Society for Maternal-Fetal Medicine Special Statement: Grading of Recommendations Assessment, Development, and Evaluation (GRADE) update.

The Society for Maternal-Fetal Medicine Publications Committee first adopted the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system in 2013. This document provides an update on the Society for Maternal-Fetal Medicine Publications Committee process for creating evidence-based practice recommendations and describes the GRADE process as it is currently implemented in the SMFM Consult and Guidelines series.

No 369 - Prise en charge de la grossesse aprés une mortinaissance.

OBJECTIF: L'objectif principal de la présente déclaration de consensus est d'élaborer des énoncés de consensus qui guideront la pratique clinique et des recommandations pour les soins prénataux et les soins intrapartum, et les considérations psychosociales dont il faut tenir compte pour prendre soin des femmes enceintes ayant des antécédents de mortinaissance. UTILISATEURS CIBLES: Les cliniciens participant à la prise en charge obstétrique des femmes ayant des antécédents de mortinaissance ou d'autres formes de décès périnatal. POPULATION CIBLE: Les femmes et les familles recevant des soins après une grossesse s'étant soldée par une mortinaissance ou une autre forme de décès périnatal. ÉVIDENCE: La présente directive clinique résume la littérature publiée et énonce un consensus général sur la prise en charge des grossesses suivant une mortinaissance ou un décès périnatal. Nous avons interrogé les bases de données MEDLINE, Embase et Cochrane au moyen des mots-clés : « previous stillbirth ¼, « perinatal loss ¼ et « subsequent pregnancy ¼. Nous avons ensuite étudié les résultats et lu les articles pertinents. Nous avons également consulté les références des articles retenus et les documents citant des études pertinentes. Les données ont ensuite été présentées pendant une réunion de consensus, et les énoncés ont été formulés. En raison du manque de données probantes, nous avons également consulté les cheminements de soins de cliniques spécialisées. VALIDATION: Le contenu et les lignes directrices ont été élaborés par les auteurs principaux en consultation avec les participants à la rencontre. Le Conseil d'administration de la Société des obstétriciens et gynécologues du Canada a approuvé la version finale avant publication. La qualité des données probantes a été évaluée au moyen des critères de l'approche GRADE (Grading of Recommendations Assessment, Development and Evaluation) [tableau 1]. L'interprétation des recommandations solides et conditionnelles est décrite dans le tableau 2. Le résumé des conclusions peut être fourni sur demande. AVANTAGES, INCONVéNIENTS, COûTS: Nous avons exploré une approche multidisciplinaire de prestation des soins prénataux et intrapartum aux femmes et aux familles ayant des antécédents de mortinaissance ou de décès périnatal. Bien qu'il manque de données probantes dans ce domaine, certains membres du groupe de travail fournissent ces soins à des femmes et à des familles dans plusieurs pays et nous ont fait part de leurs connaissances et de leurs expériences dans le but de guider les soins. MIS-à-JOUR: Une revue des données probantes sera menée cinq ans après la publication de la présente directive clinique afin d'évaluer si une mise à jour complète ou partielle s'impose. Cependant, si de nouvelles données probantes importantes sont publiées avant la fin du cycle de cinq ans, le processus pourrait être accéléré afin que certaines recommandations soient mises à jour rapidement. COMMANDITAIRES: La présente directive clinique a été élaborée à l'aide de ressources financées par la Société des obstétriciens et gynécologues du Canada et le Programme pour les femmes et les bébés du Centre Sunnybrook des sciences et la santé tableau 1,2. DéCLARATIONS SOMMAIRES ET RECOMMANDATIONS.

A systematic review and meta-analysis of nut consumption and incident risk of CVD and all-cause mortality.

