Grading Of Recommendations Assessment, Development And Evaluation Approach Research Articles

Newer Pharmacologic Treatments in Adults With Type 2 Diabetes: A Clinical Guideline From the American College of Physicians.

The American College of Physicians (ACP) developed this clinical guideline to update recommendations on newer pharmacologic treatments of type 2 diabetes. This clinical guideline is based on the best available evidence for effectiveness, comparative benefits and harms, consideration of patients' values and preferences, and costs. This clinical guideline is based on a systematic review of the effectiveness and harms of newer pharmacologic treatments of type 2 diabetes, including glucagon-like peptide-1 (GLP-1) agonists, a GLP-1 agonist and glucose-dependent insulinotropic polypeptide agonist, sodium-glucose cotransporter-2 (SGLT-2) inhibitors, dipeptidyl peptidase-4 (DPP-4) inhibitors, and long-acting insulins, used either as monotherapy or in combination with other medications. The Clinical Guidelines Committee prioritized the following outcomes, which were evaluated using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach: all-cause mortality, major adverse cardiovascular events, myocardial infarction, stroke, hospitalization for congestive heart failure, progression of chronic kidney disease, serious adverse events, and severe hypoglycemia. Weight loss, as measured by percentage of participants who achieved at least 10% total body weight loss, was a prioritized outcome, but data were insufficient for network meta-analysis and were not rated with GRADE. The audience for this clinical guideline is physicians and other clinicians. The population is nonpregnant adults with type 2 diabetes. ACP recommends adding a sodium-glucose cotransporter-2 (SGLT-2) inhibitor or glucagon-like peptide-1 (GLP-1) agonist to metformin and lifestyle modifications in adults with type 2 diabetes and inadequate glycemic control (strong recommendation; high-certainty evidence). ACP recommends against adding a dipeptidyl peptidase-4 (DPP-4) inhibitor to metformin and lifestyle modifications in adults with type 2 diabetes and inadequate glycemic control to reduce morbidity and all-cause mortality (strong recommendation; high-certainty evidence).

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

BackgroundCow's milk allergy (CMA) is the most common food allergy in infants. The replacement with specialized formulas is an established clinical approach to ensure adequate growth and minimize the risk of severe allergic reactions when breastfeeding is not possible. Still, given the availability of multiple options, such as extensively hydrolyzed cow's milk protein formula (eHF-CM), amino acid formula (AAF), hydrolyzed rice formula (HRF) and soy formulas (SF), there is some uncertainty as to the most suitable choice with respect to health outcomes. Furthermore, the addition of probiotics to a formula has been proposed as a potential approach to maximize benefit. ObjectiveThese evidence-based guidelines from the World Allergy Organization (WAO) intend to support patients, clinicians, and others in decisions about the use of milk specialized formulas, with and without probiotics, for individuals with CMA. MethodsWAO formed a multidisciplinary guideline panel balanced to include the views of all stakeholders and to minimize potential biases from competing interests. The McMaster University GRADE Centre supported the guideline-development process, including updating or performing systematic evidence reviews. The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used, including GRADE Evidence-to-Decision frameworks, which were subject to review by stakeholders. ResultsAfter reviewing the summarized evidence and thoroughly discussing the different management options, the WAO guideline panel suggests: a) using an extensively hydrolyzed (cow's milk) formula or a hydrolyzed rice formula as the first option for managing infants with immunoglobulin E (IgE) and non-IgE-mediated CMA who are not being breastfed. An amino-acid formula or a soy formula could be regarded as second and third options respectively; b) using either a formula without a probiotic or a casein-based extensively hydrolyzed formula containing Lacticaseibacillus rhamnosus GG (LGG) for infants with either IgE or non-IgE-mediated CMA.The issued recommendations are labeled as “conditional” following the GRADE approach due to the very low certainty about the health effects based on the available evidence. ConclusionsIf breastfeeding is not available, clinicians, patients, and their family members might want to discuss all the potential desirable and undesirable consequences of each formula in infants with CMA, integrating them with the patients' and caregivers’ values and preferences, local availability, and cost, before deciding on a treatment option. We also suggest what research is needed to determine with greater certainty which formulas are likely to be the most beneficial, cost-effective, and equitable.

