P050 Consensus based practice guidelines for the management and treatment of Juvenile familial Mediterranean fever: the Egyptian College of Paediatric Rheumatology initiative

Background Familial Mediterranean fever (FMF) is the most common monogenic auto-inflammatory disease, with the highest prevalence amongst Mediterranean countries including Egypt (where there is high carrier rate of MEFV gene), characterized by recurrent attacks of fever and polyserositis. Mutations in the MEFV gene encoding pyrin has been associated with the disease, which causes exaggeration of the inflammatory response through uncontrolled interleukin production. Issuing updated treatment recommendations are vital for the treating healthcare professionals to get well acquainted with its diagnosis & treatment. To produce consensus-based recommendations to guide the early diagnosis, management and follow-up of patients with FMF. Methods The Patient/Population, Intervention, Comparison, and Outcomes (PICO) questions were developed and refined by the core team. A qualitative synthesis of scientific evidence based on systematic review and clinical experience was conducted to compile evidence for the diagnosis and management of FMF. A consensus process was conducted among the expert panel to generate the final recommendations and grade their strength. 3 rounds of Delphi process were carried out. Results Following 3 Delphi rounds, recommendations were developed for: early diagnosis, who to treat, treatment targets, genetic testing and its interpretation in association with clinical presentation, treatment of FMF and dealing with acute attacks, monitoring of management, identify treatment response, systemic affection, persistent attacks or inflammation, resistant cases, protracted symptoms, as well as remission status. Algorithm for patients’ diagnosis and management is provided. The final document comprises 12 recommendations, each presented with its degree of agreement (0–10), Level of agreement, grade of recommendation and rationale. The degree of agreement was >7/10 in all instances. Conclusion This guideline provides comprehensive approach to the accurate diagnosis and effective management/monitoring of FMF. It also represents a model for the incorporation of medical genetics practice into the more traditional domains of general medicine.

Processed Electroencephalogram-Based Monitoring to Guide Sedation in Critically Ill Patients: A Systematic Review and International Expert Panel-Based Consensus Recommendations

BackgroundThe literature related to the use of processed EEG (pEEG) for depth of sedation (DOS) monitoring is increasing, however it is unclear how to use this type of monitoring for critical care patients within the intensive care unit (ICU).MethodsWe performed a systematic review of the literature according to the Grade of Recommendation assessment, Development, and Evaluation (GRADE) approach. The modified Delphi method was utilised by a team of experts to produce statements and recommendations derived from study questions. Three separate online rounds discussing 89 statements categorized into four domains were formulated. The panelists rated the appropriateness of each statement and were able to suggest modifications or addition of statements. An analysis of anonymised ratings of the statements by part of the panel followed each Delphi round and previously validated criteria were used to define appropriateness and consensus.ResultsLevel of evidence regarding the four domains was very low. Fourteen panelists participated in the Delphi rounds and consensus was reached for 28 out of 89 statements, from which the reccomendations were created. The main findings were that DOS monitoring should be performed in critically ill patients whenever clinical evaluation is not possible, it should be performed by continuous pEEG techniques and the resulting data depicted with graphical tools to facilitate detection of excessive sedation, a potential cause of burst-suppression, and finally, structured training is suggested to achieve a basic pEEG competency.ConclusionsAlthough evidence on using DOS monitors in ICU is scarce and further research is required in order to better define the benefits of using pEEG, the results of this consensus highlight the general agreement that critically-ill patients would benefit from this type of neuromonitoring.

Laparoscopy in Emergency: Why Not? Advantages of Laparoscopy in Major Emergency: A Review

