; n = 6). However, the effect of gluten challenge on the severity of nausea (WMD = 0.13; 95%CI, -0.17 to 0.43; I2 = 0.0%, n = 5) was nonsignificant. Gluten challenge significantly worsened dyspeptic symptoms, including bloating, early satiety, and epigastric pain, but did not affect nausea. These findings suggest that gluten restriction could be efficient in reducing dyspeptic symptoms. Well-designed large RCTs recruiting homogenous groups of patients with functional dyspepsia are needed to clarify the effectiveness of gluten restriction on dyspeptic symptoms.

Acupuncture and Related Therapies for Chronic Urticaria: A Critical Overview of Systematic Reviews.

Chronic urticaria (CU) can severely impair the quality of life. Acupuncture and related therapies have been widely used in the treatment of CU in China. This study aimed to summarize and critically evaluate the methodological and reporting quality of relevant systematic reviews (SRs) and present objective and comprehensive evidence on the effectiveness and safety of acupuncture and related therapies for CU. Eight electronic databases were searched from inception to October 2021 for SRs examining acupuncture and related therapies for CU, and gray literature was manually searched. Two authors independently identified SRs and extracted data. The methodological and reporting quality of these SRs were assessed by the Assessment of Multiple Systematic Reviews 2 (AMSTAR 2) tool and preferred reporting items for SRs and meta-analyses (PRISMA, 2020), respectively. In addition, the risk of bias in systematic reviews (ROBIS) was used to evaluate the risk of bias. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework was applied to evaluate the quality of evidence for outcome measures. In total, 23 SRs, including a total of 11 outcome indicators, were published before October 2021. The AMSTAR-2 results showed that the methodological quality of all SRs was critically low; items 2, 3, 7, 9, 10, and 16 were found to have particularly low quality. For PRISMA, the reporting quality of the included SRs was unsatisfactory, and major reporting flaws were observed in the search strategy, synthesis method, certainly assessment, reporting biases, registrations, and financial support of the included SRs. For ROBIS, 22 SRs (95.65%) had a high risk of bias. Among the 55 outcomes assessed using the GRADE framework, there were 3 (5.45%) outcomes with moderate-quality evidence, 6 (10.91%) outcomes with low-quality evidence, and 46 (83.64%) outcomes with very low-quality evidence. We found the moderate quality of evidence indicating that the total effective rate and curing rate of the acupuncture group were higher than those of the western medicine group, and the recurrence rate was lower than that of the western medicine group. Acupuncture and related therapies for the treatment of CU are supported by low-quality evidence-based medicine. However, considering the poor quality of these SRs, we suggest that studies with more rigorous designs, larger sample sizes, and higher methodological and reporting quality are necessary to provide stronger evidence. Registration. The protocol for this study has been registered (PROSPERO registration number: CRD42021259131).

Clinical recommendations: The role of mechanisms in the GRADE framework

The Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework has become one of the most influential frameworks for assessing quality of research and developing clinical recommendations. The GRADE framework has been presented as an evolution in the Evidence-Based Medicine (EBM) movement. Both GRADE and EBM emphasize effect estimates derived from population-level clinical trials and, as a consequence, devalue the role of mechanisms as the basis for clinical decisions. Although mechanisms do not hold the epistemic privilege of rigorous clinical trials in EBM reasoning, this paper will argue that mechanisms appear to be important in the use and application of GRADE, as described in the literature. The seemingly necessary role of mechanisms in the development of clinical recommendations has, so far, received little attention and is not explicitly featured in the literature describing GRADE. The analysis of the GRADE framework presented in this paper reveals an apparent tension between EBM's willingness to downplay mechanisms and what seems their inevitable use in GRADE. In this paper, we take the position that if mechanistic reasoning is inevitable in the use of GRADE, then the instructional literature on the framework would benefit from more explicit discussion of how to consider and integrate mechanisms.

Clinical Practice Guidelines From the Association for the Advancement of Blood and Biotherapies (AABB): COVID-19 Convalescent Plasma.

