An exploratory descriptive survey on the use of GRADE and CINeMA: time-consuming, process transparency and subjectivity vs high-speed, practical challenges, and poor understanding.

Grading of Recommendations Assessment, Development, and Evaluation and Confidence in Network Meta-Analysis showed moderate to substantial concordance in the evaluation of certainty of the evidence.

ObjectivesAssessment of the certainty of evidence (CoE) from network meta-analysis is critical to convey the strength of inferences for clinical decision-making. Both the GRADE (Grading of Recommendations Assessment, Development and Evaluation) Working Group (GWG) and the Confidence in Network Meta-Analysis (CINeMA) framework have been designed to assess the CoE of treatment effects informed by network meta-analysis; however, the concordance of results is uncertain. Study Design and SettingWe assessed the CoE for treatment effects of individual opioids on pain relief and physical functioning from a network meta-analysis for chronic noncancer pain using the GWG approach and the CINeMA framework. Both approaches evaluate the CoE as high, moderate, low or very low. We quantified the number of discrepant CoE ratings between approaches and the magnitude of the difference (ie, one level, two levels, or three levels). ResultsAcross 105 comparisons among individual opioids for pain relief, the GWG and CINeMA approaches provided different CoE ratings in 34% of cases (36 of 105). Across 66 comparisons for physical functioning, there was discordance in 17% of cases (11 of 66). All discrepancies were separated by one level. The CINeMA framework typically provided lower CoE ratings compared to the GWG approach, predominantly because of differences in the assessment of transitivity and heterogeneity. ConclusionOur findings suggest there are differences between the CoE ratings provided by the GWG and CINeMA approaches when applied to network meta-analyses. Further research is needed to replicate or refute our findings in other network meta-analyses and assess the implications for clinical decision-making.

Deferred cord clamping and cord milking: Certainty and quality of the evidence in meta-analyses, and systematic reviews of randomized control trials, guidelines, and implementation studies

Haemorrhoidal disease affects 25-40% of adults worldwide and constitutes a primary reason for outpatient colorectal consultations. Surgical management is essential for grade III-IV or treatment-refractory cases. Numerous procedures have emerged, including Milligan-Morgan open haemorrhoidectomy, Ferguson closed haemorrhoidectomy, stapled haemorrhoidopexy, Doppler-guided haemorrhoidal artery ligation, transanal haemorrhoidal dearterialisation and laser haemorrhoidoplasty. However, randomised controlled trials and conventional meta-analyses report conflicting results on efficacy, postoperative pain, recurrence rates and complications such as bleeding, stenosis and incontinence. Although network meta-analyses exist, an updated synthesis is needed because outcomes and follow-up vary across trials. This protocol aims to determine the most effective and safest haemorrhoid interventions (office-based and operative) through systematic review and network meta-analysis, providing evidence-based guidance for clinical practice and guideline development. The Cochrane Library, Web of Science, MEDLINE, Embase, China National Knowledge Infrastructure, VIP, SinoMed and Wanfang databases will be searched from inception to January 2025, limited to English or Chinese publications. Randomised controlled trials evaluating haemorrhoid interventions/procedures for haemorrhoidal disease will be included, with outcomes encompassing cure rate, recurrence, complications, postoperative pain, wound-healing time, anal function and operative duration. Risk of bias will be assessed using RoB 2. Pairwise meta-analyses will be conducted in RevMan; network meta-analysis will employ Bayesian frameworks in GeMTC or R, incorporating consistency evaluation, node-splitting and surface under the cumulative ranking curve for treatment ranking. Subgroup analyses (haemorrhoid grade, follow-up duration), sensitivity analyses and publication bias assessments will be performed. Evidence certainty will be graded using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach and the Confidence in Network Meta-Analysis (CINeMA) framework. As only published data will be used, ethical approval is not required. Results will be disseminated via peer-reviewed publication and conference presentations. CRD420251053697.