A laparoscopic approach is suggested with the highest grade of recommendation for acute cholecystitis, perforated gastroduodenal ulcers, acute appendicitis, gynaecological disorders, and non-specific abdominal pain (NSAP). To date, the main qualities of laparoscopy for these acute surgical scenarios are clearly stated: quicker surgery, faster recovery and shorter hospital stay. For the remaining surgical emergencies, as well as for abdominal trauma, the role of laparoscopy is still a matter of debate. Patients might benefit from a laparoscopic approach only if performed by experienced teams and surgeons which guarantee a high standard of care. More precisely, laparoscopy can limit damage to the tissue and could be effective for the reduction of the overall amount of cell debris, which is a result of the intensity with which the immune system reacts to the injury and the following symptomatology. In fact, these fragments act as damage-associated molecular patterns (DAMPs). DAMPs, as well as pathogen associated molecular patterns (PAMPs), are recognised by both surface and intracellular receptors of the immune cells and activate the cascade which, in critically ill surgical patients, is responsible for a deranged response. This may result in the development of progressive and multiple organ dysfunctions, manifesting with acute respiratory distress syndrome (ARDS), coagulopathy, liver dysfunction and renal failure. In conclusion, none of the emergency surgical scenarios preclude laparoscopy, provided that the surgical tactic could ensure sufficient cleaning of the abdomen in addition to resolving the initial tissue damage caused by the “trauma”.

Management of particular clinical situations in psoriatic arthritis: an expert’s recommendation document based on systematic literature review and extended Delphi process

To establish practical recommendations for the management of patients with psoriatic arthritis (PsA) with particular clinical situations that might lead to doubts in the pharmacological decision-making. A group of six expert rheumatologists on PsA identified particular clinical situations in PsA. Then, a systematic literature review (SLR) was performed to analyse the efficacy and safety of csDMARDs, b/tsDMARDs in PsA. In a nominal group meeting, the results of the SLR were discussed and a set of recommendations were proposed for a Delphi process. A total of 65 rheumatologists were invited to participate in the Delphi. Agreement was defined if ≥ 70% of the participants voted ≥ 7 (from 1, totally disagree to 10, totally agree). For each recommendation, the level of evidence and grade of recommendation was established based on the Oxford Evidence-Based Medicine categorisation. Particular clinical situations included monoarthritis, axial disease, or non-musculoskeletal manifestations. The SLR finally comprised 131 articles. A total of 16 recommendations were generated, all but 1 reached consensus. According to them, it is crucial to carefully analyse the impact of individual manifestations on patients (disability, quality of life, etc.), but also to recognise the impact of each drug singularities on selected clinical phenotypes to adopt the most appropriate treatment strategy. Early diagnosis and treatment to target approach, along with a close risk management, is also necessary. These recommendations are intended to complement gaps in national and international guidelines by helping health professionals address and manage particular clinical situations in PsA.

Development of rapid advice guideline and standard and continuous updating guideline: experiences and practice

We published rapid advice guidelines and updated guidelines for coronavirus disease 2019 (COVID-19) management on February 6, 2020, and September 4, 2020, respectively. These two guidelines vary widely in their developmental background, type of evidence, grade of recommendation and so on. We shared our experience for the development of these two guidelines to help clinical practitioners better understand and implement guidelines and to help guideline developers facilitate communication and discussion for guideline development during the pandemic.

Evaluation of root resorption following orthodontic intrusion: a systematic review and meta-analysis

Summary Background/Objective To quantify the expected amount of orthodontically induced root resorption (OIRR) after orthodontic intrusion and assess the treatment-related factors. Search methods and eligibility criteria Six electronic databases and partial grey literature were searched without limitations regarding language or publication year until April 2020. Randomized clinical trials and non-randomized prospective and retrospective studies evaluating root resorption after orthodontic intrusion were included. Data collection and analysis Risk of bias (RoB) assessment was performed with the Cochrane Collaboration’s RoB Tool 2.0 and ROBINS-I tool for the randomized and non-randomized studies, respectively. The data were combined into two random-effects meta-analyses estimating OIRR following orthodontic intrusion. One evaluated OIRR in the anterior region, while the other assessed OIRR in the posterior region. Sub-group analyses regarding the type of mechanics applied, duration of intrusion, amount of force, and sensitivity analysis of the study design and imaging examinations were also performed. The certainty of the evidence was assessed through the Grade of Recommendation, Assessment, Development, and Evaluation (GRADE) approach. Results The qualitative analysis included 14 studies; however, the meta-analysis was performed with 7 records. The random-effects model assumes that 0.72 mm [95% confidence interval (CI): 0.16 to 1.28] and 0.41 mm (95% CI: −0.24 to 1.07) of OIRR should be expected in the incisors and the molars, respectively. Sub-group analyses showed that the assessed treatment-related factors presented minimum impact in OIRR after orthodontic intrusion. The GRADE resulted in moderate and low certainty regarding the meta-analysis. Limitations The major limitation of the present meta-analysis is that OIRR can be affected by several factors, some of which are assessed in this review. Conclusions Orthodontic intrusion, evaluated as an isolated mechanic, caused less than 1 mm of OIRR, which is within the acceptable limits for clinical implication. Treatment-related factors did not show a significant influence on OIRR. Registration This review was registered in PROSPERO, protocol number CRD42018098495.