Coronavirus disease 2019 convalescent plasma (CCP) has emerged as a potential treatment of COVID-19. However, meta-analysis data and recommendations are limited. The Association for the Advancement of Blood and Biotherapies (AABB) developed clinical practice guidelines for the appropriate use of CCP. These guidelines are based on 2 living systematic reviews of randomized controlled trials (RCTs) evaluating CCP from 1 January 2019 to 26 January 2022. There were 33 RCTs assessing 21916 participants. The results were summarized using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) method. An expert panel reviewed the data using the GRADE framework to formulate recommendations. The AABB suggests CCP transfusion in addition to the usual standard of care for outpatients with COVID-19 who are at high risk for disease progression (weak recommendation, moderate-certainty evidence). The AABB recommends against CCP transfusion for unselected hospitalized persons with moderate or severe disease (strong recommendation, high-certainty evidence). This recommendation does not apply to immunosuppressed patients or those who lack antibodies against SARS-CoV-2. The AABB suggests CCP transfusion in addition to the usual standard of care for hospitalized patients with COVID-19 who do not have SARS-CoV-2 antibodies detected at admission (weak recommendation, low-certainty evidence). The AABB suggests CCP transfusion in addition to the usual standard of care for hospitalized patients with COVID-19 and preexisting immunosuppression (weak recommendation, low-certainty evidence). The AABB suggests against prophylactic CCP transfusion for uninfected persons with close contact exposure to a person with COVID-19 (weak recommendation, low-certainty evidence). CCP is most effective when transfused with high neutralizing titers to infected patients early after symptom onset.

Antifungal prophylaxis in adult lung transplant recipients: Uncertainty despite 30 years of experience. A systematic review of the literature and network meta‐analysis

Invasive fungal infections (IFI), particularly invasive aspergillosis (IA), cause significant morbidity and mortality in lung transplant (LTx) recipients. The optimum strategy and antifungal agents for prevention are unclear. We performed a comprehensive literature search, systematic review, and network meta-analysis using a frequentist framework to compare the efficacy of various antifungal drugs on the incidence of IA/IFI in the setting of universal prophylaxis or no prophylaxis following lung transplantation. We included 13 eligible studies comprising of 1515 LTx recipients and 12 different prophylaxis strategies/antifungal combinations. The greatest number of direct comparisons were between the inhaled amphotericin formulations. The top three ranked treatments were inhaled liposomal amphotericin B (L-AmB), inhaled amphotericin deoxycholate (AmBd), and itraconazole plus inhaled amphotericin B (AmB). Among the azoles, isavuconazole ranked highest. The certainty of the evidence, assessed using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) framework, was very low. Although universal antifungal prophylaxis post lung transplantation is commonly used, robust data from randomized controlled trials (RCTs) to inform the choice of antifungal agent and prophylaxis strategy are lacking. This exploratory network meta-analysis provides insight into the probable relative effectiveness of various antifungal agents in preventing IA, and this analysis should serve as a guide when selecting antifungals to be assessed in a RCT.

Role of routine second-look endoscopy in patients with acute peptic ulcer bleeding: meta-analysis of randomized controlled trials

Studies evaluating the role of routine second-look endoscopy in patients with acute upper GI bleed because of peptic ulcer disease (PUD) have reported conflicting results. This meta-analysis evaluates the usefulness of routine second-look endoscopy in these patients. We reviewed several databases from inception to September 15, 2020 to identify randomized controlled trials (RCTs) that compared routine second-look endoscopy with no planned second-look endoscopy in patients with acute upper GI bleed because of PUD. Our outcomes of interest were recurrent bleeding, mortality, need for surgery, and mean number of units of blood transfused. For categorical variables, we calculated pooled risk ratios (RRs) with 95% confidence intervals (CIs); for continuous variables, we calculated standardized mean difference with 95% CIs. Data were analyzed using a random effects model. We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework to ascertain the quality of evidence. We included 9 RTCs comprising 1452 patients; 726 patients underwent planned/routine second-look endoscopy and 726 did not. We found no significant difference in recurrent bleeding (RR, .79; 95% CI, .51-1.23), need for surgery (RR, .58; 95% CI, .29-1.15), mortality (RR, .69; 95% CI, .33-1.45), or mean number of units of blood transfused (standardized mean difference, -.06; 95% CI, -.19 to .07). Quality of evidence ranged from low to moderate based on the GRADE framework. Single endoscopy with complete endoscopic hemostasis is not inferior to routine second-look endoscopy in reducing the risk of recurrent bleeding, mortality, or need for surgery in patients with acute upper GI bleed because of PUD.

