Pharmacological and non-pharmacological interventions for irritability in autism spectrum disorder: a systematic review and meta-analysis with the GRADE assessment.

BACKGROUND: Numerous interventions for irritability in autism spectrum disorder (ASD) have been investigated. We aimed to appraise the magnitude of pharmacological and non-pharmacological interventions for irritability in ASD without any restrictions in terms of eligible interventions. METHODS: We systematically searched PubMed/MEDLINE, Scopus, and Web of Science until April 15, 2023. We included randomized controlled trials (RCTs) with a parallel design that examined the efficacy of interventions for the treatment of irritability in patients of any age with ASD without any restrictions in terms of eligible interventions. We performed a random-effects meta-analysis by pooling effect sizes as Hedges' g. We classified assessed interventions as follows: pharmacological monotherapy, risperidone plus adjuvant therapy versus risperidone monotherapy, non-pharmacological intervention, and dietary intervention. We utilized the Cochrane tool to evaluate the risk of bias in each study and the GRADE approach to assess the certainty of evidence for each meta-analyzed intervention. RESULTS: Out of 5640 references, we identified 60 eligible articles with 45 different kinds of interventions, including 3531 participants, of which 80.9% were males (mean age [SD] = 8.79 [3.85]). For pharmacological monotherapy, risperidone (Hedges' g - 0.857, 95% CI - 1.263 to - 0.451, certainty of evidence: high) and aripiprazole (Hedges' g - 0.559, 95% CI - 0.767 to - 0.351, certainty of evidence: high) outperformed placebo. Among the non-pharmacological interventions, parent training (Hedges' g - 0.893, 95% CI - 1.184 to - 0.602, certainty of evidence: moderate) showed a significant result. None of the meta-analyzed interventions yielded significant effects among risperidone + adjuvant therapy and dietary supplementation. However, several novel molecules in augmentation to risperidone outperformed risperidone monotherapy, yet from one RCT each. LIMITATIONS: First, various tools have been utilized to measure the irritability in ASD, which may contribute to the heterogeneity of the outcomes. Second, meta-analyses for each intervention included only a small number of studies and participants. CONCLUSIONS: Only risperidone, aripiprazole among pharmacological interventions, and parent training among non-pharmacological interventions can be recommended for irritability in ASD. As an augmentation to risperidone, several novel treatments show promising effects, but further RCTs are needed to replicate findings. Trial registration PROSPERO, CRD42021243965.

Biopathologic Characterization and Grade Assessment of Breast Cancer With 3-D Multiparametric Ultrasound Combining Shear Wave Elastography and Backscatter Tensor Imaging.

OBJECTIVE: Despite recent improvements in medical imaging, the final diagnosis and biopathologic characterization of breast cancers currently still requires biopsies. Ultrasound is commonly used for clinical examination of breast masses. B-Mode and shear wave elastography (SWE) are already widely used to detect suspicious masses and differentiate benign lesions from cancers. But additional ultrasound modalities such as backscatter tensor imaging (BTI) could provide relevant biomarkers related to tissue organization. Here we describe a 3-D multiparametric ultrasound approach applied to breast carcinomas in the aims of (i) validating the ability of BTI to reveal the underlying organization of collagen fibers and (ii) assessing the complementarity of SWE and BTI to reveal biopathologic features of diagnostic interest. METHODS: Three-dimensional SWE and BTI were performed ex vivo on 64 human breast carcinoma samples using a linear ultrasound probe moved by a set of motors. Here we describe a 3-D multiparametric representation of the breast masses and quantitative measurements combining B-mode, SWE and BTI. RESULTS: Our results reveal for the first time that BTI can capture the orientation of the collagen fibers around tumors. BTI was found to be a relevant marker for assessing cancer stages, revealing a more tangent tissue orientation for in situ carcinomas than for invasive cancers. In invasive cases, the combination of BTI and SWE parameters allowed for classification of invasive tumors with respect to their grade with an accuracy of 95.7%. CONCLUSION: Our results highlight the potential of 3-D multiparametric ultrasound imaging for biopathologic characterization of breast tumors.

Effect of aquatic exercise programs according to the International Classification of Functionality, Disability and Health domains in individuals with Parkinson's disease: a systematic review and meta-analysis with GRADE quality assessment.