Prise en charge de l’exacerbation sévère d’asthme

Contexte : La Société Française de Médecine d’Urgence, la Société de Réanimation de Langue Française et le GroupeFrancophone de Réanimation et d’Urgences Pédiatriques ont émis des recommandations sur la prise en charge del’exacerbation sévère d’asthme (ESA) chez l’enfant et l’adulte.Résultats : Les recommandations ont concerné 5 champs : diagnostic, traitement pharmacologique, modalités d’oxygénothérapie et de ventilation, orientation du patient, spécifi cités de la femme enceinte. L’analyse de la littérature et laformulation des recommandations ont été conduites selon la méthode GRADE (Grade of Recommendation Assessment,Development and Evaluation). Une recherche bibliographique portant sur les publications indexées dans les bases dedonnées PubMed™ et Cochrane™ a été réalisée.Sur les 21 recommandations formalisées obtenues, 4 avaient un niveau de preuve élevé (GRADE 1+/-) et 7 un niveaude preuve faible (GRADE 2 +/-). Pour 10 recommandations, la méthode GRADE n’a pas pu être appliquée, résultanten un avis d’experts. Un accord fort a été obtenu pour toutes les recommandations.Conclusion : Le travail conjoint de 36 experts issus de 3 sociétés savantes a permis d’obtenir 21 recommandations formalisées pour aider à la prise en charge aux urgences et en soins intensifs des patients adultes et pédiatriques avec une ESA.

Australian clinical consensus guideline for the subacute rehabilitation of childhood stroke

Childhood stroke results in long-term, multifaceted difficulties, affecting motor, cognitive, communication, and behavioral domains of function which impact on participation and quality of life. The Childhood Stroke Consensus Rehabilitation Guideline was developed to improve the care of children with stroke by providing health professionals with recommendations to assist in their rehabilitative treatment. Clinical questions were formulated to inform systematic database searches from 2001 to 2016, limited to English and pediatric studies. SIGN methodology and the National Health and Medical Research Council system were used to screen and classify the evidence. The Grade of Recommendation, Assessment, Development and Evaluation system was used to grade evidence as strong or weak. Where evidence was inadequate or absent, a modified Delphi consensus process was used to develop consensus-based recommendations. The guideline provides 56 recommendations (1 evidence-based recommendation and 55 consensus recommendations). These relate to the framework of rehabilitation service delivery as well as domain-specific rehabilitation treatment strategies for each domain of function. It is anticipated that this guideline will provide health professions with recommendations to improve the subacute care of children with stroke both in Australia and internationally.

Role of N-Acetylcysteine in the Treatment of Acute Nonacetaminophen, Nonalcoholic and Nonviral Hepatitis: A Meta-analysis

Introduction N-acetylcysteine (NAC) has been extensively investigated for the use in acetaminophen and alcoholic hepatitis and is indicated in acetaminophen overdose. Studies assessing the effect of NAC on other forms of acute hepatitis in adult patients are limited and therefore here we aimed at evaluating the effect of NAC on survival in nonacetaminophen, nonalcoholic and nonviral hepatitis in adults. Methods A comprehensive literature search up to September 2019 was completed for randomized controlled trials (RCTs) comparing NAC to placebo in the management of acute nonacetaminophen, nonalcoholic and nonviral hepatitis. Studies with insufficient data, non-RCT or nonprospective design, paediatric studies and studies with no comparator were excluded. Study selection, quality assessment and data extraction were independently performed by two co-authors. Primary outcome was survival. Secondary outcomes were an increase in infection rate. We used random model Mantel–Haenszel meta-analysis with Cochrane risk of bias to assess the quality of included studies. The recommendation was presented using the GRADE framework. Results Seven out of 42 retrieved studies were included. Study population included patients with post-liver transplant, postsurgical, hypoxia-induced, ischemic and other nonalcoholic hepatitis. There was no difference in overall survival between NAC and placebo (odds ratio [OR] 0.95 [0.55 to 1.62]) in seven studies including 1033 patients. Furthermore, there was no difference in the rate of infection between NAC and placebo (OR 0.87 [0.43 to 1.79]). Random model analysis was used to adjust the effect of statistically significant heterogeneity in both analyses (P = 0.02). Lack of blinding in one study was found as a possible source of heterogeneity. Conclusions NAC does not improve overall survival or the rate of infection in patients with acute nonacetaminophen, nonalcoholic and nonviral hepatitis as compared to placebo and should not be recommended in such setting which may even delay a transplant evaluation (level of evidence: 2a, GRADE of recommendation: B).