Risk factors for infant hearing loss: a meta-analysis.

Hearing loss is a common disability in infants that significantly impacts their cognitive, language, and literacy development. This study aimed to systematically assess the risk factors for the early identification and intervention in infant hearing loss. Databases were searched for meta-analyses of observational studies until November 2023. The quality assessment was performed using the Cochrane risk of bias tool, and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to assess the certainty of the evidence. A meta-analysis identified 14 risk factors significantly associated with infant hearing loss. According to the GRADE approach, there were four factors with moderate-certainty evidence (low birth weight(LBW), congenital anomalies, craniofacial anomalies, intracranial hemorrhages), seven factors with low-certainty evidence (ototoxic medications, family history of hearing loss, mechanical ventilation > 5 days, intrauterine infection, admission to neonatal intensive care unit (NICU) > 5 days, mechanical ventilation and asphyxia) and six with extremely-low-certainty evidence (very low birth weight < 1500 g (VLBW), hyperbilirubinemia, sepsis or meningitis, male sex, premature birth, small for gestational age (SGA)). Nevertheless, no significant association was found between infant hearing loss and factors such as small for gestational age (SGA), male sex, and premature birth (P > 0.05). Conclusion: The identification of these 14 interrelated risk factors can prove advantageous in clinical practice, as these findings could guide hearing screening and parental counseling. Furthermore, prospective research could be conducted to develop risk-based scoring systems based on these factors. What is Known: • Infant hearing loss is a worldwide issue. • Risk factors for this condition are debated. What is New: • This is the first meta-analysis to comprehensively evaluate perinatal and postnatal risk factors for hearing loss in infants. • Intracranial hemorrhage, mechanical ventilation, and low birth weight are associated with infant hearing loss. However, no evidence of an association was found between premature birth, being small for gestational age, or male sex and hearing loss.

Patient-Centered Practice Guidelines: GRADEing Evidence to Incorporate Certainty, Balance Between Benefits and Harms, Equity, Feasibility, and Cost-Effectiveness

The practice of medicine in recent years has emphasized the use of evidence-based clinical guidelines to help inform treatment decisions. Since its development in 2004, the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach has offered a systematic process for reviewing and summarizing the certainty of evidence found in the medical literature regarding various treatment options. To develop truly patient-centered care guidelines, this appraisal of the certainty of evidence must be combined with an understanding of the balance between benefits and harms, patient preferences, equity, feasibility, cost-effectiveness, and policy implications. This review examines each of these domains in detail, exploring the process and benefits of developing relevant, patient-focused guidelines directly applicable to the practice of modern medicine.

Virtual Reality-Based Training in Chronic Low Back Pain: Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Low back pain is one of the most prevalent pain conditions worldwide. Virtual reality-based training has been used for low back pain as a new treatment strategy. Present evidence indicated that the effectiveness of virtual reality-based training for people with chronic low back pain is inconclusive. This study conducted a meta-analysis to evaluate the immediate- and short-term effects of virtual reality-based training on pain, pain-related fear, and disability in people with chronic low back pain. We searched the PubMed, Embase, Web of Science, PEDro, CENTRAL, and CINAHL databases from inception until January 2024. Only randomized controlled trials assessing the effects of virtual reality-based training on individuals with chronic low back pain were selected. The outcomes were focused on pain, pain-related fear measured by the Tampa Scale of Kinesiophobia, and disability measured by the Oswestry Disability Index. The immediate term was defined as the immediate period after intervention, and the short term was defined as 3 to 6 months after intervention. The Cochrane Risk of Bias tool and the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach were used to evaluate the quality of the methodology and evidence, respectively. In total, 20 randomized controlled trials involving 1059 patients were eligible for analysis. Virtual reality-based training showed significant improvements in pain (mean difference [MD] -1.43; 95% CI -1.86 to -1.00; I2=95%; P<.001), pain-related fear using the Tampa Scale of Kinesiophobia (MD -5.46; 95% CI -9.40 to 1.52; I2=90%; P=.007), and disability using the Oswestry Disability Index (MD -11.50; 95% CI -20.00 to -3.01; I2=95%; P=.008) in individuals with chronic low back pain immediately after interventions. However, there were no significant differences observed in pain (P=.16), pain-related fear (P=.10), and disability (P=.43) in the short term. These findings indicated that virtual reality-based training can be used effectively for individuals with chronic low back pain in the immediate term, especially to reduce pain, alleviate pain-related fear, and improve disability. However, the short-term benefits need more high-quality trials to be demonstrated. PROSPERO CRD42021292633; http://tinyurl.com/25mydxpz.