PURPOSE: To investigate the effects of aquatic exercise programs (AEP) in body structure and function, activity, and participation outcomes in individuals with Parkinson's disease (PD) with mild to moderate disability levels. METHODS: Six databases were searched from inception until November 2022. Randomized clinical trials that used AEP alone, AEP combined and/or compared two types of AEP were included. The quality of evidence was assessed by the GRADE approach and the standardized mean differences (SMD) were calculated the meta-analysis. RESULTS: Twelve studies (n = 380) were included. AEP alone was superior to active control in improving body structure and function outcome: postural balance (low evidence, SMD = 0.47, p = 0.02). No statistically significant differences were found for the other body structure and function outcomes: lower limb muscle strength (p = 0.14) and depressive symptoms (p = 0.79), activity outcomes: mobility (p = 0.32) and participation outcomes: quality of life (p = 0.05). AEP combined showed no statistically significant difference for the outcomes of body structure and function: postural balance (p = 0.11) and activity: mobility (p = 0.21) when compared to active control. CONCLUSION: AEP showed positive effects on body structure and function outcome (postural balance) in individuals with PD with mild to moderate disability levels while, no significant improvements were noticed for activity and participation outcomes.IMPLICATIONS FOR REHABILITATIONOur findings indicate that aquatic exercise programs (AEP) lead to significant improvements on body structure and function (i.e., postural balance) in individuals with Parkinson's disease (PD).The AEP evaluated in this study implemented postural balance, gait, single and double training, as well as aerobic exercises, trunk mobility exercises, and Ai Chi.The average duration, frequency, and total time implemented were 50 minutes, three times a week, for seven weeks, respectively.Considering the potential benefits identified in this study, AEP can be recommended as an adjunct treatment strategy for individuals with PD.Additionally, the use of the International Classification of Functionality, Disability and Health on the development of rehabilitation treatment plans is advised.

EAES Multidisciplinary Rapid Guideline: systematic review, meta-analysis, GRADE assessment and evidence-informed recommendations on the surgical management of paraesophageal hernias.

BACKGROUND: New evidence has emerged since latest guidelines on the management of paraesophageal hernia, and guideline development methodology has evolved. Members of the European Association for Endoscopic Surgery have prioritized the management of paraesophageal hernia to be addressed by pertinent recommendations. OBJECTIVE: To develop evidence-informed clinical practice recommendations on paraesophageal hernias, through evidence synthesis and a structured evidence-to-decision framework by an interdisciplinary panel of stakeholders. METHODS: We performed three systematic reviews, and we summarized and appraised the certainty of the evidence using the GRADE methodology. A panel of general and upper gastrointestinal surgeons, gastroenterologists and a patient advocate discussed the evidence in the context of benefits and harms, the certainty of the evidence, acceptability, feasibility, equity, cost and use of resources, moderated by a Guidelines International Network-certified master guideline developer and chair. We developed the recommendations in a consensus meeting, followed by a modified Delphi survey. RESULTS: The panel suggests surgery over conservative management for asymptomatic/minimally symptomatic paraesophageal hernias (conditional recommendation), and recommends conservative management over surgery for asymptomatic/minimally symptomatic paraesophageal hernias in frail patients (strong recommendation). Further, the panel suggests mesh over sutures for hiatal closure in paraesophageal hernia repair, fundoplication over gastropexy in elective paraesophageal hernia repair, and gastropexy over fundoplication in patients who have cardiopulmonary instability and require emergency paraesophageal hernia repair (conditional recommendation). A strong recommendation means that the proposed course of action is appropriate for the vast majority of patients. A conditional recommendation means that most patients would opt for the proposed course of action, and joint decision-making of the surgeon and the patient is required. Accompanying evidence summaries and evidence-to-decision frameworks should be read when using the recommendations. This guideline applies to adult patients with moderate to large paraesophageal hernias type II to IV with at least 50% of the stomach herniated to the thoracic cavity. The full guideline with user-friendly decision aids is available in https://app.magicapp.org/#/guideline/j7q7Gn . CONCLUSION: An interdisciplinary panel provides recommendations on key topics on the management of paraesophageal hernias using highest methodological standards and following a transparent process. GUIDELINE REGISTRATION NUMBER: PREPARE-2023CN018.

Standardized Classification of Lung Adenocarcinoma Subtypes and Improvement of Grading Assessment Through Deep Learning.