Dietary patterns containing nuts are associated with a lower risk of CVD mortality, and increased nut consumption has been shown to have beneficial effects on CVD risk factors including serum lipid levels. Recent studies have reported on the relationship between nut intake and CVD outcomes and mortality. Our objective was to systematically review the literature and quantify associations between nut consumption and CVD outcomes and all-cause mortality. Five electronic databases (through July 2015), previous reviews and bibliographies of qualifying articles were searched. In the twenty included prospective cohort studies (n 467 389), nut consumption was significantly associated with a lower risk of all-cause mortality (ten studies; risk ratio (RR) 0·81; 95 % CI 0·77, 0·85 for highest v. lowest quantile of intake, P het=0·04, I 2=43 %), CVD mortality (five studies; RR 0·73; 95 % CI 0·68, 0·78; P het=0·31, I 2=16 %), all CHD (three studies; RR 0·66; 95 % CI 0·48, 0·91; P het=0·0002, I 2=88 %) and CHD mortality (seven studies; RR 0·70; 95 % CI 0·64, 0·76; P het=0·65, I 2=0 %), as well as a statistically non-significant reduction in the risk of non-fatal CHD (three studies; RR 0·71; 95 % CI 0·49, 1·03; P het=0·03, I 2=72 %) and stroke mortality (three studies; RR 0·83; 95 % CI 0·69, 1·00; P het=0·54, I 2=0 %). No evidence of association was found for total stroke (two studies; RR 1·05; 95 % CI 0·69, 1·61; P het=0·04, I 2=77 %). Data on total CVD and sudden cardiac death were available from one cohort study, and they were significantly inversely associated with nut consumption. In conclusion, we found that higher nut consumption is associated with a lower risk of all-cause mortality, total CVD, CVD mortality, total CHD, CHD mortality and sudden cardiac death.

Different doses of dual orexin receptor antagonists in primary insomnia: a Bayesian network analysis.

Background: Systematic comparisons of the doses of the Food and Drug Administration (FDA)-approved dual orexin receptor antagonists (DORAs) for people with insomnia are limited. Methods: PubMed, Embase, Cochrane Library, and Clinicaltrials. gov were systematically searched to identify relevant studies published before 31 October 2022. We assessed the certainty of evidence using the confidence in network meta-analysis (CINeMA) framework. Results: We pooled 7257 participants from 9 randomized controlled trials (RCTs). Moderate to high certainty evidence demonstrated suvorexant (20 and 40 mg) and daridorexant (10 and 50 mg) as the most effective in latency to persistent sleep (LPS) reduction. Lemborexant at 5 and 10 mg was the most effective in subjective sleep onset time (sTSO) reduction. For wake time after sleep onset (WASO), all drugs except daridorexant 5 mg were more effective than placebo. Lemborexant 5 mg was among the best in subjective WASO (sWASO) (moderate to high certainty) and had the highest surface under the curve ranking area (SUCRA) values for sWASO (100%). For total sleep time (TST), suvorexant and daridorexant, except the respective minimum doses, were more effective than placebo, while suvorexant 40 mg and lemborexant 10 mg may have been the most effective for subjective TST (sTST) (low to very low certainty). Suvorexant 40 mg (RR 1.09), suvorexant 80 mg (RR 1.65), and daridorexant 25 mg (RR 1.16) showed a higher safety risk than placebo. Conclusion: Suvorexant 20 mg, lemborexant 5 mg, lemborexant 10 mg, and daridorexant 50 mg represent suitable approaches for insomnia. Clinical Trial Registration: clinicaltrials.gov, PROSPERO (CRD42022362655).

[Re-evaluation of systematic reviews of acupuncture and moxibustion for childhood autism].

OBJECTIVE: To re-evaluate the systematic review/Meta-analysis of acupuncture and moxibustion for childhood autism (CA), aiming to provide decision-making basis for clinical diagnosis and treatment. METHODS: The systematic review and/or Meta-analysis of acupuncture and moxibustion for CA were searched in PubMed, EMbase, Cochrane Library, SinoMed, CNKI and Wanfang databases. The retrieval time was from the database establishment to May 5th, 2022. PRISMA (preferred reporting items for systematic reviews and Meta-analyses) was used to evaluate the report quality, and AMSTAR 2 (a measurement tool to assess systematic reviews 2) was used to evaluate the methodological quality, bubble map was used to construct the evidence map and GRADE was used to evaluate the quality of evidence. RESULTS: A total of 9 systematic reviews were included. The PRISMA scores ranged from 13 to 26. The report quality was low, and there was a serious lack in the aspects of program and registration, search, other analysis and funding. The main problems in methodology included not making prespecified protocol, incomplete retrieval strategy, not providing a list of excluded literatures, and incomplete explanation on heterogeneity analysis and bias risk. The evidence map showed that 6 conclusions were valid, 2 conclusions were possible valid and 1 conclusion was uncertain valid. The overall quality of evidence was low, and the main factors leading to the downgrade were limitations, followed by inconsistency, imprecision and publication bias. CONCLUSION: Acupuncture and moxibustion has a certain effect for CA, but the quality of reporting, methodology and evidence in included literature need to be improved. It is suggested to perform high-quality and standardized research in the future to provide evidence-based basis.

