Feeding difficulties in children with food allergies: An EAACI Task Force Report.

The term "feeding difficulties" refers to a spectrum of phenotypes characterized by suboptimal intake of food and/or lack of age-appropriate eating habits. While it is evident that feeding difficulties are prevalent within healthy children, no consensus has been reached for those with food allergies. The aim of this study was to systematically review all the available literature reporting the prevalence of feeding difficulties within food allergic children. We searched eight international electronic databases for all published studies until June 2022. International experts in the field were also contacted for unpublished and ongoing studies. All publications were screened against pre-defined eligibility criteria and critically appraised by established instruments. The substantial heterogeneity of included studies precluded meta-analyses, so narrative synthesis of quantitative data was performed. A total of 2059 abstracts were assessed, out of which 21 underwent full-text screening and 10 studies met the study criteria. In these, 12 different terms to define feeding difficulties and 11 diagnostic tools were used. Five papers included data of feeding difficulty prevalence in children with food allergies, ranging from 13.6% to 40%. Higher prevalence was associated with multiple food allergies. The current literature suggests that feeding difficulties are prevalent within food allergic children, particularly those with multiple food allergies. However, the heterogeneity of terminologies and diagnostic tools makes drawing conclusions challenging. Consensus guidelines for the diagnosis and management of feeding difficulties within food allergic children and further research on the development and perpetuation of feeding difficulties are needed to appropriately manage such patients.

Clinical care of childhood sexual abuse: a systematic review and critical appraisal of guidelines from European countries.

Background: The clinical management of Child sexual abuse (CSA) demands specialised skills from healthcare professionals due to its sensitivity, legal implications, and serious physical health and mental health effects. Standardised, comprehensive clinical practice guidelines (CPGs) may be pivotal. In this systematic review, we examined existing CSA national CPGs (NCPGs) from European countries to assess their quality and reporting. Methods: We systematically searched six international databases and multiple grey literature sources, reporting by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standards. Eligible guidelines were CSA guidance from national health agencies or societies in 34 COST Action 19106 Network Countries (CANC), published between January 2012 and November 2022. Two independent researchers searched, screened, reviewed, and extracted data. NCPGs were compared for completeness with reference WHO 2017 and 2019 guidelines. We used the Appraisal of Guidelines for Research and Evaluation (AGREE II) to appraise quality and reporting. PROSPERO: CRD42022320747. Findings: Of 2919 records identified by database searches, none met inclusion criteria. Of 4714 records identified by other methods, 24 NCPGs from 17 (50%) of CANC countries were included. In 17 (50%) of eligible countries, no NCPGs were found. Content varied significantly within and between countries. NCPGs lacked many components in state-of-the art clinical practice compared to WHO reference standards, particularly in safety and risk assessment, interactions with caregivers, and mental health interventions. Appraisal by AGREE II revealed shortcomings in NCPG development, regarding scientific rigour, stakeholder involvement, implementation and evaluation. Interpretation: A notable number of European countries lack an NCPG; existing NCPGs often fall short. The healthcare response to CSA in Europe requires a coordinated approach to develop and implement high-quality CPGs. We advocate for a multidisciplinary team to develop a pan-European CSA guideline to ensure quality care for survivors. Funding: Funding was provided by the International Centre for Missing and Exploited Children.

Antibiotics Versus Placebo for Acute Bacterial Conjunctivitis: Findings From a Cochrane Systematic Review.