The histopathologic distinction of lung adenocarcinoma (LADC) subtypes is subject to high interobserver variability, which can compromise the optimal assessment of patient prognosis. Therefore, this study developed convolutional neural networks capable of distinguishing LADC subtypes and predicting disease-specific survival, according to the recently established LADC tumor grades. Consensus LADC histopathologic images were obtained from 17 expert pulmonary pathologists and one pathologist in training. Two deep learning models (AI-1 and AI-2) were trained to predict eight different LADC classes. Furthermore, the trained models were tested on an independent cohort of 133 patients. The models achieved high precision, recall, and F1 scores exceeding 0.90 for most of the LADC classes. Clear stratification of the three LADC grades was reached in predicting the disease-specific survival by the two models, with both Kaplan-Meier curves showing significance (P = 0.0017 and 0.0003). Moreover, both trained models showed high stability in the segmentation of each pair of predicted grades with low variation in the hazard ratio across 200 bootstrapped samples. These findings indicate that the trained convolutional neural networks improve the diagnostic accuracy of the pathologist and refine LADC grade assessment. Thus, the trained models are promising tools that may assist in the routine evaluation of LADC subtypes and grades in clinical practice.

GRADE guidance 23: considering cost-effectiveness evidence in moving from evidence to health-related recommendations.

BACKGROUND: This is the 23rd in a series of articles describing the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to grading the certainty of evidence and strength of recommendations for systematic reviews, health technology assessments, and clinical guideline development. OBJECTIVES: We outline how resource utilization and cost-effectiveness analyses are integrated into health-related recommendations, using the GRADE Evidence to Decision (EtD) frameworks. STUDY DESIGN AND SETTING: Through iterative discussions and refinement, in-person, and online meetings, and through e-mail communication, we developed draft guidance to incorporate economic evidence in the formulation of health-related recommendations. We developed scenarios to operationalize the guidance. We presented a summary of the results to members of the GRADE Economic Evaluation Project Group. RESULTS: We describe how to estimate the cost of preventing (or achieving) an event to inform assessments of cost-effectiveness of alternative treatments, when there are no published economic evaluations. Evidence profiles and Summary of Findings tables based on systematic reviews of cost-effectiveness analyses can be created to provide top-level summaries of results and quality of multiple published economic evaluations. We also describe how this information could be integrated in GRADE's EtD frameworks to inform health-related recommendations. Three scenarios representing various levels of available cost-effectiveness evidence were used to illustrate the integration process. CONCLUSION: This GRADE guidance provides practical information for presenting cost-effectiveness data and its integration in the development of health-related recommendations, using the EtD frameworks.

The Effects of Lycopene and Tomato Consumption on Cardiovascular Risk Factors in Adults: A Grade Assessment Systematic Review and Meta-analysis.

BACKGROUND: In recent times, modifying dietary habits to control cardiovascular risk factors has gained significant attention. However, previous studies have yielded inconsistent results regarding the effects of lycopene and tomato consumption on cardiovascular risk factors. OBJECTIVE: The objective of this study was to assess the impact of consuming lycopene and tomatoes on various cardiovascular risks factors such as lipid profile, glycemic control markers, blood pressure, inflammation, oxidative stress, and body weight. METHODS: A systematic literature search was carried out using electronic databases, including PubMed, Web of Science, and Scopus, up to November 2022 to identify eligible Randomized Control Trials (RCTs) evaluating the effect of lycopene and tomato consumption on cardiovascular risk factors. Heterogeneity tests of the selected trials were performed using the I2 statistic. Random effects models were assessed based on the heterogeneity tests, and pooled data were determined as the weighted mean difference (WMD) with a 95% confidence interval (CI). RESULTS: Out of 27,438 records initially identified, a total of 34 studies met the eligibility criteria and were included in this meta-analysis. The results showed that lycopene consumption was associated with a significant reduction in malondialdehyde (MDA) levels, indicating a potential benefit in reducing oxidative stress. However, lycopene and tomato consumption did not have significant effects on other cardiovascular risk factors such as triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), fasting blood glucose (FBG), systolic blood pressure (SBP), diastolic blood pressure (DBP), Intercellular Adhesion Molecule 1 (ICAM-1), c-reactive protein (CRP), interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), body weight, and body mass index (BMI). CONCLUSION: Overall, the findings showed that lycopene and tomato consumption did not affect cardiovascular risk factors. However, lycopene supplementation may result in a significant improvement in MDA levels. With the view to confirming these results, further studies with long-term duration and different doses are needed.

Meta-analysis and GRADE assessment of randomized controlled trials on the efficacy and safety of bimekizumab in psoriatic arthritis patients.

