Antibiotic exposure and the risk of colorectal adenoma and carcinoma: a systematic review and meta-analysis of observational studies.

AIM: The Incidence of colorectal cancer (CRC) is increasing, and evidence suggests that maladaptation of the bowel microbiome may be associated with colorectal carcinogenesis. Consumption of antibiotics may cause imbalance of the bowel microbiome but research assessing an association between antibiotic exposure and CRC is inconsistent. The aim of this systematic review and meta-analysis was to appraise and synthesize the available evidence. METHOD: The MEDLINE, EMBASE and CINAHL databases were searched for published observational studies. We included eight studies of 3 408 312 patients. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) for the odds of CRC following antibiotic exposure were estimated. Sensitivity analyses were performed according to exposure definition, study design and risk of bias. RESULTS: A weak association between antibiotic exposure and CRC was demonstrated when exposure was assessed cumulatively by the number of prescriptions (OR 1.204, 95% CI 1.097-1.322, P < 0.001) or duration of antibiotic exposure (OR 1.168, 95% CI 1.087-1.256, P < 0.001). Antibiotic exposure assessed as a binary variable demonstrated no association with CRC. CONCLUSION: The findings suggest a weak association between cumulative antibiotic consumption and risk of CRC but no causal conclusions can be made. Limitations include the heterogeneity and quality of the available research, particularly with regard to measurement of antibiotic exposure.

Influenza burden, prevention, and treatment in asthma-A scoping review by the EAACI Influenza in asthma task force.

To address uncertainties in the prevention and management of influenza in people with asthma, we performed a scoping review of the published literature on influenza burden; current vaccine recommendations; vaccination coverage; immunogenicity, efficacy, effectiveness, and safety of influenza vaccines; and the benefits of antiviral drugs in people with asthma. We found significant variation in the reported rates of influenza detection in individuals with acute asthma exacerbations making it unclear to what degree influenza causes exacerbations of underlying asthma. The strongest evidence of an association was seen in studies of children. Countries in the European Union currently recommend influenza vaccination of adults with asthma; however, coverage varied between regions. Coverage was lower among children with asthma. Limited data suggest that good seroprotection and seroconversion can be achieved in both children and adults with asthma and that vaccination confers a degree of protection against influenza illness and asthma-related morbidity to children with asthma. There were insufficient data to determine efficacy in adults. Overall, influenza vaccines appeared to be safe for people with asthma. We identify knowledge gaps and make recommendations on future research needs in relation to influenza in patients with asthma.

EAACI Guidelines on allergen immunotherapy: IgE-mediated food allergy.

Food allergy can result in considerable morbidity, impairment of quality of life, and healthcare expenditure. There is therefore interest in novel strategies for its treatment, particularly food allergen immunotherapy (FA-AIT) through the oral (OIT), sublingual (SLIT), or epicutaneous (EPIT) routes. This Guideline, prepared by the European Academy of Allergy and Clinical Immunology (EAACI) Task Force on Allergen Immunotherapy for IgE-mediated Food Allergy, aims to provide evidence-based recommendations for active treatment of IgE-mediated food allergy with FA-AIT. Immunotherapy relies on the delivery of gradually increasing doses of specific allergen to increase the threshold of reaction while on therapy (also known as desensitization) and ultimately to achieve post-discontinuation effectiveness (also known as tolerance or sustained unresponsiveness). Oral FA-AIT has most frequently been assessed: here, the allergen is either immediately swallowed (OIT) or held under the tongue for a period of time (SLIT). Overall, trials have found substantial benefit for patients undergoing either OIT or SLIT with respect to efficacy during treatment, particularly for cow's milk, hen's egg, and peanut allergies. A benefit post-discontinuation is also suggested, but not confirmed. Adverse events during FA-AIT have been frequently reported, but few subjects discontinue FA-AIT as a result of these. Taking into account the current evidence, FA-AIT should only be performed in research centers or in clinical centers with an extensive experience in FA-AIT. Patients and their families should be provided with information about the use of FA-AIT for IgE-mediated food allergy to allow them to make an informed decision about the therapy.

Allergen immunotherapy for IgE-mediated food allergy: a systematic review and meta-analysis.