PURPOSE: To summarize key findings from a Cochrane review of the benefits and safety of antibiotic therapy compared with placebo (or vehicle) for acute bacterial conjunctivitis. DESIGN: Systematic review and meta-analysis. METHODS: We included placebo-controlled randomized controlled trials (RCTs) that compared topical antibiotics with placebo. We followed Cochrane methods for trial selection, data extraction, risk of bias assessment, and evidence synthesis. RESULTS: Twenty-one RCTs involving 8805 participants with acute bacterial conjunctivitis were included. Fifteen (71%) RCTs examined fluoroquinolone (FQ) drops, 3 tested macrolides, alone or in combination with steroids, and another 3 compared other non-FQ antibiotics. Intention-to-treat estimates suggested that compared with placebo, antibiotics may increase clinical recovery by 26% (risk ratio [RR]: 1.26; 95% confidence interval [CI]: 1.09-1.46) at the end of therapy (5 RCTs, 1474 participants). Modified intention-to-treat estimates, in which only participants with laboratory-confirmed bacterial conjunctivitis were analyzed, indicated that antibiotics were associated with 53% higher likelihood of microbiological cure as compared with placebo (RR: 1.53; 95% CI: 1.34-1.74; 10 RCTs, 2827 participants). Non-FQs (RR: 4.05; 95% CI: 1.36-12.00), but not FQs (RR: 0.70; 95% CI: 0.54-0.90), were likely to increase treatment-associated ocular complications such as eye pain, discomfort, and allergic reactions; the certainty of level of evidence was very low. CONCLUSIONS: Moderate level certainty of evidence suggested that antibiotics may increase the likelihood of clinical recovery and microbiological clearance compared with placebo. Very low-level certainty of evidence suggested that antibiotics may be associated with potential harm in patients with acute bacterial conjunctivitis, but the potential risk of bias from study design, inconsistency in outcome measurement, and reporting limit the evidence to very low certainty.

Consensus building on definitions and types of child maltreatment to improve recording and surveillance in Europe: protocol for a multi-sectoral, European, electronic Delphi study.

INTRODUCTION: Child maltreatment (CM) is a complex global public health issue with potentially devastating effects on individuals' physical and mental health and well-being throughout the life course. A lack of uniform definitions hinders attempts to identify, measure, respond to, and prevent CM. The aim of this electronic Delphi (e-Delphi) study is to build consensus on definitions and types of CM for use in surveillance and multi-sectoral research in the 34 countries in the Euro-CAN (Multi-Sectoral Responses to Child Abuse and Neglect in Europe) project (COST Action CA19106). METHODS AND ANALYSIS: The e-Delphi study will consist of a maximum of three rounds conducted using an online data collection platform. A multi-disciplinary expert panel consisting of researchers, child protection professionals (health and social care), police, legal professionals and adult survivors of CM will be purposefully recruited. We will approach approximately 100 experts, with between 50 and 60 of these anticipated to take part. Participants will rate their agreement with a range of statements relating to operational definitions and types of CM, and free-text comments on each of the statements to give further detail about their responses and areas of uncertainty. Consensus has been defined a priori as ≥70% of the panel agreeing or disagreeing with the statement after the final round. The responses to the open-ended questions will be analysed using a 'codebook' approach to thematic analysis, and used to refine the statements between rounds where no consensus is reached. ETHICS AND DISSEMINATION: Ethical approval has been granted from the Cardiff University School of Medicine ethics committee (reference number SMREC22/96). Results will be submitted for publication in a peer-reviewed journal and presented at workshops (including for the participants) and international academic conferences. The Euro-CAN network will also be used to disseminate the results, with results briefings and presentations to key public health and other relevant organisations in the field.

An online survey of oral health behaviours and impact on young children and families in Wales.

Introduction Studies outside Wales have consistently reported reduced quality of life as measured by the Early Childhood Oral Health Impact Scale. With relatively high levels of tooth decay in Wales as found through the regular dental surveys, it is important to understand different oral health-related behaviours and impact so that findings can inform oral health promotion in Wales.Methods An oral health questionnaire was made available to volunteers registered with Health Wise Wales. Parents of children (2-6 years old) participated in the study. Frequency analyses were carried out to understand the oral health-related behaviours and regression analysis was carried out to understand the predictors of reported oral health impacts.Results Overall reported oral health impact was low in this study. In total, 20% of parents reported that their child brushed their teeth less than twice a day and 23% reported toothbrushing without adult supervision. Drinking plain water twice a day or more was associated with good oral health in children.Conclusion Overall, reported oral health impact was low, which is likely to be due to under-representation of study participants from the deprived areas in Wales. There is plenty of room for improvement in oral health-related behaviours.

An external validation of coding for childhood maltreatment in routinely collected primary and secondary care data.