OBJECTIVE: A persistent immune-mediated inflammatory disorder called psoriatic arthritis affects about 25% of persons with psoriasis. Bimekizumab, a humanized monoclonal IgG1 antibody, is a novel therapeutic approach that inhibits homodimers and heterodimers of IL-17A and IL-17F by binding to comparable locations in these molecules. Bimekizumab was the subject of a meta-analysis to assess its efficacy and safety in psoriatic arthritis patients. METHODS: All randomized clinical trials were looked up on PubMed, Scopus, and Web of Science. The Systematic Review Accelerator tool was used to screen them, and RevMan was used to analyze them. The Mean Difference (MD) and 95% Confidence Interval (CI) were used to examine continuous data, whereas the Risk Ratio (RR) and 95% CI were used to evaluate dichotomous data. RESULTS: A total of 1364 participants from 4 trials were included in this meta-analysis. The number of participants who met the American College of Rheumatology 50 threshold was significantly higher in the bimekizumab group compared to the placebo group [RR = 4.94, 95% CI (3.73, 6.55), p < .00001]. Psoriasis Area and Severity Index 100 was achieved by significantly more people in the bimekizumab group than in the placebo group [RR = 11.45, 95% CI (6.67, 19.67), p < .00001]. There was no significant difference between the bimekizumab group and the placebo group in terms of treatment-emergent adverse events [RR = 1.08, 95% CI (0.97, 1.21), p = .15]. CONCLUSION: In comparison to a placebo, bimekizumab treatment significantly improved joint and skin efficacy outcomes. Also, its safety results were acceptable.

Updated guidance regarding the risk of allergic reactions to COVID-19 vaccines and recommended evaluation and management: A GRADE assessment and international consensus approach.

This guidance updates 2021 GRADE (Grading of Recommendations Assessment, Development and Evaluation) recommendations regarding immediate allergic reactions following coronavirus disease 2019 (COVID-19) vaccines and addresses revaccinating individuals with first-dose allergic reactions and allergy testing to determine revaccination outcomes. Recent meta-analyses assessed the incidence of severe allergic reactions to initial COVID-19 vaccination, risk of mRNA-COVID-19 revaccination after an initial reaction, and diagnostic accuracy of COVID-19 vaccine and vaccine excipient testing in predicting reactions. GRADE methods informed rating the certainty of evidence and strength of recommendations. A modified Delphi panel consisting of experts in allergy, anaphylaxis, vaccinology, infectious diseases, emergency medicine, and primary care from Australia, Canada, Europe, Japan, South Africa, the United Kingdom, and the United States formed the recommendations. We recommend vaccination for persons without COVID-19 vaccine excipient allergy and revaccination after a prior immediate allergic reaction. We suggest against >15-minute postvaccination observation. We recommend against mRNA vaccine or excipient skin testing to predict outcomes. We suggest revaccination of persons with an immediate allergic reaction to the mRNA vaccine or excipients be performed by a person with vaccine allergy expertise in a properly equipped setting. We suggest against premedication, split-dosing, or special precautions because of a comorbid allergic history.

Grading of recommendations assessment, development, and evaluation concept article 5: addressing intransitivity in a network meta-analysis.

OBJECTIVES: This article describes considerations for addressing intransitivity when assessing the certainty of the evidence from network meta-analysis (NMA) using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. Intransitivity is induced by effect modification, that is, when the magnitude of the effect between an intervention and outcome differs depending on the level of another factor. STUDY DESIGN AND SETTING: To develop this GRADE concept paper, the lead authors conducted iterative discussions, computer simulations, and presentations to the GRADE project group and at GRADE working group meetings. The GRADE Working Group formally approved the article in July 2022. RESULTS: NMA authors can have a higher or a lower threshold to rate down the certainty of the evidence due to intransitivity, which depends on the extent of their concerns regarding the trustworthiness of indirect comparisons, and their view of the relative problems with rating down excessively or insufficiently. NMA authors should consider three main factors when addressing intransitivity: the credibility of effect modification, the strength of the effect modification, and the distribution of effect modifiers across the direct comparisons. To avoid double counting limitations of the evidence, authors should consider the relationship between intransitivity and other GRADE domains. CONCLUSION: NMA authors face theoretic and pragmatic challenges and in most situations need to assess intransitivity without the availability of empirical data. Thus, explicitness regarding perspective is crucial.

Adherence to the Mediterranean diet and risk of frailty and pre-frailty in elderly adults: A systematic review and dose-response meta-analysis with GRADE assessment.