BACKGROUND: The European Academy of Allergy and Clinical Immunology (EAACI) is developing Guidelines for Allergen Immunotherapy (AIT) for IgE-mediated Food Allergy. To inform the development of clinical recommendations, we sought to critically assess evidence on the effectiveness, safety and cost-effectiveness of AIT in the management of food allergy. METHODS: We undertook a systematic review and meta-analysis that involved searching nine international electronic databases for randomized controlled trials (RCTs) and nonrandomized studies (NRS). Eligible studies were independently assessed by two reviewers against predefined eligibility criteria. The quality of studies was assessed using the Cochrane Risk of Bias tool for RCTs and the Cochrane ACROBAT-NRS tool for quasi-RCTs. Random-effects meta-analyses were undertaken, with planned subgroup and sensitivity analyses. RESULTS: We identified 1814 potentially relevant papers from which we selected 31 eligible studies, comprising of 25 RCTs and six NRS, studying a total of 1259 patients. Twenty-five trials evaluated oral immunotherapy (OIT), five studies investigated sublingual immunotherapy, and one study evaluated epicutaneous immunotherapy. The majority of these studies were in children. Twenty-seven studies assessed desensitization, and eight studies investigated sustained unresponsiveness postdiscontinuation of AIT. Meta-analyses demonstrated a substantial benefit in terms of desensitization (risk ratio (RR) = 0.16, 95% CI 0.10, 0.26) and suggested, but did not confirm sustained unresponsiveness (RR = 0.29, 95% CI 0.08, 1.13). Only one study reported on disease-specific quality of life (QoL), which reported no comparative results between OIT and control group. Meta-analyses revealed that the risk of experiencing a systemic adverse reaction was higher in those receiving AIT, with a more marked increase in the risk of local adverse reactions. Sensitivity analysis excluding those studies judged to be at high risk of bias demonstrated the robustness of summary estimates of effectiveness and safety of AIT for food allergy. None of the studies reported data on health economic analyses. CONCLUSIONS: AIT may be effective in raising the threshold of reactivity to a range of foods in children with IgE-mediated food allergy whilst receiving (i.e. desensitization) and post-discontinuation of AIT. It is, however, associated with a modest increased risk in serious systemic adverse reactions and a substantial increase in minor local adverse reactions. More data are needed in relation to adults, long term effects, the impact on QoL and the cost-effectiveness of AIT.

Allergen immunotherapy for allergic rhinoconjunctivitis: A systematic review and meta-analysis.

BACKGROUND: The European Academy of Allergy and Clinical Immunology (EAACI) is in the process of developing Guidelines on Allergen Immunotherapy (AIT) for Allergic Rhinoconjunctivitis. To inform the development of clinical recommendations, we undertook a systematic review to assess the effectiveness, cost-effectiveness, and safety of AIT in the management of allergic rhinoconjunctivitis. METHODS: We searched nine international biomedical databases for published, in-progress, and unpublished evidence. Studies were independently screened by two reviewers against predefined eligibility criteria and critically appraised using established instruments. Our primary outcomes of interest were symptom, medication, and combined symptom and medication scores. Secondary outcomes of interest included cost-effectiveness and safety. Data were descriptively summarized and then quantitatively synthesized using random-effects meta-analyses. RESULTS: We identified 5960 studies of which 160 studies satisfied our eligibility criteria. There was a substantial body of evidence demonstrating significant reductions in standardized mean differences (SMD) of symptom (SMD -0.53, 95% CI -0.63, -0.42), medication (SMD -0.37, 95% CI -0.49, -0.26), and combined symptom and medication (SMD -0.49, 95% CI -0.69, -0.30) scores while on treatment that were robust to prespecified sensitivity analyses. There was in comparison a more modest body of evidence on effectiveness post-discontinuation of AIT, suggesting a benefit in relation to symptom scores. CONCLUSIONS: AIT is effective in improving symptom, medication, and combined symptom and medication scores in patients with allergic rhinoconjunctivitis while on treatment, and there is some evidence suggesting that these benefits are maintained in relation to symptom scores after discontinuation of therapy.

H1-antihistamines for primary mast cell activation syndromes: a systematic review.

