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 International experts in the field were also contacted for unpublished and ongoing studies.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.

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.

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.

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.

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.

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.

Allergen immunotherapy for the prevention of allergic disease: protocol for a systematic review.

BACKGROUND: The European Academy of Allergy and Clinical Immunology (EAACI) is in the process of developing the EAACI Guidelines for Allergen Immunotherapy (AIT) for the Prevention of Allergic Disease. We seek to critically assess the effectiveness, cost-effectiveness, and safety of AIT in the prevention of allergic disease. METHODS: We will undertake a systematic review, which will involve searching international biomedical databases for published, in progress and unpublished evidence. Studies will be independently screened against pre-defined eligibility criteria and critically appraised using established instruments. Data will be descriptively and, if possible and appropriate, quantitatively synthesized. DISCUSSION: The findings from this review will be used to inform the development of recommendations for EAACI's Guidelines on AIT.

Vitamin D for the management of asthma.

BACKGROUND: Several clinical trials of vitamin D to prevent asthma exacerbation and improve asthma control have been conducted in children and adults, but a meta-analysis restricted to double-blind, randomised, placebo-controlled trials of this intervention is lacking. OBJECTIVES: To evaluate the efficacy of administration of vitamin D and its hydroxylated metabolites in reducing the risk of severe asthma exacerbations (defined as those requiring treatment with systemic corticosteroids) and improving asthma symptom control. SEARCH METHODS: We searched the Cochrane Airways Group Trial Register and reference lists of articles. We contacted the authors of studies in order to identify additional trials. Date of last search: January 2016. SELECTION CRITERIA: Double-blind, randomised, placebo-controlled trials of vitamin D in children and adults with asthma evaluating exacerbation risk or asthma symptom control or both. DATA COLLECTION AND ANALYSIS: Two review authors independently applied study inclusion criteria, extracted the data, and assessed risk of bias. We obtained missing data from the authors where possible. We reported results with 95% confidence intervals (CIs). MAIN RESULTS: We included seven trials involving a total of 435 children and two trials involving a total of 658 adults in the primary analysis. Of these, one trial involving 22 children and two trials involving 658 adults contributed to the analysis of the rate of exacerbations requiring systemic corticosteroids. Duration of trials ranged from four to 12 months, and the majority of participants had mild to moderate asthma. Administration of vitamin D reduced the rate of exacerbations requiring systemic corticosteroids (rate ratio 0.63, 95% CI 0.45 to 0.88; 680 participants; 3 studies; high-quality evidence), and decreased the risk of having at least one exacerbation requiring an emergency department visit or hospitalisation or both (odds ratio (OR) 0.39, 95% CI 0.19 to 0.78; number needed to treat for an additional beneficial outcome, 27; 963 participants; 7 studies; high-quality evidence). There was no effect of vitamin D on % predicted forced expiratory volume in one second (mean difference (MD) 0.48, 95% CI -0.93 to 1.89; 387 participants; 4 studies; high-quality evidence) or Asthma Control Test scores (MD -0.08, 95% CI -0.70 to 0.54; 713 participants; 3 studies; high-quality evidence). Administration of vitamin D did not influence the risk of serious adverse events (OR 1.01, 95% CI 0.54 to 1.89; 879 participants; 5 studies; moderate-quality evidence). One trial comparing low-dose versus high-dose vitamin D reported two episodes of hypercalciuria, one in each study arm. No other study reported any adverse event potentially attributable to administration of vitamin D. No participant in any included trial suffered a fatal asthma exacerbation. We did not perform a subgroup analysis to determine whether the effect of vitamin D on risk of severe exacerbation was modified by baseline vitamin D status, due to unavailability of suitably disaggregated data. We assessed two trials as being at high risk of bias in at least one domain; neither trial contributed data to the analysis of the outcomes reported above. AUTHORS' CONCLUSIONS: Meta-analysis of a modest number of trials in people with predominantly mild to moderate asthma suggests that vitamin D is likely to reduce both the risk of severe asthma exacerbation and healthcare use. It is as yet unclear whether these effects are confined to people with lower baseline vitamin D status; further research, including individual patient data meta-analysis of existing datasets, is needed to clarify this issue. Children and people with frequent severe asthma exacerbations were under-represented; additional primary trials are needed to establish whether vitamin D can reduce the risk of severe asthma exacerbation in these groups.

Timing of Allergenic Food Introduction to the Infant Diet and Risk of Allergic or Autoimmune Disease: A Systematic Review and Meta-analysis.