GRADE pearls and pitfalls-Part 2: Clinical practice guidelines.

The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach is the de facto standard framework for summarising evidence in systematic reviews and developing recommendations in clinical practice guidelines. We describe how the GRADE approach is used in clinical practice guidelines, including key points and examples. The intended audience of this overview of GRADE is clinicians and researchers who are, or plan to be, involved in the development or assessment of clinical practice guidelines. We cover guideline endorsement and adaptation; guideline panels and sponsors; conflicts of interest; guideline questions and outcome prioritisation; systematic review creation, updating and re-use; rating the overall certainty of evidence; development of recommendations and implications; and peer review, publication, implementation and updating of guidelines. This overview aims to help developers, assessors and users of clinical practice guidelines understand how trustworthy, high-quality guidelines are developed using the GRADE approach.

The Effectiveness of Digital Health Lifestyle Interventions on People With Prediabetes: Protocol for a Systematic Review, Meta-Analysis, and Meta-Regression.

There has been an increasing interest in the use of digital health lifestyle interventions for people with prediabetes, as these interventions may offer a scalable approach to preventing type 2 diabetes. Previous systematic reviews on digital health lifestyle interventions for people with prediabetes had limitations, such as a narrow focus on certain types of interventions, a lack of statistical pooling, and no broader subgroup analysis of intervention characteristics. The identified limitations observed in previous systematic reviews substantiate the necessity of conducting a comprehensive review to address these gaps within the field. This will enable a comprehensive understanding of the effectiveness of digital health lifestyle interventions for people with prediabetes. The objective of this systematic review, meta-analysis, and meta-regression is to systematically investigate the effectiveness of digital health lifestyle interventions on prediabetes-related outcomes in comparison with any comparator without a digital component among adults with prediabetes. This systematic review will include randomized controlled trials that investigate the effectiveness of digital health lifestyle interventions on adults (aged 18 years or older) with prediabetes and compare the digital interventions with nondigital interventions. The primary outcome will be change in body weight (kg). Secondary outcomes include, among others, change in glycemic status, markers of cardiometabolic health, feasibility outcomes, and incidence of type 2 diabetes. Embase, PubMed, CINAHL, and CENTRAL (Cochrane Central Register of Controlled Trials) will be systematically searched. The data items to be extracted include study characteristics, participant characteristics, intervention characteristics, and relevant outcomes. To estimate the overall effect size, a meta-analysis will be conducted using the mean difference. Additionally, if feasible, meta-regression on study, intervention, and participant characteristics will be performed. The Cochrane risk of bias tool will be applied to assess study quality, and the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach will be used to assess the certainty of evidence. The results are projected to yield an overall estimate of the effectiveness of digital health lifestyle interventions on adults with prediabetes and elucidate the characteristics that contribute to their effectiveness. The insights gained from this study may help clarify the potential of digital health lifestyle interventions for people with prediabetes and guide the decision-making regarding future intervention components. PROSPERO CRD42023426919; http://tinyurl.com/d3enrw9j. PRR1-10.2196/50340.

Efficacy and Safety of Fezolinetant for the Treatment of Menopause-Associated Vasomotor Symptoms: A Meta-analysis.