BACKGROUND: Primary mast cell activation syndromes (MCAS) are a group of disorders presenting with symptoms of mast cell mediator release. OBJECTIVES: To assess the effectiveness and safety of orally administered H1 -antihistamines in the treatment of primary MCAS compared with placebo and other pharmacologic treatments. METHODS: We systematically searched five databases and three trial repositories and contacted an international panel of experts to identify published and unpublished trials. RESULTS: A total of 36 potentially relevant studies were identified. Of these, five crossover trials, enrolling a total of 71 patients (63 adults), met the eligibility criteria. All five of these studies were judged to be at moderate or high risk of bias. Two studies compared an H1 -antihistamine with placebo, two compared two different H1 -antihistamines, and one study compared H1 - and H2 -antihistamines with oral cromolyn sodium. Four of the five randomized controlled trials were historic (reported from 1983-1993), small (enrolling 8-15 patients), and used agents and/or dosing regimens that are now less commonly used in clinical practice (i.e. azelastine, chlorpheniramine, hydroxyzine, and ketotifen). The fifth trial, which enrolled 33 adults with cutaneous and systemic mastocytosis found 4 weeks of treatment with the second-generation H1 -antihistamine rupatadine, compared with placebo, resulted in significant improvements in quality of life, symptom control (itching, wheals and flares, flushing, tachycardia, and headache, but not gastrointestinal symptoms), and reduction in itching and whealing after standardized skin provocation to elicit Darier's sign. CONCLUSIONS: There is an urgent need for large, well-designed, double-blind, placebo-controlled randomized trials investigating the effectiveness, cost-effectiveness, and safety of second-generation H1 -antihistamines in treatment of primary MCAS.

Confounding and effect modification in studies of diet and childhood asthma and allergies.

OBJECTIVE: To propose a comprehensive set of confounders and effect modifiers that should be considered in epidemiologic investigations. METHODS: Two reviewers independently critiqued studies included in a recent systematic review and extracted data on the confounders and effect modifiers that were considered and the approaches used to justify inclusion. RESULTS: Of the 62 studies reviewed, 20 were cohort, 16 case-control, 25 cross-sectional studies, and one ecologic study. All cohort, cross-sectional, and ecologic studies had some adjustment for confounding or consideration of effect modification, but this was only the case for 7/16 (44%) case-control studies. Of the 53 studies that considered confounding or effect modification, 39/53 (74%) gave no justification for the inclusion of the variables considered. Studies that justified the inclusion of the variables did so based on empirical evidence (n = 10), conceptual justification (n = 7), or a combination of the two (n = 3). Confounding was handled mainly by using regression modeling, but some case-control studies utilized matching and anova. Ten studies handled effect modification by stratification, eight tested for interaction, and five used both strategies. CONCLUSIONS: We have found substantial shortcomings in the handling of confounding and effect modification in studies of diet and development of childhood asthma/allergies. Selection of variables should be based on conceptual considerations and empirical evidence. Using this approach, we have proposed a comprehensive set of confounders and effect modifiers that need to be considered in future studies.

House dust mite avoidance measures for perennial allergic rhinitis: an updated Cochrane systematic review.

BACKGROUND: To assess the benefits and harms of measures designed to reduce house dust mite (HDM) exposure in the management of house dust mite-sensitive allergic rhinitis. METHODS: Systematic review of randomized controlled trials was made, in which HDM control measures have been evaluated in comparison with placebo or other HDM avoidance measures, in patients with clinically proven allergic rhinitis. RESULTS: Nine trials involving 501 participants satisfied the inclusion criteria. These trials have investigated the effectiveness of bedroom environmental control programmes involving the use of HDM impermeable bedding covers (n = 4), acaricides (n = 2), high-efficiency particulate air filters (n = 2) and, using a factorial design, acaricide and HDM impermeable bedding covers in isolation and combination (n = 1). Seven of the nine trials reported that, when compared with control, the interventions studied resulted in significant reductions in HDM load. Of the interventions studied to date, acaricides appear to be the most promising, although the findings from these studies need to be interpreted with care because of their methodological limitations. House dust mite impermeable bedding as an isolated intervention is unlikely to offer benefit. CONCLUSIONS: Trials have tended to be small and of poor methodological quality, making it difficult to offer any definitive recommendations. Interventions that achieve substantial reductions in HDM load may offer some benefit in reducing rhinitis symptoms. Isolated use of HDM impermeable bedding is unlikely to prove effective.