Evidence based recommendations to improve the children oral health in Saudi Arabia.

Aim: Identify the existing evidence base with regards to interventions that address high levels of dental caries. A discussion of the applicability of the evidence to possible replication in Saudi Arabia is presented, alongside recommendations to help reduce dental caries rates in children in Saudi Arabia. Methods: A comprehensive systematic review following PRISMA methods was conducted using three databases: MEDLINE via OVID; EMBASE via OVID and Cochrane Library. Studies were included according to inclusion criteria. AMSTAR2 was used to assess the quality of the included studies, while GRADE was used to assess the quality of evidence. Results: Ten studies were included in this review. The quality of these were 'high' (in two review), moderate (in two studies), low (in one study) and to 'critically low' (5 reviews). The quality of the evidence presented by the reviews ranged from 'moderate' to 'very low'. The interventions methods included MI, one-to-one nutrition advice, educational interventions and dental screening. The applicability of the findings in relation to dental care in Saudi Arabia is discussed and summarized in a narrative. Conclusion: No strong evidence that supported interventions to improve the child oral health in Saudi Arabia was found. None of the included reviews included studies conducted in Saudi Arabia or evaluated interventions among the local community. As for different culture values, norms, beliefs and attitude to those demographics explored in the reviews, it is unclear if interventions with improve oral health among Saudi children. Further research is needed to explore the efficacy of these interventions in a Saudi context.

Impact of organized activities on mental health in children and adolescents: An umbrella review.

Mental health problems are a leading cause of health-related disability among children and adolescents. Organized activities are a possible preventive factor for mental health problems. An aggregated overview of evidence is relevant for youth policymakers and is lacking so far. Thus we aim to provide an overview of published systematic reviews and meta-analyses on the impact of participation in organized sport and non-sport activities (e.g. arts, music) on childhood and adolescent mental health. Systematic reviews were identified through a search in five databases (Embase, MEDLINE, Web of Science core collection, CINAHL and PsycINFO) on 25-March-2021. Systematic reviews about organized activities and mental health outcomes in 0-21-year-olds published in English were included. Two independent reviewers assessed titles, abstracts and full texts, performed data-extraction and quality assessment using the AMSTAR-2 and assessed the quality of evidence. Out of 833 studies, six were considered eligible. Quality of the reviews ranged from critically low to moderate. Most reviews focused on organized sport activities, focusing on: team sport, level of sport involvement, extracurricular and community sport activities. Indications of a positive impact on mental health outcomes were found for participation in team sport, in (school) clubs, and in extracurricular and community sport and non-sport activities. We found a small positive impact of organized sport activities on mental health outcomes among children and adolescents. This seems not to depend on any specific type of organized sport activity. Limited evidence was found for organized non-sport activities.

Continuous positive airway pressure for term and ≥34+0 weeks' gestation newborns at birth: A systematic review.

Background: Respiratory distress is common during transition after birth, but the effect of continuous positive airway pressure applied in the delivery room has not been systematically evaluated in spontaneously breathing term and ≥34+0 weeks' gestation infants.We aimed to compare delivery room continuous positive airway pressure with no delivery room continuous positive airway pressure for term and ≥34+0 weeks' gestation newborn infants at birth. Methods: Information sources: Medline, Embase, Cochrane Databases, Database of Abstracts of Reviews of Effects, and Cumulative Index to Nursing and Allied Health Literature. The Databases were last searched in October 2021.Eligibility criteria: Randomized, quasi-randomized, interrupted time series, controlled before-after, and cohort studies with English abstracts.Synthesis of results: Two authors independently extracted data, assessed risk of bias, and certainty of evidence. The main outcome was admission to the neonatal intensive care unit (NICU) or higher level of care receiving any positive pressure support. Data were pooled using fixed effects models.Risk of bias: Was assessed using the Cochrane Risk of Bias Tool for randomized trials and the Non-Randomized Studies of Interventions Tool (ROBINS-I) for observational studies. Results: In this meta-analysis, two randomized control trials (323 newborns delivered by cesarean section) showed that delivery room continuous positive airway pressure decreased the likelihood of NICU admission (risk ratio (RR) 95% confidence interval (CI) 0.27 (0.11-0.66), p < 0.005) and NICU respiratory support (RR (95% CI) 0.18 (0.05-0.60), p = 0.005) when compared with no delivery room continuous positive airway pressure. However, in two before-after studies (8,476 newborns), delivery room continuous positive airway pressure use was associated with an increased risk of air leak syndrome when compared with no delivery room continuous positive airway pressure. Discussion: Certainty of evidence was very low for all outcomes. Among term and ≥34+0 weeks' gestation infants having or at risk of having respiratory distress, there is insufficient evidence to suggest for or against routine use of continuous positive airway pressure in the delivery room.Funding: No Funding has been received to conduct this study.Clinical Trial Registration: This systematic review has been registered with the International Prospective Register of Systematic Reviews (http://www.crd.york.ac.uk/prospero/) [identifier: CRD42021225812].