To evaluate the efficacy and adverse events of fezolinetant for treating vasomotor symptoms (VMS) of menopause. PubMed/MEDLINE, ClinicalTrials.gov , EMBASE, Cochrane Database, Scopus, and WHO International Clinical Trials Registry Platform were searched through June 2023 for publications and randomized controlled trials on fezolinetant compared with placebo in menopausal women who experienced moderate-to-severe VMS. Our literature search identified 330 articles, of which five studies with six reports were included in our meta-analysis per our eligibility criteria. The risk of bias was evaluated using Cochrane's RoB 2 (Risk of Bias version 2) tool, quality of evidence was graded using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach, and outcome measures data for effect size were pooled in random-effects model and rated. A total of 2,168 participants from five randomized clinical trials (six reports) were included. Fezolinetant significantly lowered VMS frequency, with pooled mean difference of 2.62 (95% CI, 1.84-3.41). The pooled mean difference for fezolinetant compared with placebo for the MENQOL (Menopause-Specific Quality of Life) measure was -0.60 (95% CI, -0.92 to -0.28), and the mean percentage improvement in VMS frequency was 22.51% (95% CI, 15.35-29.67). Fezolinetant was associated with improvement in sleep quality when compared with placebo. Fezolinetant is effective in lowering moderate-to-severe VMS frequency and sleep disturbances in postmenopausal women. PROSPERO, CRD42023427616.

Does brain entrainment using binaural auditory beats affect pain perception in acute and chronic pain?: a systematic review

BackgroundPain is a major clinical problem across all ages with serious social and economic consequences and a great negative impact on quality of life. Brain entrainment using binaural beats is a non-pharmaceutical intervention that is claimed to have analgesic effects in acute and chronic pain. We aimed to systematically review the available randomized clinical trials on the efficacy of binaural auditory beats in reducing adults’ pain perception in acute and chronic pain. A systematic search in electronic databases including Medline (via PubMed), Web of Science, Scopus, Cochrane Central Register of Controlled Trials (CENTRAL), and Embase was performed. The search was completed through Google Scholar and a manual search of the reference lists of all included studies. Randomized clinical trials with full text available in English that investigated the effect of binaural auditory beats on pain perception in acute and chronic pain in adults were included. The risk of bias was assessed by the revised Cochrane risk-of-bias (RoB 2) tool. Furthermore, The GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach was used to assess the quality of the evidence. Sixteen studies (three on chronic pain and thirteen on acute pain perception) fulfilled the eligibility criteria. Because of substantial heterogeneity of the studies, a meta-analysis was inappropriate and this review focused on the narrative interpretation of the results. The risk of bias in most studies was high and the quality of evidence was low to very low. Although the effects of binaural beats on pain perception seem to be influenced by the etiology of pain or medical procedures, our review identifies alpha or a combination of tones in the range of delta to alpha as a potential non-pharmacological intervention in reducing acute pain. However, drawing a conclusion regarding the efficacy of binaural beats for chronic pain requires more high-quality studies.RegistrationThe protocol of this review was registered in PROSPERO (No. CRD42023425091).

Screening for hypertension in adults: protocol for evidence reviews to inform a Canadian Task Force on Preventive Health Care guideline update

PurposeTo inform updated recommendations by the Canadian Task Force on Preventive Health Care on screening in a primary care setting for hypertension in adults aged 18 years and older. This protocol outlines the scope and methods for a series of systematic reviews and one overview of reviews.MethodsTo evaluate the benefits and harms of screening for hypertension, the Task Force will rely on the relevant key questions from the 2021 United States Preventive Services Task Force systematic review. In addition, a series of reviews will be conducted to identify, appraise, and synthesize the evidence on (1) the association of blood pressure measurement methods and future cardiovascular (CVD)-related outcomes, (2) thresholds for discussions of treatment initiation, and (3) patient acceptability of hypertension screening methods. For the review of blood pressure measurement methods and future CVD-related outcomes, we will perform a de novo review and search MEDLINE, Embase, CENTRAL, and APA PsycInfo for randomized controlled trials, prospective or retrospective cohort studies, nested case–control studies, and within-arm analyses of intervention studies. For the thresholds for discussions of treatment initiation review, we will perform an overview of reviews and update results from a relevant 2019 UK NICE review. We will search MEDLINE, Embase, APA PsycInfo, and Epistemonikos for systematic reviews. For the acceptability review, we will perform a de novo systematic review and search MEDLINE, Embase, and APA PsycInfo for randomized controlled trials, controlled clinical trials, and observational studies with comparison groups. Websites of relevant organizations, gray literature sources, and the reference lists of included studies and reviews will be hand-searched. Title and abstract screening will be completed by two independent reviewers. Full-text screening, data extraction, risk-of-bias assessment, and GRADE (Grading of Recommendations Assessment, Development and Evaluation) will be completed independently by two reviewers. Results from included studies will be synthesized narratively and pooled via meta-analysis when appropriate. The GRADE approach will be used to assess the certainty of evidence for outcomes.DiscussionThe results of the evidence reviews will be used to inform Canadian recommendations on screening for hypertension in adults aged 18 years and older.Systematic review registrationThis protocol is registered on PROSPERO and is available on the Open Science Framework (osf.io/8w4tz).