Is the prevalence of asthma declining? Systematic review of epidemiological studies.

Asthma prevalence has increased very considerably in recent decades such that it is now one of the commonest chronic disorders in the world. Recent evidence from epidemiological studies, however, suggests that the prevalence of asthma may now be declining in many parts of the world, which, if true is important for health service planning and also because this offers the possibility of generating and testing new aetiological hypotheses. Our objective was to determine whether the prevalence of asthma is declining worldwide. We undertook a systematic search of EMBASE, Medline, Web of Science and Google Scholar, for high quality reports of cohort studies, repeat cross-sectional studies and analyses of routine healthcare datasets to examine international trends in asthma prevalence in children and adults for the period 1990-2008. There were 48 full reports of studies that satisfied our inclusion criteria. The large volume of data identified clearly indicate that there are, at present, no overall signs of a declining trend in asthma prevalence; on the contrary, asthma prevalence is in many parts of the world still increasing. The reductions in emergency healthcare utilization being reported in some economically developed countries most probably reflect improvements in quality of care. There remain major gaps in the literature on asthma trends in relation to Africa and parts of Asia. There is no overall global downward trend in the prevalence of asthma. Healthcare planners will for the foreseeable future, therefore, need to continue with high levels of anticipated expenditure in relation to provision of asthma care.

Omega 3 and 6 oils for primary prevention of allergic disease: systematic review and meta-analysis.

BACKGROUND: There is conflicting evidence on the use of omega 3 and omega 6 supplementation for the prevention of allergic diseases. We conducted a systematic review evaluating the effectiveness of omega 3 and 6 oils for the primary prevention of sensitization and development of allergic disorders. METHODS: We searched The Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, LILACS, PsycInfo, AMED, ISI Web of Science and Google Scholar for double-blind randomized controlled trials. Two authors independently assessed articles for inclusion. Meta-analyses were undertaken using fixed effects modelling, or random effects modelling in the event of detecting significant heterogeneity. RESULTS: Of the 3129 articles identified, 10 reports (representing six unique studies) satisfied the inclusion criteria. Four studies compared omega 3 supplements with placebo and two studies compared omega 6 supplements with placebo. There was no clear evidence of benefit in relation to reduced risk of allergic sensitization or a favourable immunological profile. Meta-analyses failed to identify any consistent or clear benefits associated with use of omega 3 [atopic eczema: RR = 1.10 (95% CI 0.78-1.54); asthma: RR = 0.81 (95% CI 0.53-1.25); allergic rhinitis: RR = 0.80 (95% CI 0.34-1.89) or food allergy RR = 0.51 (95% CI 0.10-2.55)] or omega 6 oils [atopic eczema: RR = 0.80 (95% CI 0.56-1.16)] for the prevention of clinical disease. CONCLUSIONS: Contrary to the evidence from basic science and epidemiological studies, our systematic review and meta-analysis suggests that supplementation with omega 3 and omega 6 oils is probably unlikely to play an important role as a strategy for the primary prevention of sensitization or allergic disease.

[Endocrine response to extracorporeal circulation]. / Endokrinnyi otvet na iskusstvennoe krovoobrashchenie.

The authors analyze the results of measuring the content of vasopressin, renin, angiotensin II and aldosterone coupled with the results of studying hemodynamics, acid-base state, and lactate in the arterial blood during operations on the heart in 32 patients with different acquired heart diseases. The main attention was concentrated on studies into the nature of humoral changes during extracorporeal circulation in three types of anesthesia. In group I, anesthesia was maintained by fentanyl given in a dose of 5-6 micrograms/kg/h, diazepam (0.1 mg/kg/h), and arduan (0.02 mg/kg/h). In the second observation group, at the beginning of perfusion the patients were administered trimetotan (artonad) (0.2 mg/kg), and in group III, the dose of fentanyl was raised during perfusion to 10-12 micrograms/kg/h. It is concluded that during extracorporeal circulation, it is desirable that the dose of fentanyl be increased to attain more adequate anesthesia in that period of heart surgery. The magnitude of humoral changes occurring in the body during extracorporeal circulation served as a criterion for anesthesia adequacy.