Validated methods of identifying childhood maltreatment (CM) in primary and secondary care data are needed. We aimed to create the first externally validated algorithm for identifying maltreatment using routinely collected healthcare data. Comprehensive code lists were created for use within GP and hospital admissions datasets in the SAIL Databank at Swansea University working with safeguarding clinicians and academics. These code lists build on and refine those previously published to include an exhaustive set of codes. Sensitivity, specificity and positive predictive value of previously published lists and the new algorithm were estimated against a clinically assessed cohort of CM cases from a child protection service secondary care-based setting-'the gold standard'. We conducted sensitivity analyses to examine the utility of wider codes indicating Possible CM. Trends over time from 2004 to 2020 were calculated using Poisson regression modelling. Our algorithm outperformed previously published lists identifying 43-72% of cases in primary care with a specificity ≥ 85%. Sensitivity of algorithms for identifying maltreatment in hospital admissions data was lower identifying between 9 and 28% of cases with high specificity (> 96%). Manual searching of records for those cases identified by the external dataset but not recorded in primary care suggest that this code list is exhaustive. Exploration of missed cases shows that hospital admissions data is often focused on the injury being treated rather than recording the presence of maltreatment. The absence of child protection or social care codes in hospital admissions data poses a limitation for identifying maltreatment in admissions data. Linking across GP and hospital admissions maximises the number of cases of maltreatment that can be accurately identified. Incidence of maltreatment in primary care using these code lists has increased over time. The updated algorithm has improved our ability to detect CM in routinely collected healthcare data. It is important to recognize the limitations of identifying maltreatment in individual healthcare datasets. The inclusion of child protection codes in primary care data makes this an important setting for identifying CM, whereas hospital admissions data is often focused on injuries with CM codes often absent. Implications and utility of algorithms for future research are discussed.

Current issues and challenges in the definition and operationalization of child maltreatment: A scoping review.

BACKGROUND: Studies show considerable variability in the definitions and operationalization of child maltreatment (CM), which limits research, policy formation, surveillance, and cross-country and cross-sector comparisons. OBJECTIVE: To review the recent literature (2011-2021) to understand current issues and challenges in defining CM, to assist in the planning, testing and implementing of CM conceptualizations. METHODS: We searched eight international databases. Articles were included if the substantive content was related to issues, challenges, and debates in defining CM, and the article was an original study, review, commentary, report, or guideline. The review followed methodological guidance for the conduct of scoping reviews and was reported in accordance with the PRISMA-ScR checklist. Four experts in CM conducted a thematic analysis to summarize findings. Methodological rigor of the included studies was not formally assessed. RESULTS: We identified 7372 potentially relevant articles; 55 full-text studies were assessed for eligibility, 25 satisfied the inclusion criteria. We identified three themes: 1) strategies to define CM, including the integration of child and victim perspectives; 2) difficulties in defining specific CM types; and 3) real-world implications for research, prevention and policy. CONCLUSIONS: Despite longstanding concerns, challenges regarding the definitions of CM persist. A small minority of studies have tested and implemented CM definitions and operationalizations in practice. The findings will inform international multi-sectoral processes to develop uniform definitions of CM, for example by highlighting the need to acknowledge challenges in defining some CM types and emphasizing the importance of considering the perspectives of children and CM survivors.

Appraisal of published guidelines in European countries addressing the clinical care of childhood sexual abuse: protocol for a systematic review.