IMPORTANCE: Timing of introduction of allergenic foods to the infant diet may influence the risk of allergic or autoimmune disease, but the evidence for this has not been comprehensively synthesized. OBJECTIVE: To systematically review and meta-analyze evidence that timing of allergenic food introduction during infancy influences risk of allergic or autoimmune disease. DATA SOURCES: MEDLINE, EMBASE, Web of Science, CENTRAL, and LILACS databases were searched between January 1946 and March 2016. STUDY SELECTION: Intervention trials and observational studies that evaluated timing of allergenic food introduction during the first year of life and reported allergic or autoimmune disease or allergic sensitization were included. DATA EXTRACTION AND SYNTHESIS: Data were extracted in duplicate and synthesized for meta-analysis using generic inverse variance or Mantel-Haenszel methods with a random-effects model. GRADE was used to assess the certainty of evidence. MAIN OUTCOMES AND MEASURES: Wheeze, eczema, allergic rhinitis, food allergy, allergic sensitization, type 1 diabetes mellitus, celiac disease, inflammatory bowel disease, autoimmune thyroid disease, and juvenile rheumatoid arthritis. RESULTS: Of 16 289 original titles screened, data were extracted from 204 titles reporting 146 studies. There was moderate-certainty evidence from 5 trials (1915 participants) that early egg introduction at 4 to 6 months was associated with reduced egg allergy (risk ratio [RR], 0.56; 95% CI, 0.36-0.87; I2 = 36%; P = .009). Absolute risk reduction for a population with 5.4% incidence of egg allergy was 24 cases (95% CI, 7-35 cases) per 1000 population. There was moderate-certainty evidence from 2 trials (1550 participants) that early peanut introduction at 4 to 11 months was associated with reduced peanut allergy (RR, 0.29; 95% CI, 0.11-0.74; I2 = 66%; P = .009). Absolute risk reduction for a population with 2.5% incidence of peanut allergy was 18 cases (95% CI, 6-22 cases) per 1000 population. Certainty of evidence was downgraded because of imprecision of effect estimates and indirectness of the populations and interventions studied. Timing of egg or peanut introduction was not associated with risk of allergy to other foods. There was low- to very low-certainty evidence that early fish introduction was associated with reduced allergic sensitization and rhinitis. There was high-certainty evidence that timing of gluten introduction was not associated with celiac disease risk, and timing of allergenic food introduction was not associated with other outcomes. CONCLUSIONS AND RELEVANCE: In this systematic review, early egg or peanut introduction to the infant diet was associated with lower risk of developing egg or peanut allergy. These findings must be considered in the context of limitations in the primary studies.

Effect of smoke-free legislation on perinatal and child health: a systematic review and meta-analysis.

BACKGROUND: Smoke-free legislation has the potential to reduce the substantive disease burden associated with second-hand smoke exposure, particularly in children. We investigated the effect of smoke-free legislation on perinatal and child health. METHODS: We searched 14 online databases from January, 1975 to May, 2013, with no language restrictions, for published studies, and the WHO International Clinical Trials Registry Platform for unpublished studies. Citations and reference lists of articles of interest were screened and an international expert panel was contacted to identify additional studies. We included studies undertaken with designs approved by the Cochrane Effective Practice and Organisation of Care that reported associations between smoking bans in workplaces, public places, or both, and one or more predefined early-life health indicator. The primary outcomes were preterm birth, low birthweight, and hospital attendances for asthma. Effect estimates were pooled with random-effects meta-analysis. This study is registered with PROSPERO, number CRD42013003522. FINDINGS: We identified 11 eligible studies (published 2008-13), involving more than 2·5 million births and 247,168 asthma exacerbations. All studies used interrupted time-series designs. Five North American studies described local bans and six European studies described national bans. Risk of bias was high for one study, moderate for six studies, and low for four studies. Smoke-free legislation was associated with reductions in preterm birth (four studies, 1,366,862 individuals; -10·4% [95% CI -18·8 to -2·0]; p=0·016) and hospital attendances for asthma (three studies, 225,753 events: -10·1% [95% CI -15·2 to -5·0]; p=0·0001). No significant effect on low birthweight was identified (six studies, >1·9 million individuals: -1·7% [95% CI -5·1 to 1·6]; p=0·31). INTERPRETATION: Smoke-free legislation is associated with substantial reductions in preterm births and hospital attendance for asthma. Together with the health benefits in adults, this study provides strong support for WHO recommendations to create smoke-free environments. FUNDING: Thrasher Fund, Lung Foundation Netherlands, International Paediatric Research Foundation, Maastricht University, Commonwealth Fund.