Pharmacotherapeutic Impact on Nonalcoholic Steatohepatitis Histology: A Systematic Review and Network Meta-analysis.

Background: Due to lack of targeted treatment options and inconsistent utilization of histologic endpoints among clinical trials, identifying efficacious pharmacotherapies for nonalcoholic steatohepatitis [NASH] has proven challenging. Methods: A thorough systematic review and frequentist random-effects network meta-analysis was performed across all randomized clinical trials reporting a pharmacotherapeutic intervention on biopsy-proven NASH. Primary outcomes were based on the most current, up-to-date recommended histologic endpoints. Results: A total of 40 RCTs were identified including 6593 total patients. The most effective and statistically significant treatment interventions for minimum two-point improvement in NAFLD Activity Score were aldafermin 1 mg [RR 7.69, 95% CI 2.00; 29.57], vitamin E 800 IU in combination with pioglitazone 45 mg [RR 3.38, 95% CI 1.88; 6.07], pioglitazone 45 mg [RR 3.29, 95% CI 1.74; 6.22], vitamin E 800 IU [RR 2.06, 95% CI 1.33; 3.18], resmetirom 80 mg [RR 1.74, 95% CI 1.03; 2.94], obeticholic acid 25 mg [RR 1.63, 95% CI 1.32; 2.01], and obeticholic acid 10 mg [RR 1.31, 95% CI 1.02; 1.67]). The most robust pharmacotherapies for NASH resolution without worsening fibrosis were found to be aldafermin 1 mg [RR 5.77, 95% CI 1.48; 22.51], pioglitazone 45 mg [RR 2.65, 95% CI 1.43; 4.91], vitamin E 800 IU in combination with pioglitazone 45 mg [RR 2.64, 95% CI 1.36; 5.12], pioglitazone 30 mg [RR 2.46, 95% CI 1.56; 3.88], vitamin E 800 IU [RR 1.90, 95% CI 1.20; 3.00], and obeticholic acid 25 mg [RR 1.52, 95% CI 1.03; 2.23]). Obeticholic acid had a significant improvement on fibrosis. Multiple interventions were found to improve individual histologic scores across secondary outcome analyses and are detailed below. Conclusion: This novel systematic review and network meta-analysis represents the most comprehensive investigation to date regarding the pharmacotherapeutic options for biopsy-proven NASH using current recommended histologic endpoints.

Suctioning of clear amniotic fluid at birth: A systematic review.