INTRODUCTION: Childhood sexual abuse (CSA) is a global public health problem with potentially severe health and mental health consequences. Healthcare professionals (HCPs) should be familiar with risk factors and potential indicators of CSA, and able to provide appropriate medical management. The WHO issued global guidelines for the clinical care of children with CSA, based on rigorous review of the evidence base. The current systematic review identifies existing CSA guidelines issued by government agencies and academic societies in the European Region and assesses their quality and clarity to illuminate strengths and identify opportunities for improvement. METHODS AND ANALYSIS: This 10-database systematic review will be conducted according to the Centre for Reviews and Dissemination guidelines and will be reported according to The Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Guidance for HCPs regarding CSA, written by a national governmental agency or academic society of HCPs within 34 COST Action 19106 Network Countries (CANC) and published in peer-reviewed or grey literature between January 2012 and November 2022, is eligible for inclusion. Two independent researchers will search the international literature, screen, review and extract data. Included guidelines will be assessed for completeness and clarity, compared with the WHO 2017/2019 guidelines on CSA, and evaluated for consistency between the CANC guidelines. The Appraisal of Guidelines for Research and Evaluation II tool and Grading of Recommendations Assessment, Development and Evaluation methodology will be used to evaluate CANC guidelines. Descriptive statistics will summarise content similarities and differences between the WHO guidelines and national guidelines; data will be summarised using counts, frequencies, proportions and per cent agreement between country-specific guidelines and the WHO 2017/2019 guidelines. ETHICS AND DISSEMINATION: There are no individuals or protected health information involved and no safety issues identified. Results will be published in a peer-reviewed medical journal. PROSPERO REGISTRATION NUMBER: CRD42022320747.

WAO consensus on DEfinition of Food Allergy SEverity (DEFASE).

Background: While several scoring systems for the severity of anaphylactic reactions have been developed, there is a lack of consensus on definition and categorisation of severity of food allergy disease as a whole. Aim: To develop an international consensus on the severity of food allergy (DEfinition of Food Allergy Severity, DEFASE) scoring system, to be used globally. Methods Phase 1: We conducted a mixed-method systematic review (SR) of 11 databases for published and unpublished literature on severity of food allergy management and set up a panel of international experts. Phase 2: Based on our findings in Phase 1, we drafted statements for a two-round modified electronic Delphi (e-Delphi) survey. A purposefully selected multidisciplinary international expert panel on food allergy (n = 60) was identified and sent a structured questionnaire, including a set of statements on different domains of food allergy severity related to symptoms, health-related quality of life, and economic impact. Participants were asked to score their agreement on each statement on a 5-point Likert scale ranging from "strongly agree" to "strongly disagree". Median scores and percentage agreements were calculated. Consensus was defined a priori as being achieved if 70% or more of panel members rated a statement as "strongly agree" to "agree" after the second round. Based on feedback, 2 additional online voting rounds were conducted. Results: We received responses from 92% of Delphi panel members in round 1 and 85% in round 2. Consensus was achieved on the overall score and in all of the 5 specific key domains as essential components of the DEFASE score. Conclusions: The DEFASE score is the first comprehensive grading of food allergy severity that considers not only the severity of a single reaction, but the whole disease spectrum. An international consensus has been achieved regarding a scoring system for food allergy disease. It offers an evaluation grid, which may help to rate the severity of food allergy. Phase 3 will involve validating the scoring system in research settings, and implementing it in clinical practice.

Antibiotics versus placebo for acute bacterial conjunctivitis.