ObjectiveTo assess whether relaxation and stress management techniques are useful in reducing blood pressure in individuals with hypertension and prehypertension.DesignSystematic review and network meta-analysis.Data sourcesMedline, PsycInfo, and CENTRAL (Cochrane Central...

Parkinson's disease is a neurological disease with a rising incidence and prevalence. Patients with Parkinson's disease may receive antipsychotics, for example, due to Parkinson's disease psychosis. Parkinson's disease psychosis is characterised by visual hallucinations and other psychotic symptoms. To date, no systematic review has evaluated the effects of antipsychotics in patients with Parkinson's disease. Therefore, this review aims to assess the beneficial and harmful effects of antipsychotics for Parkinson's disease. This is a protocol for a systematic review. A search specialist will perform a search in major medical databases (eg, MEDLINE (Medical Literature Analysis and Retrieval System Online), EMBASE (Excerpta Medica database), CENTRAL (Cochrane Central Register of Controlled Trials)) and clinical trial registries. Published and unpublished randomised clinical trials comparing antipsychotics to any control (placebo, standard care or other antipsychotics) in patients with Parkinson's disease will be included. Two review authors will independently extract data and conduct risk of bias assessments with the Cochrane Risk of Bias tool-V.2. Primary outcomes will be all-cause mortality, serious adverse events and significant falls. Secondary outcomes will be hospitalisations, non-serious adverse events, Unified Parkinson's Disease Rating Scale total score and psychotic symptoms using any valid symptom scale. Data will be synthesised by aggregate meta-analysis, trial sequential analysis and network meta-analysis. Several subgroup analyses are planned. An eight-step procedure will be used to assess if the thresholds for clinical significance are crossed, and the certainty of the evidence will be assessed by GRADE (Grading of Recommendations Assessment, Development and Evaluations) and CiNeMA (Confidence in Network Meta-Analysis) approach. This protocol does not include results, and ethics approval is not required for the project. The findings from the systematic review will be published in international peer-reviewed scientific journals. PROSPERO ID: CRD42025633985. Available from https://www.crd.york.ac.uk/PROSPERO/view/CRD42025633985.

BackgroundThe evaluation of imprecision is a key dimension of the grading of the confidence in the estimate. Grading of Recommendations Assessment, Development and Evaluation (GRADE) gives recommendations on how to downgrade evidence for imprecision, but authors vary in their use. Trial Sequential Analysis (TSA) has been advocated for a more reliable assessment of imprecision. We aimed to evaluate reporting of and adherence to GRADE and to compare the assessment of imprecision of intervention effects assessed by GRADE and TSA in Cochrane systematic reviews.MethodsIn this cross-sectional study, we included 100 Cochrane reviews irrespective of type of intervention with a key dichotomous outcome meta-analyzed and assessed by GRADE. The methods and results sections of each review were assessed for adequacy of imprecision evaluation. We re-analyzed imprecision following the GRADE Handbook and the TSA Manual.ResultsOverall, only 13.0% of reviews stated the criteria they applied to assess imprecision. The most common dimensions were the 95% width of the confidence intervals and the optimal information size. Review authors downgraded 48.0% of key outcomes due to imprecision. When imprecision was re-analyzed following the GRADE Handbook, 64% of outcomes were downgraded. Agreement between review authors’ assessment and assessment by the authors of this study was moderate (kappa 0.43, 95% confidence interval [CI] 0.23 to 0.58). TSA downgraded 69.0% outcomes due to imprecision. Agreement between review authors’ GRADE assessment and TSA, irrespective of downgrading levels, was moderate (kappa 0.43, 95% CI 0.21 to 0.57). Agreement between our GRADE assessment following the Handbook and TSA was substantial (kappa 0.66, 95% CI 0.49 to 0.79).ConclusionsIn a sample of Cochrane reviews, methods for assessing imprecision were rarely reported. GRADE according to Handbook guidelines and TSA led to more severe judgment of imprecision rather than GRADE adopted by reviews’ authors. Cochrane initiatives to improve adherence to GRADE Handbook are warranted. TSA may transparently assist in such development.