A brief overview of the GRADE approach for rating strength of evidence and practice recommendations

The medical fraternity is faced with an avalanche of medical literature. While it is desirable that the current best evidence inform practice guidelines and recommendations, it is true that much of the evidence is not of optimal quality, and recommendations based on poor quality evidence may result in undesirable outcomes. Moreover, many context specific considerations, such as costs and patient preferences may be key concerns in formulating recommendations. These issues call for a systematic framework to rate the quality of evidence and strength of recommendations. The GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) offers such a framework for any given clinical question, and offers advantages over traditional approaches to guideline development. Crucial elements for ensuring the trustworthiness of the guideline development process, such as recruiting an appropriate panel, excluding conflicts of interest, systematically reviewing the best evidence, rating certainty in evidence, and incorporating patient values and preferences, are rendered due importance in the process.

Clinical practice guideline on the use of single-operator cholangioscopy in the diagnosis of indeterminate biliary stricture and the treatment of difficult biliary stones

Background and aimsSingle-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.MethodsACED 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.ResultsThe 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.ConclusionFor 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.

Treatments for Trauma-Induced Coagulopathy: Protocol for a Systematic Review and Meta-Analysis.

Trauma-induced coagulopathy (TIC) is a common and potentially life-threatening coagulopathy as a result of traumatic injury, characterized by abnormal blood clotting and bleeding. Although several treatments have been proposed for TIC, their effectiveness and safety remain unclear. Further, numerous systematic reviews and meta-analyses on trauma have been conducted; however, to our knowledge, there is no systematic review and meta-analysis that specifically focuses on TIC management. Therefore, a comprehensive synthesis of the available evidence on interventions for TIC is needed. This systematic review and meta-analysis aim to evaluate the effectiveness and safety of interventions for the management of TIC. We will conduct a systematic review and meta-analysis of randomized and nonrandomized controlled trials as well as observational studies regarding severe trauma in patients with TIC. The interventions will include administration of coagulation factor concentrates, tranexamic acid, and blood component products. The control group will be managed with an ordinal transfusion or administered placebo. The primary outcome will be in-hospital mortality. We will search the electronic databases of MEDLINE (PubMed), Web of Science, and the Cochrane Central Register of Controlled Trials. Two reviewers will independently screen the titles and abstracts, retrieve the full text of the selected articles, and extract essential data. We will apply uniform criteria for evaluating the risk of bias associated with individual randomized controlled trials and nonrandomized trials based on the Cochrane risk-of-bias tool. Risk ratio values will be expressed as point estimates with 95% CIs. Continuous variables will be expressed as the mean difference along with their 95% CIs and P values. We will assess the strength of evidence using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach. This review will be the first systematic review and meta-analysis providing information on the effectiveness and safety of interventions for the management of TIC, including the administration of coagulation factor concentrates, tranexamic acid, and blood component products. Ethics approval and patient consent were not required for this study protocol, as we conducted a systematic review and meta-analysis of publicly available data, without any direct involvement of human participants. We will summarize the selection of the eligible studies using a PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) flowchart. The results will be presented in a table summarizing the evidence. The results of the meta-analysis will be depicted using figures and forest plots. This systematic review will provide updated information on the efficacy and safety of using coagulation factor concentrates, tranexamic acid, and blood component products for patients with TIC. To our knowledge, there is no systematic review and meta-analysis that specifically focuses on treatments for TIC. UMIN registry UMIN000050170; https://tinyurl.com/yr8pcrj6. DERR1-10.2196/49582.

