The current use of the EORTC QLQ-NMIBC24 and QLQ-BLM30 questionnaires for the assessment of health-related quality of life in bladder cancer patients: a systematic review.

PURPOSE: Investigating the use of the EORTC bladder cancer (BC) modules by evaluating: (a) study contexts/designs; (b) languages/countries in which the modules were administered; (c) their acceptance by patients/investigators; and (d) their psychometric properties. METHODS: A systematic review was performed with studies from 1998 until 20/10/2021 in five databases. Articles/conference abstracts using the EORTC-QLQBLM30 (muscle invasive BC) and the EORTC-QLQNMIBC24 (previously referred to as QLQ-BLS24; non-muscle invasive BC) were included. Two authors independently screened titles/abstracts/full-texts and performed data extraction. RESULTS: A total of 76 eligible studies were identified. Most studies included the BLM30 (n = 53), were in a urological surgery context (n = 41) and were cross-sectional (n = 35) or prospective (n = 30) in design. The BC modules were administered in 14 languages across 19 countries. Missing data were low-moderate for all non-sex related questions (< 1% to 15%). Sex-related questions had higher rates of missing data (ranging from 6.9% to 84%). Most investigators did not use all scales of the questionnaires. One validation study for the original BLS24 led to the development of the NMIBC24, which adopted a new scale structure for which good structural validity was confirmed (n = 3). Good reliability and validity was shown for the NMIBC24 module, except for malaise and bloating/flatulence scales. Psychometric evidence for BLM30 is lacking. CONCLUSION: These results provide insight into how the EORTC BC quality of life modules could be further improved. Current work is ongoing to update the modules and to determine if the two modules can be combined into a single questionnaire that works well in both the NMIBC and MIBC settings.

Stapled intestinal anastomoses are more cost effective than hand-sewn anastomoses in a diagnosis related group system.

PURPOSE: Creation of an optimal bowel anastomosis with low postoperative leakage rate is an immanent part of colorectal surgery contributing to recovery, length of hospital stay and overall hospital costs. We aimed to investigate costs of small and large bowel resection, length of hospital stay, anastomotic leakage rate and its risk factors depending on the anastomotic technique. METHODS: Retrospective analysis of 198 patients (67 stapled and 131 hand-sewn anastomoses) undergoing elective bowel resection with a single anastomosis without protective ileostomy either stapled or in double-rowed running suture technique between 1st October 2012 and 30th September 2018 at Charité University Hospital Berlin, Campus Benjamin Franklin. We analyzed costs of treatment, total length of hospital stay, rate of anastomotic leakage and possible risk factors for anastomotic leak. RESULTS: No significant difference between both anastomotic techniques could be detected for hospital stay (p = 0.754), 30-day-readmission rate (p = 0.827), or anastomotic leakage (p = 606). Neither comorbidities (p = 0.449), underlying disease (p = 0.132), experience of the surgical team (p = 0.828) nor scheduling of the operation (p = 0.531) were associated with anastomotic leakage. Stapled anastomoses took 22 min less operation time than sutured anastomoses (130 vs. 152 min. Median) (p = 0.001). Operations with stapled anastomoses saved 183 € in operation costs and 496 € in overall hospital costs. CONCLUSION: Stapled and hand-sewn bowel anastomoses can be performed equally safe without differences in postoperative outcome. No patient, procedure or surgeon related risk factors for anastomotic leakage could be detected. Bowel resections with stapled anastomoses take less time and save operation and overall hospital costs.

[Diagnostic and therapeutic approach to anaphylaxis in childhood and adolescence]. / Diagnostisches und therapeutisches Vorgehen bei Anaphylaxie im Kindes- und Jugendalter.

Anaphylaxis is a suddenly occurring potentially life-threatening systemic allergic reaction. In childhood, food allergens play a major role but insect stings and drugs are also potential triggers. The symptoms appear in minutes up to few hours on the skin, airways, gastrointestinal tract and/or the cardiovascular system. Intramuscular adrenaline is the drug of first choice due to its rapid effectiveness and its low side effect potential. A detailed patient history and the determination of potential IgE antibodies must be carried out to identify the triggers. The register for anaphylaxis has improved knowledge on epidemiology. An education in anaphylaxis is useful for every patient as well as parents and caregivers. Allergen-specific immunotherapy is currently the only causal treatment option; however, at the present time it is only available for insect bites and peanut allergy.