Context: Upper airway suctioning at birth was considered standard procedure and is still commonly practiced. Negative effects could exceed benefits of suction. Question: In infants born through clear amniotic fluid (P) does suctioning of the mouth and nose (I) vs no suctioning (C) improve outcomes (O). Data sources: Information specialist conducted literature search (12th September 2021, re-run 17th June 2022) using Medline, Embase, Cochrane Databases, Database of Abstracts of Reviews of Effects, and CINAHL. RCTs, non-RCTs and observational studies with a defined selection strategy were included. Unpublished studies, reviews, editorials, animal and manikin studies were excluded. Data extraction: Two authors independently extracted data, risk of bias was assessed using the Cochrane ROB2 and ROBINS-I tools. Certainty of evidence was assed using the GRADE framework. Review Manager was used to analyse data and GRADEPro to develop summary of evidence tables. Meta-analyses were performed if ≥2 RCTs were available. Outcomes: Primary: assisted ventilation. Secondary: advanced resuscitation, oxygen supplementation, adverse effects of suctioning, unanticipated NICU admission. Results: Nine RCTs (n = 1096) and 2 observational studies (n = 418) were identified. Two RCTs (n = 280) with data concerns were excluded post-hoc. Meta-analysis of 3 RCTs, (n = 702) showed no difference in primary outcome. Two RCTs (n = 200) and 2 prospective observational studies (n = 418) found lower oxygen saturations in first 10 minutes of life with suctioning. Two RCTs (n = 200) showed suctioned newborns took longer to achieve target saturations. Limitations: Certainty of evidence was low or very low for all outcomes. Most studies selected healthy newborns limiting generalisability and insufficient data was available for planned subgroup analyses. Conclusions: Despite low certainty evidence, this review suggests no clinical benefit from suctioning clear amniotic fluid from infants following birth, with some evidence suggesting a resulting desaturation. These finding support current guideline recommendations that this practice is not used as a routine step in birth. Funding: The International Liaison Committee on Resuscitation provided access to software platforms, an information specialist and teleconferencing. Clinical Trial Registration: This systematic review was registered with the Prospective Register of Systematic Reviews (https://www.crd.york.ac.uk/prospero/) (identifier: CRD42021286258).

Risk factors for impaired pulmonary diffusion function in convalescent COVID-19 patients: A systematic review and meta-analysis.

Background: The long-term prognosis of COVID-19 survivors remains poorly understood. It is evidenced that the lung is the main damaged organ in COVID-19 survivors, most notably in impairment of pulmonary diffusion function. Hence, we conducted a meta-analysis of the potential risk factors for impaired diffusing capacity for carbon monoxide (DLCO) in convalescent COVID-19 patients. Methods: We performed a systematic search of PubMed, Web of Science, Embase, and Ovid databases for relevant studies from inception until January 7, 2022, limited to papers involving human subjects. Studies were reviewed for methodological quality. Fix-effects and random-effects models were used to pool results. Heterogeneity was assessed using I2. The publication bias was assessed using the Egger's test. PROSPERO registration: CRD42021265377. Findings: A total of eighteen qualified articles were identified and included in the systematic review, and twelve studies were included in the meta-analysis. Our results showed that female (OR: 4.011; 95% CI: 2.928-5.495), altered chest computerized tomography (CT) (OR: 3.002; 95% CI: 1.319-6.835), age (OR: 1.018; 95% CI: 1.007-1.030), higher D-dimer levels (OR: 1.012; 95% CI: 1.001-1.023) and urea nitrogen (OR: 1.004;95% CI: 1.002-1.007) were identified as risk factors for impaired DLCO. Interpretation: Pulmonary diffusion capacity was the most common impaired lung function in recovered patients with COVID-19. Several risk factors, such as female, altered chest CT, older age, higher D-dimer levels and urea nitrogen are associated with impairment of DLCO. Raising awareness and implementing interventions for possible modifiable risk factors may be valuable for pulmonary rehabilitation. Funding: This work was financially supported by Emergency Key Program of Guangzhou Laboratory (EKPG21-29, EKPG21-31), Incubation Program of National Science Foundation for Distinguished Young Scholars by Guangzhou Medical University (GMU2020-207).

Respiratory function monitoring during neonatal resuscitation: A systematic review.

Aim: Positive pressure ventilation via a facemask is critical in neonatal resuscitation, but frequently results in mask leak, obstruction, and inadequate respiratory support. This systematic review aimed to determine whether the display of respiratory function monitoring improved resuscitation or clinical outcomes. Methods: Randomized controlled trials comparing outcomes when respiratory function monitoring was displayed versus not displayed for newborns requiring positive pressure ventilation at birth were selected and from databases (last search August 2022), and assessed for risk of bias using Cochrane Risk of Bias Tools for randomized control trials. The study was registered in the Prospective Register of Systematic Reviews. Grading of Recommendations, Assessment, Development and Evaluations was used to assess the certainty of evidence. Treatment recommendations were approved by the Neonatal Life Support Task Force of the International Liaison Committee on Resuscitation. Results reported primary and secondary outcomes and included resuscitation and clinical outcomes. Results: Of 2294 unique articles assessed for eligibility, three randomized controlled trials were included (observational studies excluded) (n = 443 patients). For predefined resuscitation and clinical outcomes, these studies either did not report the primary outcome (time to heart rate ≥ 100 bpm from birth), had differing reporting methods (achieving desired tidal volumes, significant mask leak) or did not find significant differences (intubation rate, air leaks, death before hospital discharge, severe intraventricular hemorrhage, chronic lung disease). Limitations included limited sample size for critical outcomes, inconsistent definitions amongst studies and unreported long-term outcomes. Conclusion: Although respiratory function monitoring has been utilized in clinical care, there is currently insufficient evidence to suggest its benefit for newborn infants receiving respiratory support for resuscitation at birth. Registration: PROSPERO CRD42021278169 (registered November 27, 2021). Funding: The International Liaison Committee on Resuscitation provided support that included access to software platforms and teleconferencing.