Management of prepregnancy, pregnancy, and postpartum obesity from the FIGO Pregnancy and Non‐Communicable Diseases Committee: A FIGO (International Federation of Gynecology and Obstetrics) guideline

Management of prepregnancy, pregnancy, and postpartum obesity from the FIGO Pregnancy and Non‐Communicable Diseases Committee: A FIGO (International Federation of Gynecology and Obstetrics) guideline

AGA Institute Rapid Review and Recommendations on the Role of Pre-Procedure SARS-CoV-2 Testing and Endoscopy

AGA Institute Rapid Review and Recommendations on the Role of Pre-Procedure SARS-CoV-2 Testing and Endoscopy

AGA Rapid Recommendations for Gastrointestinal Procedures During the COVID-19 Pandemic

Abbreviations used in this paper AGAAmerican Gastroenterological AssociationCDCCenters for Disease Control and PreventionCIconfidence intervalCOVID-19coronavirus disease 2019GIgastrointestinalGRADEGrading of Recommendations Assessment, Development and EvaluationMERS-CoVMiddle East respiratory syndrome–related coronavirusORodds ratioPAPRpowered air-purifying respiratorPPEpersonal protective equipmentRRrisk ratioSARS-CoV-2severe acute respiratory syndrome coronavirus 2WHOWorld Health Organization

1155 Temporal Trends of Discordant Recommendations in Gastroenterology Guidelines Over the Last 5 Years

INTRODUCTION: Within the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) framework, recommendations are accompanied by a strength of recommendation (strong/conditional) along with an assessment of the certainty of evidence (high/moderate/low/very low). Strong recommendations based on lower certainty evidence are termed “discordant recommendations.” While generally not considered appropriate, within GRADE there are 5 situations in which such recommendations may be warranted: Strong recommendations FOR an intervention can be made when there is 1) only low/very low certainty of benefit but you have a life-threatening problem, 2) low/very low certainty of equivalence in benefit of two interventions but one is associated with less harm. Strong recommendations AGAINST the intervention can be made when there is 1) low/very low certainty of harm but the harm is catastrophic and 2) high certainty of similar benefits of two alternatives but one is less harmful, and 3)low/very low certainty of benefit but one is more harmful. We strived to assess the prevalence of GRADE recommendations and temporal trends of discordant recommendations (DR). METHODS: Guidelines produced by AASLD, ACG, AGA, and ASGE from 2013 to October 15, 2018 that used GRADE, were reviewed. Across all guidelines, we identified the prevalence of and temporal trends of DRs. RESULTS: A total of 87 guidelines were identified and of these 78 (89.6%) were based on the GRADE framework. Across these 78 guidelines a total of 1,443 recommendation statements were generated. The number of DRs that did not fit the 5 paradigmatic scenarios above by year were as follows: 2013 = 12.7 % (45/353), 2014 = 15.9 % (50/313), 2015 = 19.5 % (60/307), 2016 = 29.3% (54/184), 2017 = 17.9% (32/178), 2018 = 17.5% (19/108) [Figure 1]. CONCLUSION: Discordant recommendations are discouraged because when either the benefits or harms of an intervention are uncertain, one cannot be confident that an intervention does more good than harm. Over the last 5 years, the number of DRs in gastroenterology guidelines increased until 2016 and then started to downtrend. Further investigations should explore the etiology of why discordant recommendations are made as they may contribute to patients receiving suboptimal care.