IntroductionFor major depression, a one-size-fits-all treatment does not exist. Patients enter a ‘trial-and-change’ algorithm in which effective therapies are subsequently applied. Unfortunately, an empirically based order of treatments has not...

This systematic review provides supporting evidence for the accompanying clinical practice guideline on the treatment of central disorders of hypersomnolence in adults and children. The review focuses on prescription medications with U.S. Food & Drug Administration approval and nonpharmacologic interventions studied for the treatment of symptoms caused by central disorders of hypersomnolence. The American Academy of Sleep Medicine commissioned a task force of experts in sleep medicine to perform a systematic review. Randomized controlled trials and observational studies addressing pharmacological and nonpharmacological interventions for central disorders of hypersomnolence were identified. Statistical analyses were performed to determine the clinical significance of all outcomes. Finally, the Grading of Recommendations Assessment, Development and Evaluation (GRADE) process was used to assess the evidence for the purpose of making specific treatment recommendations. The literature search identified 678 studies; 144 met the inclusion criteria and 108 provided data suitable for statistical analyses. Evidence for the following interventions is presented: armodafinil, clarithromycin, clomipramine, dextroamphetamine, flumazenil, intravenous immune globulin (IVIG), light therapy, lithium, l-carnitine, liraglutide, methylphenidate, methylprednisolone, modafinil, naps, pitolisant, selegiline, sodium oxybate, solriamfetol, and triazolam. The task force provided a detailed summary of the evidence along with the quality of evidence, the balance of benefits and harms, patient values and preferences, and resource use considerations. Maski K, Trotti LM, Kotagal S, etal. Treatment of central disorders of hypersomnolence: an American Academy of Sleep Medicine systematic review, meta-analysis, and GRADE assessment. J Clin Sleep Med. 2021;17(9):1895-1945.

Background There are currently no sex-specific recommendations for antipsychotic prescribing in schizophrenia, although women may be more susceptible to certain side-effects and may require lower doses to achieve comparable efficacy to men. However, sex differences remain insufficiently studied to inform treatment decisions. Methods We plan a systematic review and individual-participant-data meta-analysis of randomized trials comparing different antipsychotic drugs, doses, formulations with each other or with placebo in adults with acute schizophrenia. Eligible studies will be identified through the Vivli platform, and their individual-participant-data will be harmonized into a common dataset. Two independent reviewers will screen search results and assess risk of bias using the Risk of Bias 2 tool. The primary outcome will be overall symptoms of schizophrenia, and secondary outcomes will include a broad range of efficacy, tolerability, acceptability, and dosing measures. A stepwise approach to data synthesis will be adopted, depending on individual-participant-data availability, aiming to examine sex differences in the effects of antipsychotic drugs compared to placebo. If sufficient data are available, we will conduct random-effects meta-analyses using regression models to evaluate biological sex, typically categorised as male or female, as both a prognostic factor and an effect modifier, network meta-analyses to synthesize direct and indirect evidence, and dose-response meta-analyses using restricted cubic splines to explore dose-effect relationships. The robustness of the findings will be assessed through sensitivity analyses adjusting for additional covariates. The certainty of evidence on sex differences will be evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach for subgroup analysis. If the certainty is judged to be moderate or high, sex-specific treatment effects will be further assessed using the Confidence in Network Meta-Analysis (CINeMA) framework. Discussion This study will examine sex differences in the efficacy, tolerability, and dosing of antipsychotics in acute schizophrenia, potentially contributing to evidence-based, sex-specific treatment recommendations for antipsychotic prescribing. Protocol registration PROSPERO-ID: CRD420251022957