Systematic review and meta-analysis on the efficacy and safety of Injectable Lentinan combined with chemotherapy in the treatment of gastric cancer

BackgroundThis study employed a meta-analysis to evaluate the efficacy and safety of adjunctive treatment with injectable Lentinan (LNT) in combination with chemotherapy for gastric cancer (GC). MethodsComputer-based searches of 6 databases were performed to identify randomized controlled trials (RCTs) relevant to the treatment of GC with LNT through mid-March 2023. Two independent researchers performed risk of bias assessment and trial sequential analysis(TSA), extracted the data and used Revman 5.3 software for data analysis. The certainty of evidence was graded based on the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. ResultsA total of 31 RCTs with 2729 patients were included in the analysis. The results revealed that adjunctive therapy with LNT was associated with improved treatment efficacy (RR = 1.48, 95%CI: 1.36 ∼ 1.61, p < 0.00001), improvement in clusters of differentiation (CD3+, CD4+, and CD4+/CD8+), natural killer (NK) cells, and quality of life assessment (RR = 1.32, 95%CI: 1.20 ∼ 1.45, p < 0.00001) compared to using chemotherapy alone. In addition, there was a reduction in CD8+ levels, incidence of white blood cell decline, gastrointestinal reactions, and platelet decline. TSA results indicated that there was sufficient evidence to draw firm conclusions about these outcomes, and the GRADE scores showed ‘high’ or ‘moderate’ quality of evidence for these outcomes. ConclusionThe efficacy of treatment of GC with LNT in combination with chemotherapy was found to be better than chemotherapy alone. And no serious adverse effects were observed. However, further RCTs are needed to further validate the results of this study.

Prevention, Diagnosis, Evaluation, and Treatment of Hepatitis C in Chronic Kidney Disease: Synopsis of the Kidney Disease: Improving Global Outcomes 2022 Clinical Practice Guideline.

The Kidney Disease: Improving Global Outcomes (KDIGO) 2022 clinical practice guideline on prevention, diagnosis, evaluation, and treatment of hepatitis C in chronic kidney disease (CKD) is an update of the 2018 guideline from KDIGO. The KDIGO Work Group (WG) updated the guideline, which included reviewing and grading new evidence that was identified and summarized. As in the previous guideline, the WG used the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach to appraise evidence and rate the strength of recommendations and used expert judgment to develop recommendations. New evidence led to updating of recommendations in the chapters on treatment of hepatitis C virus (HCV) infection in patients with CKD (Chapter 2), management of HCV infection before and after kidney transplant (Chapter 4), and diagnosis and management of kidney disease associated with HCV infection (Chapter 5). Recommendations in chapters on detection and evaluation of hepatitis C in CKD (Chapter 1) and prevention of HCV transmission in hemodialysis units (Chapter 3) were not updated because of an absence of significant new evidence. The 2022 updated guideline includes 43 graded recommendations and 20 ungraded recommendations, 7 of which are new or modified on the basis of the most recent evidence and consensus among the WG members. The updated guidelines recommend expanding treatment of hepatitis C with sofosbuvir-based regimens to patients with CKD glomerular filtration rate categories G4 and G5, including those receiving dialysis; expanding the donor pool for kidney transplant recipients by accepting HCV-positive kidneys regardless of the recipient's HCV status; and initiating direct-acting antiviral treatment of HCV-infected patients with clinical evidence of glomerulonephritis without requiring kidney biopsy. The update also addresses the use of immunosuppressive regimens in such patients.