BACKGROUND: Acute bacterial conjunctivitis is an infection of the conjunctiva and is one of the most common ocular disorders in primary care. Antibiotics are generally prescribed on the basis that they may speed recovery, reduce persistence, and prevent keratitis. However, many cases of acute bacterial conjunctivitis are self-limited, resolving without antibiotic therapy. This Cochrane Review was first published in The Cochrane Library in 1999, then updated in 2006, 2012, and 2022. OBJECTIVES: To assess the benefits and side effects of antibiotic therapy in the management of acute bacterial conjunctivitis. SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2022, Issue 5), MEDLINE (January 1950 to May 2022), Embase (January 1980 to May 2022), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www. CLINICALTRIALS: gov), and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases in May 2022.   SELECTION CRITERIA: We included randomized controlled trials (RCTs) in which any form of antibiotic treatment, with or without steroid, had been compared with placebo/vehicle in the management of acute bacterial conjunctivitis. This included topical and systemic antibiotic treatments. DATA COLLECTION AND ANALYSIS: Two authors independently reviewed the titles and abstracts of identified studies. We assessed the full text of all potentially relevant studies and determined the included RCTs, which were further assessed for risk of bias using Cochrane methodology. We performed data extraction in a standardized manner and conducted random-effects meta-analyses using RevMan Web. MAIN RESULTS: We included 21 eligible RCTs, 10 of which were newly identified in this update. A total of 8805 participants were randomized. All treatments were topical in the form of drops or ointment. The trials were heterogeneous in terms of their eligibility criteria, the nature of the intervention (antibiotic drug class, which included fluoroquinolones [FQs] and non-FQs; dosage frequency; duration of treatment), the outcomes assessed and the time points of assessment. We judged one trial to be of high risk of bias, four as low risk of bias, and the others as raising some concerns. Based on intention-to-treat (ITT) population, antibiotics likely improved clinical cure (resolution of clinical symptoms or signs) by 26% (RR 1.26, 95% CI 1.09 to 1.46; 5 trials, 1474 participants; moderate certainty) as compared with placebo. Subgroup analysis showed no differences by antibiotic class (P = 0.67) or treatment duration (P = 0.60). In the placebo group, 55.5% (408/735) of participants had spontaneous clinical resolution by days 4 to 9 versus 68.2% (504/739) of participants treated with an antibiotic. Based on modified ITT population, in which participants were analyzed after randomization on the basis of positive microbiological culture, antibiotics likely increased microbiological cure (RR 1.53, 95% CI 1.34 to 1.74; 10 trials, 2827 participants) compared with placebo at the end of therapy; there were no subgroup differences by drug class (P = 0.60). No study evaluated the cost-effectiveness of antibiotic treatment. Patients receiving antibiotics had a lower risk of treatment incompletion than those in the placebo group (RR 0.64, 95% CI 0.52 to 0.78; 13 trials, 5573 participants; moderate certainty) and were 27% less likely to have persistent clinical infection (RR 0.73, 95% CI 0.65 to 0.81; 19 trials, 5280 participants; moderate certainty). There was no evidence of serious systemic side effects reported in either the antibiotic or placebo group (very low certainty). When compared with placebo, FQs (RR 0.70, 95% CI 0.54 to 0.90) but not non-FQs (RR 4.05, 95% CI 1.36 to 12.00) may result in fewer participants with ocular side effects. However, the estimated effects were of very low certainty. AUTHORS' CONCLUSIONS: The findings of this update suggest that the use of topical antibiotics is associated with a modestly improved chance of resolution in comparison to the use of placebo. Since no evidence of serious side effects was reported, use of antibiotics may therefore be considered to achieve better clinical and microbiologic efficacy than placebo. Increasing the proportion of participants with clinical cure or increasing the speed of recovery or both are important for individual return to work or school, allowing people to regain quality of life. Future studies may examine antiseptic treatments with topical antibiotics for reasons of cost and growing antibiotic resistance.

Managing food allergy: GA2LEN guideline 2022.

Food allergy affects approximately 2-4% of children and adults. This guideline provides recommendations for managing food allergy from the Global Allergy and Asthma European Network (GA2LEN). A multidisciplinary international Task Force developed the guideline using the Appraisal of Guidelines for Research and Evaluation (AGREE) II framework and the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. We reviewed the latest available evidence as of April 2021 (161 studies) and created recommendations by balancing benefits, harms, feasibility, and patient and clinician experiences. We suggest that people diagnosed with food allergy avoid triggering allergens (low certainty evidence). We suggest that infants with cow's milk allergy who need a breastmilk alternative use either hypoallergenic extensively hydrolyzed cow's milk formula or an amino acid-based formula (moderate certainty). For selected children with peanut allergy, we recommend oral immunotherapy (high certainty), though epicutaneous immunotherapy might be considered depending on individual preferences and availability (moderate certainty). We suggest considering oral immunotherapy for children with persistent severe hen's egg or cow's milk allergy (moderate certainty). There are significant gaps in evidence about safety and effectiveness of the various strategies. Research is needed to determine the best approaches to education, how to predict the risk of severe reactions, whether immunotherapy is cost-effective and whether biological therapies are effective alone or combined with allergen immunotherapy.

Allergen immunotherapy and/or biologicals for IgE-mediated food allergy: A systematic review and meta-analysis.