Facilitators of behavior change and weight loss in an intervention for African American Breast Cancer Survivors.

PURPOSE: The purpose of this study was to examine facilitators of behavior change and weight loss among African-American women who participated in the Moving Forward Efficacy trial. METHODS: Linear mixed models were used to examine the role of self-efficacy, social support, and perceived access to healthy eating, exercise, and neighborhood safety on weight, physical activity, and diet. We also examined the mediation of self-efficacy, social support, and perceived access to healthy eating, exercise, and neighborhood safety on weight loss, physical activity, and diet using the Freedman Schatzkin statistic. RESULTS: We found no evidence to suggest mediation, but some direct associations of self-efficacy, certain types of social support and perceived access to exercise on weight loss, and behavior change. CONCLUSION: We determined that self-efficacy, social support, and perceived access to exercise played a role in weight loss, increased MVPA, and better diet. The role of self-efficacy and perceived access to exercise were more consistent than social support.

Novel methods for in vitro modeling of pancreatic cancer reveal important aspects for successful primary cell culture.

BACKGROUND: Pancreatic cancer remains a fatal disease. Experimental systems are needed for personalized treatment strategies, drug testing and to further understand tumor biology. Cell cultures can serve as an excellent preclinical platform, but their generation remains challenging. METHODS: Tumor cells from surgically removed pancreatic ductal adenocarcinoma (PDAC) specimens were cultured under novel protocols. Cellular growth and composition were analyzed and culture conditions were continuously optimized. Characterization of cell cultures and primary tumors was performed via hematoxylin and eosin (HE) and immunofluorescence (IF) staining. RESULTS: Protocols for two- and three-dimensional PDAC primary cell cultures could successfully be established. Primary cell culture depended on dissociation techniques, growth factor supplementation and extracellular matrix components containing Matrigel being crucial for the transformation to three-dimensional PDAC organoids. The generated cultures showed to be highly resemblant to established PDAC primary cell cultures. HE and IF staining for cell culture and corresponding primary tumor characterization could successfully be performed. CONCLUSIONS: The work presented herein shows novel and effective methods to successfully establish primary PDAC cell cultures in a distinct time frame. Factors contributing to cell growth and differentiation could be identified with important implications for further primary cell culture protocols. The established protocols might serve as novel tools in personalized tumor therapy.

Colectomy with ileostomy for severe ulcerative colitis-postoperative complications and risk factors.

PURPOSE: In the era of biological therapy of ulcerative colitis (UC), surgical treatment frequently consists of colectomy, end ileostomy, and rectal stump closure before patients go on towards restorative proctocolectomy. We aimed to evaluate possible risk factors for the occurrence of postoperative complications and investigate those after initial colectomy in these patients. METHODS: Retrospective analysis of 180 patients (76 female, 104 male) undergoing colectomy for UC with formation of a rectal stump and terminal ileostomy between March 2008 and March 2018 at Charité University Hospital Berlin, Campus Benjamin Franklin. A panel of possible postoperative complications was established, patient history was screened, and postoperative complications were analyzed using the Clavien Dindo Classification. RESULTS: Postoperative complication rate was 27.7%. Mortality was 0.5%. Postoperative ileus occurred in 15.3% and rectal stump leakage in 14.8%. Complications were categorized as Clavien Dindo 3 in 80%. Risk factors for surgical complications after multivariate analysis were ASA classification (p = 0.004), preoperative anemia (Hemoglobin < 8 mg/dl) (p = 0.025), use of immunosuppressants (p = 0.003), more than two cardiovascular diseases (p = 0.016), and peritonitis (p = 0.000). Reoperation rate of patients with surgical complications was 27.7%. CONCLUSION: Colectomy in high-risk UC patients is associated with significant morbidity. However, most of the surgical complications can be treated conservatively. Overall mortality is low. Patient-related risk factors are associated with postoperative complications. Optimizing these risk factors or earlier indication for surgery in the course of UC may help to reduce morbidity of this procedure.