How do network meta-analyses address intransitivity when assessing certainty of evidence: a systematic survey

ObjectivesTo describe how systematic reviews with network meta-analyses (NMAs) that used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) NMA approach addressed intransitivity when assessing certainty of evidence.DesignSystematic survey.Data...

Efficacy and Tolerability of Gefapixant for Treatment of Refractory or Unexplained Chronic Cough

Gefapixant represents an emerging therapy for patients with refractory or unexplained chronic cough. To evaluate the efficacy and tolerability of gefapixant for the treatment of adults with refractory or unexplained chronic cough. MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and Web of Science from November 2014 to July 2023. Two reviewers independently screened for parallel and crossover randomized clinical trials (RCTs) that compared, in patients with refractory or unexplained chronic cough, either gefapixant with placebo, or 2 or more doses of gefapixant with or without placebo. Two reviewers independently extracted data. A frequentist random-effects dose-response meta-analysis or pairwise meta-analysis was used for each outcome. The GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach was used to rate the certainty in whether patients would perceive the effects as important (greater than the minimal important difference [MID]) or small (less than the MID). Cough frequency (measured using the VitaloJAK cough monitor; MID, 20%), cough severity (measured using the 100-mm visual analog scale [VAS]; higher score is worse; MID, 30 mm), cough-specific quality of life (measured using the Leicester Cough Questionnaire [LCQ]; score range, 3 [maximal impairment] to 21 [no impairment]; MID, 1.3 points), treatment-related adverse events, adverse events leading to discontinuation, and taste-related adverse events. Nine RCTs including 2980 patients were included in the primary analysis. Compared with placebo, gefapixant (45 mg twice daily) had small effects on awake cough frequency (17.6% reduction [95% CI, 10.6%-24.0%], moderate certainty), cough severity on the 100-mm VAS (mean difference, -6.2 mm [95% CI, -4.1 to -8.4]; high certainty), and cough-specific quality of life on the LCQ (mean difference, 1.0 points [95% CI, 0.7-1.4]; moderate certainty). Compared with placebo, gefapixant (45 mg twice daily) probably caused an important increase in treatment-related adverse events (32 more per 100 patients [95% CI, 13-64 more], moderate certainty) and taste-related adverse events (32 more per 100 patients [95% CI, 22-46 more], high certainty). High-certainty evidence suggests that gefapixant (15 mg twice daily) had small effects on taste-related adverse events (6 more per 100 patients [95% CI, 5-8 more]). Compared with placebo, gefapixant (45 mg orally twice daily) led to modest improvements in cough frequency, cough severity, and cough-specific quality of life but increased taste-related adverse events.

European Respiratory Society short guidelines for the use of as-needed ICS/formoterol in mild asthma.

Recent clinical trials of as-needed fixed-dose combination of inhaled corticosteroid (ICS)/formoterol have provided new evidence that may warrant a reconsideration of current practice. A Task Force was set up by the European Respiratory Society to provide evidence-based recommendations on the use of as-needed ICS/formoterol as treatment for mild asthma. The Task Force defined two questions that were assessed using the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach. The Task Force utilised the outcomes to develop recommendations for a pragmatic guideline for everyday clinical practice. The Task Force suggests that adults with mild asthma use as-needed ICS/formoterol instead of regular ICS maintenance treatment plus as-needed short-acting β2-antagonist (SABA) and that adolescents with mild asthma use either as-needed ICS/formoterol or ICS maintenance treatment plus as-needed SABA (conditional recommendation; low certainty of evidence). The recommendation for adults places a relatively higher value on the reduction of systemic corticosteroid use and the outcomes related to exacerbations, and a relatively lower value on the small differences in asthma control. Either treatment option is suggested for adolescent patients as the balance is very close and data more limited. The Task Force recommends that adult and adolescent patients with mild asthma use as-needed ICS/formoterol instead of as-needed SABA (strong recommendation; low certainty of evidence). This recommendation is based on the benefit of as-needed ICS/formoterol in mild asthma on several outcomes and the risks related to as-needed SABA in the absence of anti-inflammatory treatment. The implementation of this recommendation is hampered in countries (including European Union countries) where as-needed ICS/formoterol is not approved for mild asthma.