Managements of sleep bruxism in adult: A systematic review.

This systematic review aimed to update the management of sleep bruxism (SB) in adults, as diagnosed using polysomnography (PSG) and/or electromyography (EMG). Management methods covered were oral appliance therapy (OAT) with stabilization splints, cognitive-behavioral therapy (CBT), biofeedback therapy (BFT), and pharmacological therapy. A comprehensive search was conducted on MEDLINE, Cochrane Library, and Web of Science up to October 1st, 2021. Reference list searches and hand searches were also performed by an external organization. Two reviewers for each therapy independently performed article selection, data extraction, and risk of bias assessment. The reviewers resolved any disagreements concerning the assortment of the articles by discussion. Finally, 11, 3, 14, and 22 articles were selected for each therapy. The results suggested that OAT tended to reduce the number of SB events, although there was no significant difference compared to other types of splints, that the potential benefits of CBT were not well supported, and that BFT, rabeprazole, clonazepam, clonidine, and botulinum toxin type A injection showed significant reductions in specific SB parameters, although several side effects were reported. It can be concluded that more methodologically rigorous randomized large-sample long-term follow-up clinical trials are needed to clarify the efficacy and safety of management for SB.

Microcurrent Therapy as a Therapeutic Modality for Musculoskeletal Pain: A Systematic Review Accelerating the Translation From Clinical Trials to Patient Care.

OBJECTIVE: To summarize the level of knowledge regarding the effects of microcurrent therapy (MCT) on musculoskeletal pain in adults. DATA SOURCES: The PubMed, Physiotherapy Evidence Database, Cumulative Index to Nursing Allied Health Literature, Cochrane Central Register of Controlled Trials, and Igaku Chuo Zasshi database were searched from the time of their inception to December 2020. STUDY SELECTION: Randomized controlled trials (RCTs) investigating the effects of MCT on musculoskeletal pain were included. Additionally, non-RCTs were included to assess the adverse events. DATA EXTRACTION: The primary outcomes were pain and adverse events related to MCT. To assess the reproducibility of MCT, we evaluated the completeness of treatment description using the Template for Intervention Description and Replication (TIDieR) checklist. We also assessed the quality of evidence using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE). DATA SYNTHESIS: A comprehensive assessment of 4 RCTs and 5 non-RCTs that met the inclusion criteria revealed that MCT significantly improved shoulder pain (1 study, 40 patients) and knee pain (1 study, 52 patients) compared with sham MCT without any severe adverse events. MCT has clinically significant benefits for knee pain. This study also revealed a clinically significant placebo response in treating knee pain. This evidence highlights the substantial effect of placebo response in clinical care. These treatment effects on knee pain are further supported by the high quality of evidence in GRADE with high reproducibility in TIDieR. CONCLUSIONS: The findings of this meta-analysis highlight the effect of placebo response in treating knee pain. MCT is a potential, core nonpharmacologic treatment option in clinical care with minimal adverse events and should be further investigated. This study proposes a framework for the future investigation of the effect of MCT on musculoskeletal pain to enhance the study quality and reproducibility.

Efficacy of pharmacologic treatment in tinnitus patients without specific or treatable origin: A network meta-analysis of randomised controlled trials.