BackgroundNumerous trials confirm dietary interventions benefit type 2 diabetes mellitus (T2DM) management, but the optimal model is unclear. We evaluated 12 interventions through a Network Meta-Analysis (NMA) on their effects on Fasting Plasma Glucose (FPG), 2-h Postprandial Glucose (2hPG), HbA1c, Homeostasis Model Assessment of Insulin Resistance (HOMA-IR), Total Cholesterol (TC), Triglycerides (TG), and BMI, providing evidence to guide clinical nursing.MethodsWe conducted an NMA of randomized controlled trials (RCTs) (PROSPERO registration: CRD42023429616), searching eight databases for studies published between January 1, 2010, and August 31, 2024. Two reviewers independently screened studies, extracted data, and assessed bias using the Cochrane Risk of Bias tool. Key and important outcomes were analyzed using Stata 17.0, with evidence quality assessed via the Grading of Recommendations Assessment, Development and Evaluation (GRADE) and Confidence in Network Meta-Analysis (CINeMA) scores.ResultsEighteen RCTs comprising 1,687 patients were included. Among 12 evaluated dietary interventions, MNT ranked highest in reducing FPG (SUCRA = 77.6%; SMD = -0.75; 95% CI: -0.88 to -0.61). Digital dietary models were most effective for reducing HbA1c (SUCRA = 84.6%; SMD = -1.06; 95% CI: -2.11 to -0.01), while LGI diets were superior for both 2hPG (SUCRA = 62.1%; SMD = -0.62; 95% CI: -0.76 to -0.47) and HOMA-IR (SUCRA = 96.9%; SMD = -10.13; 95% CI: -15.96 to -4.30). The LGI + LGL intervention was most effective in reducing TC (SUCRA = 88.3%), TG (SUCRA = 80.6%), and BMI (SUCRA = 99.8%), with statistically significant differences observed in pairwise comparisons (P < 0.05). The quality of evidence was rated as high for FPG, 2hPG, HbA1c, and BMI, and moderate for HOMA-IR, TC, and TG.ConclusionsThese findings highlight the potential of MNT, LGI, digital dietary models, and LGI + LGL interventions to improve glycemic control and metabolic outcomes in patients with T2DM. However, further large-scale, multicenter RCTs are warranted to validate their long-term efficacy and safety.Trial registrationCRD42023429616.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12986-025-00968-3.

There are currently no sex-specific recommendations for antipsychotic prescribing in schizophrenia, although women may be more susceptible to certain side-effects and may require lower doses to achieve comparable efficacy to men. However, sex differences remain insufficiently studied to inform treatment decisions. We plan a systematic review and individual-participant-data meta-analysis of randomized trials comparing different antipsychotic drugs, doses, formulations with each other or with placebo in adults with acute schizophrenia. Eligible studies will be identified through the Vivli platform, and their individual-participant-data will be harmonized into a common dataset. Two independent reviewers will screen search results and assess risk of bias using the Risk of Bias 2 tool. The primary outcome will be overall symptoms of schizophrenia, and secondary outcomes will include a broad range of efficacy, tolerability, acceptability, and dosing measures.A stepwise approach to data synthesis will be adopted, depending on individual-participant-data availability, aiming to examine sex differences in the effects of antipsychotic drugs compared to placebo. If sufficient data are available, we will conduct random-effects meta-analyses using regression models to evaluate biological sex, typically categorised as male or female, as both a prognostic factor and an effect modifier, network meta-analyses to synthesize direct and indirect evidence, and dose-response meta-analyses using restricted cubic splines to explore dose-effect relationships. The robustness of the findings will be assessed through sensitivity analyses adjusting for additional covariates.The certainty of evidence on sex differences will be evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach for subgroup analysis. If the certainty is judged to be moderate or high, sex-specific treatment effects will be further assessed using the Confidence in Network Meta-Analysis (CINeMA) framework. This study will examine sex differences in the efficacy, tolerability, and dosing of antipsychotics in acute schizophrenia, potentially contributing to evidence-based, sex-specific treatment recommendations for antipsychotic prescribing. Protocol registration PROSPERO-ID: CRD420251022957.