The effects of Quercetin supplementation on cardiometabolic outcomes: An umbrella review of meta-analyses of randomized controlled trials.

Quercetin is a bioactive flavonoid, but the effect of it on cardiometabolic factors has remained uncertain and previous findings from meta-analyses have been controversial. To provide an overview of the effects of Quercetin on cardiometabolic factors based on meta-analyses of randomized controlled trials (RCTs). MEDLINE, SciVerse Scopus, and Clarivate Analytics Web of Science databases were searched to identify eligible publications. As part of the umbrella review, we summarized pooled estimates, 95% CIs, heterogeneity, and publication bias. A GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach was used to rate the certainty of evidence. Five meta-analyses including 18 eligible RCTs plus 5 RCTs that were not included in previous meta-analyses were found. The results indicated Quercetin does not affect diastolic blood pressure (DBP), lipid profile, inflammation, anthropometric indices, fasting plasma glucose (FBG), and homeostatic model assessment for insulin resistance (HOMA-IR). However, Quercetin supplementation could significantly reduce systolic blood pressure (SBP) (weighted mean difference (WMD): -1.9, 95% CI = -3.2 to -0.6, I2 = 88.3%) and insulin level (WMD: -1.07, 95% CI = -1.9 to -0.1, I2 = 75.0%). The certainty of evidence ranged from very low to moderate. Quercetin supplementation has reducing effects on SBP and insulin levels but not other cardiometabolic parameters. More high-quality trials with longer follow-up durations may be required to obtain a more robust conclusion.

Incisional negative pressure wound therapy for the prevention of surgical site infection: an up-to-date meta-analysis and trial sequential analysis

The evidence on prophylactic use of negative pressure wound therapy on primary closed incisional wounds (iNPWT) for the prevention of surgical site infections (SSI) is confusing and ambiguous. Implementation in daily practice is impaired by inconsistent recommendations in current international guidelines and published meta-analyses. More recently, multiple new randomised controlled trials (RCTs) have been published. We aimed to provide an overview of all meta-analyses and their characteristics; to conduct a new and up-to-date systematic review and meta-analysis and Grading of Recommendations Assessment, Development and Evaluation (GRADE) assessment; and to explore the additive value of new RCTs with a trial sequential analysis (TSA). PubMed, Embase and Cochrane CENTRAL databases were searched from database inception to October 24, 2022. We identified existing meta-analyses covering all surgical specialties and RCTs studying the effect of iNPWT compared with standard dressings in all types of surgery on the incidence of SSI, wound dehiscence, reoperation, seroma, hematoma, mortality, readmission rate, skin blistering, skin necrosis, pain, and adverse effects of the intervention. We calculated relative risks (RR) with corresponding 95% confidence intervals (CI) using a Mantel-Haenszel random-effects model. We assessed publication bias with a comparison-adjusted funnel plot. TSA was used to assess the risk of random error. The certainty of evidence was evaluated using the Cochrane Risk of Bias-2 (RoB2) tool and GRADE approach. This study is registered with PROSPERO, CRD42022312995. We identified eight previously published general meta-analyses investigating iNPWT and compared their results to present meta-analysis. For the updated systematic review, 57 RCTs with 13,744 patients were included in the quantitative analysis for SSI, yielding a RR of 0.67 (95% CI: 0.59-0.76, I2=21%) for iNPWT compared with standard dressing. Certainty of evidence was high. Compared with previous meta-analyses, the RR stabilised, and the confidence interval narrowed. In the TSA, the cumulative Z-curve crossed the trial sequential monitoring boundary for benefit, confirming the robustness of the summary effect estimate from the meta-analysis. In this up-to-date meta-analysis, GRADE assessment shows high-certainty evidence that iNPWT is effective in reducing SSI, and uncertainty is less than in previous meta-analyses. TSA indicated that further trials are unlikely to change the effect estimate for the outcome SSI; therefore, if future research is to be conducted on iNPWT, it is crucial to consider what the findings will contribute to the existing robust evidence. Dutch Association for Quality Funds Medical Specialists.