BACKGROUND: There is substantial interest in immunotherapy and biologicals in IgE-mediated food allergy. METHODS: We searched six databases for randomized controlled trials about immunotherapy alone or with biologicals (to April 2021) or biological monotherapy (to September 2021) in food allergy confirmed by oral food challenge. We pooled the data using random-effects meta-analysis. RESULTS: We included 36 trials about immunotherapy with 2126 mainly child participants. Oral immunotherapy increased tolerance whilst on therapy for peanut (RR 9.9, 95% CI 4.5.-21.4, high certainty); cow's milk (RR 5.7, 1.9-16.7, moderate certainty) and hen's egg allergy (RR 8.9, 4.4-18, moderate certainty). The number needed to treat to increase tolerance to a single dose of 300 mg or 1000 mg peanut protein was 2. Oral immunotherapy did not increase adverse reactions (RR 1.1, 1.0-1.2, low certainty) or severe reactions in peanut allergy (RR 1,6, 0.7-3.5, low certainty), but may increase (mild) adverse reactions in cow's milk (RR 3.9, 2.1-7.5, low certainty) and hen's egg allergy (RR 7.0, 2.4-19.8, moderate certainty). Epicutaneous immunotherapy increased tolerance whilst on therapy for peanut (RR 2.6, 1.8-3.8, moderate certainty). Results were unclear for other allergies and administration routes. There were too few trials of biologicals alone (3) or with immunotherapy (1) to draw conclusions. CONCLUSIONS: Oral immunotherapy improves tolerance whilst on therapy and is probably safe in peanut, cow's milk and hen's egg allergy. More research is needed about quality of life, cost and biologicals.

A scoping review of system-level mechanisms to prevent children being in out-of-home care.

Identifying which approaches can effectively reduce the need for out-of-home care for children is critically important. Despite the proliferation of different interventions and approaches globally, evidence summaries on this topic are limited. This study is a scoping review using a realist framework to explore what research evidence exists about reducing the number of children and young people in care. Searches of databases and websites were used to identify studies evaluating intervention effect on at least one of the following outcomes: reduction in initial entry to care; increase in family reunification post care. Data extracted from papers included type of study, outcome, type and level of intervention, effect, mechanism and moderator, implementation issues and economic (EMMIE) considerations. Data were coded by: primary outcome; level of intervention (community, policy, organisation, family or child); and type of evidence, using the realist EMMIE framework. This is the first example of a scoping review on any topic using this framework. Evaluated interventions were grouped and analysed according to system-level mechanism. We present the spread of evidence across system-level mechanisms and an overview of how each system-level mechanism might reduce the number of children in care. Implications and gaps are identified.

Risk prediction models for atherosclerotic cardiovascular disease: A systematic assessment with particular reference to Qatar.

BACKGROUND: Atherosclerotic cardiovascular disease (ASCVD) is a common disease in the State of Qatar and results in considerable morbidity, impairment of quality of life and mortality. The American College of Cardiology/American Heart Association Pooled Cohort Equations (PCE) is currently used in Qatar to identify those at high risk of ASCVD. However, it is unclear if this is the optimal ASCVD risk prediction model for use in Qatar's ethnically diverse population. AIMS: This systematic review aimed to identify, assess the methodological quality of and compare the properties of established ASCVD risk prediction models for the Qatari population. METHODS: Two reviewers performed head-to-head comparisons of established ASCVD risk calculators systematically. Studies were independently screened according to predefined eligibility criteria and critically appraised using Prediction Model Risk Of Bias Assessment Tool. Data were descriptively summarized and narratively synthesized with reporting of key statistical properties of the models. RESULTS: We identified 20,487 studies, of which 41 studies met our eligibility criteria. We identified 16 unique risk prediction models. Overall, 50% (n = 8) of the risk prediction models were judged to be at low risk of bias. Only 13% of the studies (n = 2) were judged at low risk of bias for applicability, namely, PREDICT and QRISK3.Only the PREDICT risk calculator scored low risk in both domains. CONCLUSIONS: There is no existing ASCVD risk calculator particularly well suited for use in Qatar's ethnically diverse population. Of the available models, PREDICT and QRISK3 appear most appropriate because of their inclusion of ethnicity. In the absence of a locally derived ASCVD for Qatar, there is merit in a formal head-to-head comparison between PCE, which is currently in use, and PREDICT and QRISK3.