BACKGROUND: Several studies have explored the association between Mediterranean diet and frailty, but reported inconsistent results. This systematic review and dose-response meta-analysis summarized the existing evidence on the relationship between Mediterranean diet and risk of frailty and pre-frailty in elderly adults. METHODS: A systematic search on MEDLINE (PubMed), Scopus, Institute for Scientific Information (ISI) Web of Science and Google Scholar was conducted up to January 2023. Study selection and data extraction were performed by two reviewers working in parallel. Epidemiologic studies reporting relative risks (RRs) or odds ratios (ORs) with 95% confidence intervals (CIs) for frailty/pre-frailty in relation to Mediterranean diet (as a priori dietary pattern) were considered. The overall effect size was determined using a random effects model. The body of evidence was assessed by the GRADE approach. RESULTS: A total of 19 studies (12 cohorts and 7 cross-sectionals) were included. In cohort studies (89,608 participants/ 12,866 cases), the highest versus lowest category of Mediterranean diet was inversely associated with frailty (RR: 0.66; 95%CI: 0.55, 0.78; I2:52.4%, PQ-test=0.02). This association was also significant in cross-sectional studies with 1093 cases among 13,581 participants (OR: 0.44; 95%CI: 0.28, 0.70; I2:81.8%, PQ-test<0.001). Moreover, each 2-point increase in Mediterranean diet score was related to decreased risk of frailty in cohort (RR: 0.86; 95%CI: 0.80, 0.93) and cross-sectional (OR: 0.79; 95%CI: 0.65, 0.95) studies. Nonlinear association showed a decreasing slope in curve, sharper at high scores for cohort studies and a steadily reduction for cross-sectional studies. The certainty of the evidence was graded as high in both cohort and cross-sectional studies. Combining 4 effect sizes of 4 studies (12,745 participants/ 4363 cases), the highest adherence to Mediterranean diet was linked to a lower risk of pre-frailty, as well (pooled OR: 0.73; 95%CI: 0.61, 0.86; I2:40.9%, PQ-test=0.17). CONCLUSION: Adherence to Mediterranean diet is inversely associated with risk of frailty and pre-frailty in older adults and thus, has a considerable impact on health of this population.

Clinical efficacy and safety of compound Congrong Yizhi Capsules on Alzheimer's disease in mainland China: A systematic review with trial sequential analysis and GRADE assessment.

ETHNOPHARMACOLOGICAL RELEVANCE: Alzheimer's disease (AD) is a degenerative disease of the central nervous system (CNS) with insidious onset. AD is also the most common cause of dementia. Compound Congrong Yizhi Capsules (CCYC), a traditional Chinese medicine compound developed by the team of Beijing University of Chinese Medicine, has been widely used to treat AD. AIM OF THIS STUDY: To systematically evaluate the clinical efficacy and safety of CCYC for AD by meta-analysis, Trial Sequential Analysis (TSA) and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. METHODS: This study was registered at PROSPERO (CRD42022295496). Randomized controlled trials (RCTs) of CCYC as the treatment for AD published before December 1, 2021 were retrieved from 4 Chinses databases, 4 English databases and 2 clinical trials registration systems. RevMan 5.4 and STATA 17.0 was used to conduct the meta-analysis of the included studies, the quality of outcomes was rated by the GRADE system, the TSA was conducted by TSA 0.9.5.10 software. RESULTS: Seven studies were included, and the total sample size was 746. Meta-analysis showed that 6 months of treatment with CCYC plus conventional western medicine treatments (CTs) improved MMSE scores compared with CTs alone (WMD: 4.32, 95% CI: 3.23, 5.42), and TSA confirmed that more trials in the future will not reverse the result. Among which, CCYC combined with donepezil can significantly improve MMSE scores (WMD: 3.54, 95% CI: 2.86, 4.22). CCYC combined with olanzapine also showed good effect on both MMSE (WMD: 6.49, 95% CI: 5.54, 7.44) and ADL scores (WMD: 5.23, 95% CI: 4.63, 5.83). No serious adverse events were reported. The strengths of the evidences above are MODERATE. CONCLUSION: CCYC combined with cognition-modifying western medicine can improve cognitive function, mental behavioural symptoms, and activities of daily living in AD patients with good safety.

The association between circulating 25-hydroxyvitamin D levels and preeclampsia: a systematic review and dose-response meta-analysis of epidemiologic studies with GRADE assessment.