BACKGROUND: Although tinnitus has a prevalence between 20 and 42.8%, the currently recommended management for tinnitus, such as tinnitus support and psychologic therapies, are relatively time-consuming and expensive. Several new pharmacologic treatments designed for tinnitus patients without specific origin had been developed but their efficacy remains unclear. METHODS: The current Network Meta-Analysis (NMA) of randomised controlled trials (RCTs) was conducted to evaluate the efficacy of different pharmacologic treatments for tinnitus management in tinnitus patients without specific or treatable origin (i.e. primary tinnitus). Databases were searched from inception to April 5th, 2021. All network meta-analytic procedures were conducted under the frequentist model. We calculated the effect size of outcomes with different rating scales with standardized mean difference. PROSPERO registration: CRD42020177742. FINDINGS: Overall, 36 RCTs were included with 2,761 participants. The main results revealed that pharmacologic interventions with brain-acting effect (for example, amitriptyline, acamprosate, and gabapentin) and those with anti-inflammation/anti-oxidant effect (for example, intra-tympanic dexamethasone injection plus oral melatonin) were associated with superior improvement in tinnitus severity and response rate compared to placebo/control. Oral amitriptyline were associated with the highest improvement in tinnitus severity and the fourth highest response rate. None of the investigated interventions was associated with different changes in quality of life compared to placebo/control. All the investigated treatments were associated with similar drop-out rate to placebo/control. INTERPRETATION: The current NMA suggests a potential role for treatments with brain-acting effect (for example, amitriptyline, acamprosate, and gabapentin) or anti-inflammation/anti-oxidant effect (for example, intra-tympanic dexamethasone injection plus oral melatonin) as the preferable effective treatments for tinnitus without specific or treatable origin. FUNDING: none.

The Efficacy of Fall Hazards Identification on Fall Outcomes: A Systematic Review With Meta-analysis.

OBJECTIVE: To investigate the efficacy of fall hazards identification programs when compared to no intervention or other fall prevention programs on number of falls, falls incidence, and identifying fall hazards in community-dwelling adults. DATA SOURCES: CINAHL, PubMed, EMBASE, Scopus, and PsychINFO were used to identify articles. STUDY SELECTION: Studies were selected to compare fall hazards identification programs to a control group. Studies were eligible if they were randomized controlled trials and enrolled adults older than 50 years with the incidence rate of falls as an outcome. DATA EXTRACTION: Study or authors, year, sample characteristics, intervention or comparison groups, number of falls, and number of hazards identified in the intervention and control groups, and follow-up were extracted. The risk of bias assessment was performed using the Cochrane Risk of Bias tool. Quality was evaluated with Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach per outcome. DATA SYNTHESIS: A total of 8 studies (N=8) and 5177 participants were included. There was a high risk of bias across the studies mostly due to improper blinding of personnel of the outcome assessor. Pooled estimate effects from 5 studies assessing the incidence rate of falls from 3019 individuals indicated no difference between fall hazards identification programs and control (incidence rate ratio=0.98; 95% confidence interval, 0.87-1.10). CONCLUSIONS: The current study suggests that there may be a benefit for fall hazards programs in reducing incident falls. However, because of a moderate GRADE rating, more large-scale studies with a higher number of falls events and more consistent control groups are required to determine the true effect.

Consensus on DEfinition of Food Allergy SEverity (DEFASE): Protocol for a systematic review.

BACKGROUND AND AIMS: The term "Food Allergy" refers to a complex global health problem with a wide spectrum of severity. However, a uniform definition of severe food allergy is currently missing. This systematic review is the preliminary step towards a state-of-the-art synopsis of the current evidence relating to the severity of IgE-mediated food allergy; it will inform attempts to develop a consensus to define food allergy severity by clinicians and other stakeholders. METHODS: We will undertake a systematic review, which will involve searching international biomedical databases for published studies. Studies will be independently screened against pre-defined eligibility criteria and critically appraised by established instruments. Data will be descriptively and, if possible and applicable, quantitatively synthesised. ETHICS AND DISSEMINATION: This study does not require any specific ethical approval since it is a systematic review. We plan to report results from this systematic review in a peer reviewed journal. These results will be used to inform the development of an international consensus to define severe food allergy. Author's potential conflicts of interest are clearly stated. PROSPERO REGISTRATION NUMBER: CRD42020183103.

Oral CorticoSteroid sparing with biologics in severe asthma: A remark of the Severe Asthma Network in Italy (SANI).