Background There are currently no sex-specific recommendations for antipsychotic prescribing in schizophrenia, although women may be more susceptible to certain side-effects and may require lower doses to achieve comparable efficacy to men. However, sex differences remain insufficiently studied to inform treatment decisions. Methods We plan a systematic review and individual-participant-data meta-analysis of randomized trials comparing different antipsychotic drugs, doses, formulations with each other or with placebo in adults with acute schizophrenia. Eligible studies will be identified through the Vivli platform, and their individual-participant-data will be harmonized into a common dataset. Two independent reviewers will screen search results and assess risk of bias using the Risk of Bias 2 tool. The primary outcome will be overall symptoms of schizophrenia, and secondary outcomes will include a broad range of efficacy, tolerability, acceptability, and dosing measures. A stepwise approach to data synthesis will be adopted, depending on individual-participant-data availability, aiming to examine sex differences in the effects of antipsychotic drugs compared to placebo. If sufficient data are available, we will conduct random-effects meta-analyses using regression models to evaluate biological sex, typically categorised as male or female, as both a prognostic factor and an effect modifier, network meta-analyses to synthesize direct and indirect evidence, and dose-response meta-analyses using restricted cubic splines to explore dose-effect relationships. The robustness of the findings will be assessed through sensitivity analyses adjusting for additional covariates. The certainty of evidence on sex differences will be evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach for subgroup analysis. If the certainty is judged to be moderate or high, sex-specific treatment effects will be further assessed using the Confidence in Network Meta-Analysis (CINeMA) framework. Discussion This study will examine sex differences in the efficacy, tolerability, and dosing of antipsychotics in acute schizophrenia, potentially contributing to evidence-based, sex-specific treatment recommendations for antipsychotic prescribing. Protocol registration PROSPERO-ID: CRD420251022957

Evidence Evaluation Process and Management of Potential Conflicts of Interest: 2020 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations.

Postoperative nausea and vomiting is a common adverse effect of anaesthesia. Although dozens of different anti-emetics are available for clinical practice, there is currently no comparative ranking of efficacy and safety of these drugs to inform clinical practice. We performed a systematic review with network meta-analyses to compare, and rank in terms of efficacy and safety, single anti-emetic drugs and their combinations, including 5-hydroxytryptamine3 , dopamine-2 and neurokinin-1 receptor antagonists; corticosteroids; antihistamines; and anticholinergics used to prevent postoperative nausea and vomiting in adults after general anaesthesia. We systematically searched for placebo-controlled and head-to-head randomised controlled trials up to November 2017 (updated in April 2020). We assessed how trustworthy the evidence was using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) and Confidence In Network Meta-Analysis (CINeMA) approaches for vomiting within 24h postoperatively, serious adverse events, any adverse event and drug class-specific side-effects. We included 585 trials (97,516 participants, 83% women) testing 44 single drugs and 51 drug combinations. The studies' overall risk of bias was assessed as low in only 27% of the studies. In 282 trials, 29 out of 36 drug combinations and 10 out of 28 single drugs lowered the risk of vomiting at least 20% compared with placebo. In the ranking of treatments, combinations of drugs were generally more effective than single drugs. Single neurokinin-1 receptor antagonists were as effective as other drug combinations. Out of the 10 effective single drugs, certainty of evidence was high for aprepitant, with risk ratio (95%CI) 0.26 (0.18-0.38); ramosetron, 0.44 (0.32-0.59); granisetron, 0.45 (0.38-0.54); dexamethasone, 0.51 (0.44-0.57); and ondansetron, 0.55 (0.51-0.60). It was moderate for fosaprepitant, 0.06 (0.02-0.21) and droperidol, 0.61 (0.54-0.69). Granisetron and amisulpride are likely to have little or no increase in any adverse event compared with placebo, while dimenhydrinate and scopolamine may increase the number of patients with any adverse event compared with placebo. So far, there is no convincing evidence that other single drugs effect the incidence of serious, or any, adverse events when compared with placebo. Among drug class specific side-effects, evidence for single drugs is mostly not convincing. There is convincing evidence regarding the prophylactic effect of at least seven single drugs for postoperative vomiting such that future studies investigating these drugs will probably not change the estimated beneficial effect. However, there is still considerable lack of evidence regarding safety aspects that does warrant investigation.