CONTEXT: Although some studies have examined the connection between circulating 25-hydroxyvitamin D (25(OH)D) concentrations and preeclampsia (PE) risk, the results were inconsistent. OBJECTIVE: A dose-response meta-analysis on epidemiologic investigations was conducted to evaluate the relation of 25(OH)D concentration and PE. DATA SOURCE: Electronic databases, including Scopus, MEDLINE (PubMed), the Institute for Scientific Information, Embase, and Google Scholar, were comprehensively search until July 2021. DATA EXTRACTION: A total of 65 observational studies evaluating the link between circulating 25(OH)D concentrations and PE were included. The body of evidence was assessed by the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach. DATA ANALYSIS: Combining 32 effect sizes from 32 prospective studies with 76 394 participants revealed that highest vs lowest circulating 25(OH)D concentrations was significantly related to a 33% reduced risk of PE (relative risk [RR], 0.67; 95%CI, 0.54-0.83). Subgroup analysis by study design revealed that PE risk has significantly decreased in cohort and case-cohort studies (RR, 0.72; 95%CI, 0.61-0.85), and a slight decline was found in nested case-control studies (RR, 0.62; 95%CI, 0.38-1.02). Dose-response analysis in 27 prospective studies with 73 626 participants illustrated that each 10 ng/mL increment in circulating 25(OH)D concentration led to a 14% reduced incidence of PE (RR, 0.86; 95%CI, 0.83-0.90). A U-shaped significant association in nonlinear dose-response analysis was found between 25(OH)D and PE. A significant inverse association was also found between highest vs lowest circulating 25(OH)D concentration and PE in 32 nonprospective studies with 37 477 participants (odd ratio, 0.37; 95%CI, 0.27-0.52). This inverse association was significant in almost all subgroups, based on different covariates. CONCLUSION: This meta-analysis of observational investigations showed blood 25(OH)D levels were negatively related to PE risk, in a dose-response manner. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. CRD42021267486.

Bracing and taping interventions for individuals with vertebral fragility fractures: a systematic review of randomized controlled trials with GRADE assessment.

This systematic review analyzes the effects of bracing and taping after osteoporotic vertebral fractures. Spinal orthose may have positive effects on pain, but the evidence is of very low certainty. Clinical judgment is recommended when prescribing spinal orthoses. PURPOSE: To examine the effects of bracing and taping interventions on pain, physical functioning, health-related quality of life, back extensor strength, kyphosis curvature, and adverse events in individuals with vertebral fragility fractures. METHODS: Four databases were searched from inception up to January 2022. We included randomized controlled trials testing the effect of bracing or taping interventions compared with a non-intervention control in adults ≥ 45 years with vertebral fragility fractures. Narrative syntheses were presented for all the outcomes. We assessed the risk of bias using the Cochrane Risk of Bias Assessment Tool and the certainty of evidence using the Grading of Recommendations Assessment, Development and Evaluation. RESULTS: Three studies were included. Soft bracing interventions exhibited inconsistent effects on pain. One study showed no difference between groups, and another study should a decrease in pain in the soft bracing group compared to the control group. Rigid bracing interventions did not have a significant change in pain between the control and intervention groups. One study demonstrated a decrease in pain at rest (VAS: - 10.8 ± 19.3) and during movement (VAS: - 20.9 ± 29.8) after a taping intervention. The other outcomes were not consistent across studies. CONCLUSIONS: Spinal orthoses may improve pain in people with vertebral fractures; however, we cannot draw definitive conclusions on the efficacy or harms of bracing or taping due to the very low certainty evidence and the small number of studies. Effects on other outcomes are uncertain.

Parches transdérmicos anticonceptivos: evaluación de tecnología sanitaria / Contraceptive transdermal patches: health technology assessment

INTRODUCCIÓN: La anticoncepción es un derecho, y es obligación del Estado garantizar el acceso a métodos anticonceptivos efectivos, seguros y de calidad. Se realizó una evaluación de tecnología sanitaria sobre los parches anticonceptivos transdérmicos. MÉTODOS: Un equipo multidisciplinario e independiente designado por el Comité Provincial de Biotecnologías de Neuquén buscó información epidemiológica, regulatoria y evidencias científicas sobre eficacia, seguridad y adherencia. Se analizó y sistematizó siguiendo metodología GRADE (Grading of Recommendations Assessment, Development and Evaluation) y CASPe (Critical Appraisal Skills Programme Español). RESULTADOS: El único parche autorizado en Argentina para su comercialización libera 33,9 µg/día de etinilestradiol y 203 µg/día de norelgestromina. Su prospecto en Argentina, EE.UU. y Europa lo asocia al doble de riesgo de enfermedad tromboembólica venosa si se compara con las píldoras anticonceptivas que provee el Estado. Esto coincide con resultados de estudios de cohortes de alta calidad. Los parches proveen similar eficacia anticonceptiva a corto plazo, pero con altas tasas de abandono en el seguimiento. La Organización Mundial de la Salud no los ha incluido en su listado de medicamentos esenciales. Los parches son más costosos que otros métodos disponibles. DISCUSIÓN: Sobre la base de los principios de beneficencia, no maleficencia, de precaución y de proporcionalidad, no se recomienda la incorporación de parches.(AU)