Menopausal hormone therapy and women's health: An umbrella review.

BACKGROUND: There remains uncertainty about the impact of menopausal hormone therapy (MHT) on women's health. A systematic, comprehensive assessment of the effects on multiple outcomes is lacking. We conducted an umbrella review to comprehensively summarize evidence on the benefits and harms of MHT across diverse health outcomes. METHODS AND FINDINGS: We searched MEDLINE, EMBASE, and 10 other databases from inception to November 26, 2017, updated on December 17, 2020, to identify systematic reviews or meta-analyses of randomized controlled trials (RCTs) and observational studies investigating effects of MHT, including estrogen-alone therapy (ET) and estrogen plus progestin therapy (EPT), in perimenopausal or postmenopausal women in all countries and settings. All health outcomes in previous systematic reviews were included, including menopausal symptoms, surrogate endpoints, biomarkers, various morbidity outcomes, and mortality. Two investigators independently extracted data and assessed methodological quality of systematic reviews using the updated 16-item AMSTAR 2 instrument. Random-effects robust variance estimation was used to combine effect estimates, and 95% prediction intervals (PIs) were calculated whenever possible. We used the term MHT to encompass ET and EPT, and results are presented for MHT for each outcome, unless otherwise indicated. Sixty systematic reviews were included, involving 102 meta-analyses of RCTs and 38 of observational studies, with 102 unique outcomes. The overall quality of included systematic reviews was moderate to poor. In meta-analyses of RCTs, MHT was beneficial for vasomotor symptoms (frequency: 9 trials, 1,104 women, risk ratio [RR] 0.43, 95% CI 0.33 to 0.57, p < 0.001; severity: 7 trials, 503 women, RR 0.29, 95% CI 0.17 to 0.50, p = 0.002) and all fracture (30 trials, 43,188 women, RR 0.72, 95% CI 0.62 to 0.84, p = 0.002, 95% PI 0.58 to 0.87), as well as vaginal atrophy (intravaginal ET), sexual function, vertebral and nonvertebral fracture, diabetes mellitus, cardiovascular mortality (ET), and colorectal cancer (EPT), but harmful for stroke (17 trials, 37,272 women, RR 1.17, 95% CI 1.05 to 1.29, p = 0.027) and venous thromboembolism (23 trials, 42,292 women, RR 1.60, 95% CI 0.99 to 2.58, p = 0.052, 95% PI 1.03 to 2.99), as well as cardiovascular disease incidence and recurrence, cerebrovascular disease, nonfatal stroke, deep vein thrombosis, gallbladder disease requiring surgery, and lung cancer mortality (EPT). In meta-analyses of observational studies, MHT was associated with decreased risks of cataract, glioma, and esophageal, gastric, and colorectal cancer, but increased risks of pulmonary embolism, cholelithiasis, asthma, meningioma, and thyroid, breast, and ovarian cancer. ET and EPT had opposite effects for endometrial cancer, endometrial hyperplasia, and Alzheimer disease. The major limitations include the inability to address the varying effects of MHT by type, dose, formulation, duration of use, route of administration, and age of initiation and to take into account the quality of individual studies included in the systematic reviews. The study protocol is publicly available on PROSPERO (CRD42017083412). CONCLUSIONS: MHT has a complex balance of benefits and harms on multiple health outcomes. Some effects differ qualitatively between ET and EPT. The quality of available evidence is only moderate to poor.

Consensus on DEfinition of Food Allergy SEverity (DEFASE) an integrated mixed methods 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 undertook a mixed-methods systematic review, which involved searching 11 international biomedical databases for published studies from inception to 31 December 2019. Studies were independently screened against pre-defined eligibility criteria and critically appraised by established instruments. The substantial heterogeneity of included studies precluded meta-analyses and, therefore, narrative synthesis of quantitative and qualitative data was performed. RESULTS: We found 23 studies providing eligible primary data on symptom-specific severity of food allergic reactions, and 31 previously published symptom-severity scoring systems referred to food allergic reactions. There were seven studies which assessed quality-of-life measures in patients (and family members) with different food allergy severity and two studies that investigated the economic burden of food allergy severity. Overall, the quality and the global rating of all included studies were judged as being moderate. CONCLUSIONS: There is heterogeneity among severity scoring systems used and even outcomes considered in the context of severity of food allergy. No score has been validated. Our results will be used to inform the development of an international consensus to define the severity of food allergy. SYSTEMATIC REVIEW REGISTRATION: A protocol was prospectively registered with the International Prospective Register of Systematic Reviews (PROSPERO) database with the registration number CRD42020183103 (https://www.crd.york.ac.uk/prospero/#recordDetails).