According to the data derived from several national and international registries, including SANI (Severe Asthma Network Italy), and considering the strong impact that frequent or regular use of oral corticosteroid has on quality of life (QoL) of severe asthmatics, as well as on the costs for managing corticosteroid-related diseases, oral corticosteroid sparing up to withdrawal should be considered a primary outcome in the management of severe asthma. New biologics have clearly demonstrated that this effect is possible, with concomitant reduction in the rate of exacerbations and in symptom control. Then, there is no reason for using so frequently oral corticosteroid before having explored all alternatives currently available for a large part of severe asthmatics.

2019 Update of Indian National Association for Study of the Liver Consensus on Prevention, Diagnosis, and Management of Hepatocellular Carcinoma in India: The Puri II Recommendations.

Hepatocellular carcinoma (HCC) is one of the major causes of morbidity, mortality, and healthcare expenditure in patients with chronic liver disease in India. The Indian National Association for Study of the Liver (INASL) had published its first guidelines on diagnosis and management of HCC (The Puri Recommendations) in 2014, and these guidelines were very well received by the healthcare community involved in diagnosis and management of HCC in India and neighboring countries. However, since 2014, many new developments have taken place in the field of HCC diagnosis and management, hence INASL endeavored to update its 2014 consensus guidelines. A new Task Force on HCC was constituted that reviewed the previous guidelines as well as the recent developments in various aspects of HCC that needed to be incorporated in the new guidelines. A 2-day round table discussion was held on 5th and 6th May 2018 at Puri, Odisha, to discuss, debate, and finalize the revised consensus statements. Each statement of the guideline was graded according to the Grading of Recommendations Assessment Development and Evaluation system with minor modifications. We present here the 2019 Update of INASL Consensus on Prevention, Diagnosis, and Management of Hepatocellular Carcinoma in India: The Puri-2 Recommendations.

Compromising between European and US allergen immunotherapy schools: Discussions from GUIMIT, the Mexican immunotherapy guidelines.

BACKGROUND: Allergen immunotherapy (AIT) has a longstanding history and still remains the only disease-changing treatment for allergic rhinitis and asthma. Over the years 2 different schools have developed their strategies: the United States (US) and the European. Allergen extracts available in these regions are adapted to local practice. In other parts of the world, extracts from both regions and local ones are commercialized, as in Mexico. Here, local experts developed a national AIT guideline (GUIMIT 2019) searching for compromises between both schools. METHODS: Using ADAPTE methodology for transculturizing guidelines and AGREE-II for evaluating guideline quality, GUIMIT selected 3 high-quality Main Reference Guidelines (MRGs): the European Academy of Allergy, Asthma and Immunology (EAACI) guideines, the S2k guideline of various German-speaking medical societies (2014), and the US Practice Parameters on Allergen Immunotherapy 2011. We formulated clinical questions and based responses on the fused evidence available in the MRGs, combined with local possibilities, patient's preference, and costs. We came across several issues on which the MRGs disagreed. These are presented here along with arguments of GUIMIT members to resolve them. GUIMIT (for a complete English version, Supplementary data) concluded the following. RESULTS: Related to the diagnosis of IgE-mediated respiratory allergy, apart from skin prick testing complementary tests (challenges, in vitro testing and molecular such as species-specific allergens) might be useful in selected cases to inform AIT composition. AIT is indicated in allergic rhinitis and suggested in allergic asthma (once controlled) and IgE-mediated atopic dermatitis. Concerning the correct subcutaneous AIT dose for compounding vials according to the US school: dosing tables and formula are given; up to 4 non-related allergens can be mixed, refraining from mixing high with low protease extracts. When using European extracts: the manufacturer's indications should be followed; in multi-allergic patients 2 simultaneous injections can be given (100% consensus); mixing is discouraged. In Mexico only allergoid tablets are available; based on doses used in all sublingual immunotherapy (SLIT) publications referenced in MRGs, GUIMIT suggests a probable effective dose related to subcutaneous immunotherapy (SCIT) might be: 50-200% of the monthly SCIT dose given daily, maximum mixing 4 allergens. Also, a table with practical suggestions on non-evidence-existing issues, developed with a simplified Delphi method, is added. Finally, dissemination and implementation of guidelines is briefly discussed, explaining how we used online tools for this in Mexico. CONCLUSIONS: Countries where European and American AIT extracts are available should adjust AIT according to which school is followed.