INTRODUCTION: Contraception is a right, being an obligation of the State to guarantee access to effective, safe and quality contraceptive methods. A health technology assessment was carried out on transdermal contraceptive patches. METHODS: A multidisciplinary and independent team appointed by the Provincial Biotechnology Committee of Neuquén searched for epidemiological and regulatory information and scientific evidence on efficacy, safety and adherence. It was analyzed and systematized following the GRADE (Grading of Recommendations Assessment, Development and Evaluation) and CASPe (Critical Appraisal Skills Programme Español) methodology. RESULTS: The only patch authorized for commercialization in Argentina releases 33.9 µg/day of ethinylestradiol and 203 µg/day of norelgestromin. Its package insert in Argentina, the US and Europe highlights that the risk of venous thromboembolic disease is twice as high compared to the contraceptive pills provided by the State. This is consistent with results from high-quality cohort studies. Patches provide similar short-term contraceptive efficacy, but with high dropout rates at follow-up. The World Health Organization has not included them in its list of essential medicines. Patches are more expensive than other available methods. DISCUSSION: Based on the principles of beneficence, non-maleficence, precaution and proportionality, the incorporation of patches is not recommended.(AU)

The impact of climate change on health needs structured evidence assessment and an evidence to action framework to make decisions: a proposal to adopt the GRADE approach.

OBJECTIVES: To highlight how using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach to understand the certainty in the evidence about the impact of climate change in health outcomes increases transparency. Also, how GRADE can enhance communication and decisions about adaptation and mitigation strategies. STUDY DESIGN AND SETTING: We developed a narrative review based on an assessment of exiting systematic reviews addressing the effect of climate change on health outcomes and the impact of mitigation and adaptation strategies. RESULTS: Adopting structured approaches such as GRADE to tackle the impact of climate change on health may help to (1) define the specific question to be addressed; (2) summarize the evidence in a structured way and assess uncertainty; (3) provide a systematic framework to move from evidence to action and to offer recommendations of different strength; (4) provide a systematic way to adapt recommendations to specific settings; and (5) provide a framework to assess the certainty of modeled evidence. CONCLUSION: In this article, we describe epidemiologic principles that could be used to move decision-making in climate change forward.

Management of REM sleep behavior disorder: an American Academy of Sleep Medicine systematic review, meta-analysis, and GRADE assessment.

This systematic review provides supporting evidence for a clinical practice guideline for the management of rapid eye movement (REM) sleep behavior disorder in adults and children. The American Academy of Sleep Medicine commissioned a task force of 7 experts in sleep medicine. A systematic review was conducted to identify randomized controlled trials and observational studies that addressed interventions for the management of REM sleep behavior disorder in adults and children. Statistical analyses were performed to determine the clinical significance of critical and important outcomes. Finally, the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) process was used to assess the evidence for making recommendations. The literature search identified 4,690 studies; 148 studies provided data suitable for statistical analyses; evidence for 45 interventions is presented. The task force provided a detailed summary of the evidence assessing the certainty of evidence, the balance of benefits and harms, patient values and preferences, and resource use considerations. CITATION: Howell M, Avidan AY, Foldvary-Schaefer N, et al. Management of REM sleep behavior disorder: an American Academy of Sleep Medicine systematic review, meta-analysis, and GRADE assessment. J Clin Sleep Med. 2023;19(4):769-810.

EAES rapid guideline: updated systematic review, network meta-analysis, CINeMA and GRADE assessment, and evidence-informed European recommendations on the management of common bile duct stones.