The Use of Low-Level Laser Therapy to Reduce Postoperative Morbidity After Third Molar Surgery: A Systematic Review and Meta-Analysis.

PURPOSE: Surgical removal of third molars carries morbidity and significantly affects patients' quality-of-life. This study aims to investigate whether administration of low-level laser therapy (LLLT) is effective in reducing postoperative morbidity in patients undergoing surgical removal of mandibular third molars compared with placebo. MATERIAL AND METHODS: A systematic review and meta-analysis involving a comprehensive search strategy implemented across 5 electronic databases. This was supplemented by hand searching and contacting international experts and grey literature. Titles, abstracts, and full articles were scrutinized for studies meeting the inclusion criteria. All randomized controlled trials comparing treatment group of LLLT with a placebo control group were eligible for inclusion. The outcomes variables were postoperative pain, swelling, and trismus. Risk of bias and methodological quality assessment was carried out. We pooled data statistically, and meta-analyses were carried out using a random-effects model. RESULTS: Seventeen randomized controlled trials were included in this systematic review, all of which were considered to have a low risk of bias. Participants, aged 13 to 70 years, and 35% women, totaled 1064. Meta-analyses found significant reductions in standardized mean differences (SMDs) in swelling at day 2 and day 7 postoperatively (SMD, -0.611; 95% confidence interval, -0.968, -0.234 and SMD, -0.532; 95% confidence interval, -0.795, -0.269). There were nonsignificant reductions in SMD in pain and trismus at day 2 and day 7 postoperatively. CONCLUSIONS: LLLT significantly reduces swelling after extraction of mandibular third molars compared with placebo. LLLT has not shown to reduce postoperative pain and trismus. LLLT does not cause adverse effects. There is currently insufficient evidence available, to promote the investment in LLLT vs the net clinical benefit. Randomized controlled trials with larger sample size and standardized study design and outcome measures are required, to make definitive recommendations to clinicians on its use on patients.

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.

Intensive Family Preservation Services to prevent out-of-home placement of children: A systematic review and meta-analysis.

BACKGROUND: Intensive Family Preservation Services (IFPS) are in-home crisis intervention services designed to help families with children at imminent risk of out-of-home placement. OBJECTIVES: To assess the evidence of the effectiveness and cost-effectiveness of IFPS in reducing the need for children to enter out-of-home care. PARTICIPANTS AND SETTING: Children <18 years and their families in the home setting. METHODS: A systematic review and meta-analysis was carried out by searching 12 databases and 16 websites for publications up to January 2019. RESULTS: 1948 potentially relevant papers were identified, of which 37 papers, relating to 33 studies, met our inclusion criteria. Studies reported outcomes at child or family level. There were significant reductions in relative risk (RR) of out-of-home placements in children who received IFPS compared with controls at child level at three, six, 12 and 24 months' follow-up (RR 0.57, 95 % CI 0.35 to 0.93, RR 0.51, 95 % CI 0.27 to 0.96, RR 0.60, 95 % CI 0.48 to 0.76, RR 0.51, 95 % CI 0.30 to 0.87 respectively). At family level, there was not a significant reduction in RR of placement. Economic evidence was limited to cost analyses or cost-cost offset analyses. CONCLUSION: The available evidence, at child level, suggests that IFPS are effective in preventing children from entering care up to 24 months after the intervention. Placement outcomes reported at family level did not demonstrate a significant reduction in out-of-home placements. The economic analyses suggest that IFPS could be cost-saving; however, evidence of cost-effectiveness generated by full economic evaluations is needed.