FRI0071 ANALYSIS OF DATA GAPS IN RHEUMATOID ARTHRITIS

Background:Although ideally Recommendations for the management of rheumatoid arthritis (RA) should be supported by the highest level of evidence, many of which are based on “expert opinion”. This means that there are knowledge gaps to which a part of the research efforts in this disease should be directed.Objectives:1.- Analyze the causes of the low level of evidence in some of the recommendations on diagnosis and management of RA in the main published documents2.- Identify the knowledge gaps that justify said low level of evidence3.- Design actions to respond to the knowledge gaps identified.Methods:Qualitative study. A group of six experts in systematic review of the literature was selected. Fourteen documents of national and international recommendations on RA (EULAR, ACR and SER) of the last 5 years were analyzed by a peer review. They selected recommendations with low level of evidence (Oxford 4 and 5) / grade of recommendation (C and D), and classified by areas (diagnosis, monitoring, treatment, others) and then possible causes of low level of evidence were analyzed. These were submitted to a Delphi to select the 10 recommendations in which participants considered it more critical to obtain quality evidence. Subsequently, actions were proposed to improve the levels of evidence in general and, through the PICOS structure (population, intervention, comparator, study design) specific studies were proposed to respond to the issues raised in these 10 recommendationsResults:185 recommendations were found that had a low level of evidence / grade of recommendation, most related to the treatment of RA. The two most frequent causes of this low level of evidence and / or the degree of recommendation were the absence of studies and an incorrect classification of the level of evidence and / or degree of recommendation. In addition, other reasons and methodological barriers were found for which nine critical recommendations were finally selected for which new PICOs were developed with which to propose targeted research projectsConclusion:It is necessary to improve the methodological approach in the RA recommendations guidelines to correct errors and fill gaps with appropriate studies.Table 1.Actions to increase the level of evidence / recommendation.#Action1Prioritization of research towards knowledge gaps with the design and development of specific studies2Increase knowledge of experts in the methodology of consensus documents (including RSL, formulation of recommendations, etc.)3Supervision of the entire process by expert methodologists, to ensure a correct allocation of the levels of evidence and degree of recommendation4Review and select those topics that are really of interest and should be reviewed and can be answered5Expert opinion should never become a recommendation, but will be included in the text that accompanies that recommendation.6Clear syntax will be used and short recommendations will be made7Establishment and application of homogeneous criteria to formulate recommendationsKey words: Rheumatoid arthritis, recommendations, data gapsDisclosure of Interests:gloria candelas: None declared, Lucía Silva-Fernández: None declared, Maria Montoro Employee of: Pfizer employee, Abad Hernández: None declared, Jose Ramón Maneiro: None declared, Virginia Villaverde: None declared, Loreto Carmona Grant/research support from: Novartis Farmaceutica, SA, Pfizer, S.L.U., Merck Sharp & Dohme España, S.A., Roche Farma, S.A, Sanofi Aventis, AbbVie Spain, S.L.U., and Laboratorios Gebro Pharma, SA (All trhough institution), Estíbaliz Loza Grant/research support from: Roche, Pfizer, Abbvie, MSD, Novartis, Gebro, Adacap, Astellas, BMS, Lylly, Sanofi, Eisai, Leo, Sobi, Susana Gómez Employee of: Pfizer employee, Monica Valderrama Consultant of: Pfizer employee, Ana Ortiz: None declared