BACKGROUND: Choledocholithiasis presents in a considerable proportion of patients with gallbladder disease. There are several management options, including preoperative or intraoperative endoscopic cholangiopancreatography (ERCP), and laparoscopic common bile duct exploration (LCBDE). OBJECTIVE: To develop evidence-informed, interdisciplinary, European recommendations on the management of common bile duct stones in the context of intact gallbladder with a clinical decision to intervene to both the gallbladder and the common bile duct stones. METHODS: We updated a systematic review and network meta-analysis of LCBDE, preoperative, intraoperative, and postoperative ERCP. We formed evidence summaries using the GRADE and the CINeMA methodology, and a panel of general surgeons, gastroenterologists, and a patient representative contributed to the development of a GRADE evidence-to-decision framework to select among multiple interventions. RESULTS: The panel reached unanimous consensus on the first Delphi round. We suggest LCBDE over preoperative, intraoperative, or postoperative ERCP, when surgical experience and expertise are available; intraoperative ERCP over LCBDE, preoperative or postoperative ERCP, when this is logistically feasible in a given healthcare setting; and preoperative ERCP over LCBDE or postoperative ERCP, when intraoperative ERCP is not feasible and there is insufficient experience or expertise with LCBDE (weak recommendation). The evidence summaries and decision aids are available on the platform MAGICapp ( https://app.magicapp.org/#/guideline/nJ5zyL ). CONCLUSION: We developed a rapid guideline on the management of common bile duct stones in line with latest methodological standards. It can be used by healthcare professionals and other stakeholders to inform clinical and policy decisions. GUIDELINE REGISTRATION NUMBER: IPGRP-2022CN170.

UEG and EAES rapid guideline: Update systematic review, network meta-analysis, CINeMA and GRADE assessment, and evidence-informed European recommendations on surgical management of GERD.

BACKGROUND: There are several options for the surgical management of GERD in adults. Previous guidelines and systematic reviews have compared the effects of total fundoplication versus pooled effects of different techniques of partial fundoplication. OBJECTIVE: To develop evidence-informed, trustworthy, pertinent recommendations on the use of total, posterior partial and anterior partial fundoplications for the management of GERD in adults. METHODS: We performed an update systematic review, network meta-analysis, and evidence appraisal using the GRADE and the Confidence in Network Meta-Analysis methodologies. An international, multidisciplinary panel of surgeons, gastroenterologists, and a patient representative reached unanimous consensus through an evidence-to-decision framework to select among multiple interventions, and a Delphi process to formulate the recommendation. The project was developed in an online authoring and publication platform (MAGICapp), and was overseen by an external auditor. RESULTS: We suggest posterior partial fundoplication over total posterior or anterior 90° fundoplication in adult patients with GERD. We suggest anterior >90° fundoplication as an alternative, although relevant comparative evidence is limited (weak recommendation). The guideline, with recommendations, evidence summaries and decision aids in user friendly formats can also be accessed in MAGICapp: https://app.magicapp.org/#/guideline/j20X4n. CONCLUSION: This rapid guideline was developed in line with highest methodological standards and provides evidence-informed recommendations on the surgical management of GERD. It provides user-friendly decision aids to inform healthcare professionals' and patients' decision making.

EAES rapid guideline: systematic review, meta-analysis, GRADE assessment, and evidence-informed European recommendations on appendicitis in pregnancy.

BACKGROUND: Clinical practice recommendations for the management of acute appendicitis in pregnancy are lacking. OBJECTIVE: To develop an evidence-informed, trustworthy guideline on the management of appendicitis in pregnancy. We aimed to address the questions of conservative or surgical management, and laparoscopic or open surgery for acute appendicitis. METHODS: We performed a systematic review, meta-analysis, and evidence appraisal using the GRADE methodology. A European, multidisciplinary panel of surgeons, obstetricians/gynecologists, a midwife, and 3 patient representatives reached consensus through an evidence-to-decision framework and a Delphi process to formulate the recommendations. The project was developed in an online authoring and publication platform (MAGICapp). RESULTS: Research evidence was of very low certainty. We recommend operative treatment over conservative management in pregnant patients with complicated appendicitis or appendicolith on imaging studies (strong recommendation). We suggest operative treatment over conservative management in pregnant patients with uncomplicated appendicitis and no appendicolith on imaging studies (weak recommendation). We suggest laparoscopic appendectomy in patients with acute appendicitis until the 20th week of gestation, or when the fundus of the uterus is below the level of the umbilicus; and laparoscopic or open appendectomy in patients with acute appendicitis beyond the 20th week of gestation, or when the fundus of the uterus is above the level of the umbilicus, depending on the preference and expertise of the surgeon. CONCLUSION: Through a structured, evidence-informed approach, an interdisciplinary panel provides a strong recommendation to perform appendectomy for complicated appendicitis or appendicolith, and laparoscopic or open appendectomy beyond the 20th week, based on the surgeon's preference and expertise. GUIDELINE REGISTRATION NUMBER: IPGRP-2022CN210.