Does BCG vaccination protect against childhood asthma? Final results from the Manchester Community Asthma Study retrospective cohort study and updated systematic review and meta-analysis.

BACKGROUND: The Manchester Community Asthma Study (MANCAS) found a protective effect against the risk of wheeze at age 6 to 11 years for children given neonatal BCG vaccination. Our subsequent systematic review and meta-analysis suggested that BCG vaccination did not protect against allergic sensitization but might have exerted a protective effect against nonatopic asthma. OBJECTIVES: We sought to assess whether the protective effect of BCG vaccination on wheeze observed in the MANCAS cohort was maintained at age 13 to 17 years and to incorporate the findings from this final MANCAS analysis into an updated systematic review and meta-analysis. METHODS: BCG vaccination status was determined from health records and respiratory outcomes from questionnaire responses. We updated the systematic review and used fixed-effects and random-effects modeling to undertake meta-analyses. RESULTS: There were 1608 participants in the final MANCAS analysis. The 12-month prevalence of wheeze was 15.1%. There was no difference in prevalence between those who were and were not BCG vaccinated (15.8% vs 14.3%; relative risk, 1.05; 95% CI, 0.94-1.19). The updated meta-analysis incorporated 4 new studies: this showed that the protective effect of BCG vaccination against the development of asthma identified in our previous meta-analysis was attenuated (odds ratio, 0.95; 95% CI, 0.89-1.00). No protective effect of BCG was seen for sensitization, eczema/atopic dermatitis, rhinoconjunctivitis, or allergy in general. CONCLUSIONS: Taken together, the final results of the MANCAS cohort and the updated systematic review and meta-analysis provide clearer evidence that any protective effect of BCG vaccination on childhood asthma is likely to be transient.

Effectiveness and safety of orally administered immunotherapy for food allergies: a systematic review and meta-analysis.

The aim of using oral and sublingual immunotherapy with food allergies is to enable the safe consumption of foods containing these allergens in patients with food allergies. In the present study, a systematic review of intervention studies was undertaken; this involved the searching of eleven international databases for controlled clinical trials. We identified 1152 potentially relevant papers, from which we selected twenty-two reports of twenty-one eligible trials (i.e. eighteen randomised controlled trials and three controlled clinical trials). The meta-analysis revealed a substantially lower risk of reactions to the relevant food allergen in those receiving orally administered immunotherapy (risk ratios (RR) 0·21, 95 % CI 0·12, 0·38). The meta-analysis of immunological data demonstrated that skin prick test responses to the relevant food allergen significantly decreased with immunotherapy (mean difference - 2·96 mm, 95 % CI - 4·48, - 1·45), while allergen-specific IgG4 levels increased by an average of 19·9 (95 % CI 17·1, 22·6) µg/ml. Sensitivity analyses excluding studies at the highest risk of bias and subgroup analyses in relation to specific food allergens and treatment approaches generated comparable summary estimates of effectiveness and immunological changes. Pooling of the safety data revealed an increased risk of local (i.e. minor oropharyngeal/gastrointestinal) adverse reactions with immunotherapy (RR 1·47, 95 % CI 1·11, 1·95); there was a non-significant increased average risk of systemic adverse reactions with immunotherapy (RR 1·08, 95 % CI 0·97, 1·19). There is strong evidence that orally administered immunotherapy can induce immunomodulatory changes and thereby promote desensitisation to a range of foods. However, given the paucity of evidence on longer-term safety, effectiveness and cost-effectiveness, orally administered immunotherapy should not be used outside experimental conditions presently.

H2-antihistamines for the treatment of anaphylaxis with and without shock: a systematic review.

BACKGROUND: Anaphylaxis is a serious allergic or hypersensitivity reaction, which is rapid in onset and sometimes can prove fatal. Although H2-antihistamines are often administered for emergency treatment in anaphylaxis, there is uncertainty about their effectiveness in this disease. OBJECTIVE: To assess the benefits and harms of H2-antihistamines in the treatment of anaphylaxis. METHODS: A systematic review was performed of randomized controlled trials and quasi-randomized controlled trials comparing H2-antihistamines with placebo or no intervention in patients with anaphylaxis. RESULTS: The authors failed to identify any eligible studies for inclusion in this systematic review. CONCLUSION: When H2-antihistamines are recommended for anaphylaxis treatment, the status of the evidence base supporting their use should be described. Well-designed randomized controlled trials investigating the role of H2-antihistamines in anaphylaxis treatment are urgently needed.

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.

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.

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.