Hen's egg allergen in house and bed dust is significantly increased after hen's egg consumption-A pilot study.

Environmental exposure to food allergens may be a risk factor for cutaneous sensitization. Previous studies could detect peanut allergen in house dust. In this pilot study, we wanted to investigate whether hen's egg allergen is detectable in house dust collected from different household areas and whether levels are increased after intentional hen's egg consumption. Hen's egg protein levels of dust samples were measured using ELISA. In 8 of 8 households, hen's egg was detectable in dust samples of eating area and bed. Forty-eight hours after intentional hen's egg consumption, hen's egg protein levels were significantly increased in both. Still, further research is necessary to investigate whether hen's egg allergen in house and bed dust plays a role in sensitization via skin.

Fish oil in infancy protects against food allergy in Iceland-Results from a birth cohort study.

BACKGROUND: Consumption of oily fish or fish oil during pregnancy, lactation and infancy has been linked to a reduction in the development of allergic diseases in childhood. METHODS: In an observational study, Icelandic children (n = 1304) were prospectively followed from birth to 2.5 years with detailed questionnaires administered at birth and at 1 and 2 years of age, including questions about fish oil supplementation. Children with suspected food allergy were invited for physical examinations, allergic sensitization tests, and a double-blind, placebo-controlled food challenge if the allergy testing or clinical history indicated food allergy. The study investigated the development of sensitization to food and confirmed food allergy according to age and frequency of postnatal fish oil supplementation using proportional hazards modelling. RESULTS: The incidence of diagnosed food sensitization was significantly lower in children who received regular fish oil supplementation (relative risk: 0.51, 95% confidence interval: 0.32-0.82). The incidence of challenge-confirmed food allergy was also reduced, although not statistically significant (0.57, 0.30-1.12). Children who began to receive fish oil in their first half year of life were significantly more protected than those who began later (P = .045 for sensitization, P = .018 for allergy). Indicators of allergy severity decreased with increased fish oil consumption (P = .013). Adjusting for parent education and allergic family history did not change the results. CONCLUSION: Postnatal fish oil consumption is associated with decreased food sensitization and food allergies in infants and may provide an intervention strategy for allergy prevention.

How does dose impact on the severity of food-induced allergic reactions, and can this improve risk assessment for allergenic foods?: Report from an ILSI Europe Food Allergy Task Force Expert Group and Workshop.

Quantitative risk assessment (QRA) for food allergens has made considerable progress in recent years, yet acceptability of its outcomes remains stymied because of the limited extent to which it has been possible to incorporate severity as a variable. Reaction severity, particularly following accidental exposure, depends on multiple factors, related to the allergen, the host and any treatments, which might be administered. Some of these factors are plausibly still unknown. Quantitative risk assessment shows that limiting exposure through control of dose reduces the rates of reactions in allergic populations, but its impact on the relative frequency of severe reactions at different doses is unclear. Food challenge studies suggest that the relationship between dose of allergenic food and reaction severity is complex even under relatively controlled conditions. Because of these complexities, epidemiological studies provide very limited insight into this aspect of the dose-response relationship. Emerging data from single-dose challenges suggest that graded food challenges may overestimate the rate of severe reactions. It may be necessary to generate new data (such as those from single-dose challenges) to reliably identify the effect of dose on severity for use in QRA. Success will reduce uncertainty in the susceptible population and improve consumer choice.

The urgent need for a harmonized severity scoring system for acute allergic reactions.

The accurate assessment and communication of the severity of acute allergic reactions are important to patients, clinicians, researchers, the food industry, and public health and regulatory authorities. Severity has different meanings to different stakeholders with patients and clinicians rating the significance of particular symptoms very differently. Many severity scoring systems have been generated, most focusing on the severity of reactions following exposure to a limited group of allergens. They are heterogeneous in format, none has used an accepted developmental approach, and none has been validated. Their wide range of outcome formats has led to difficulties with interpretation and application. Therefore, there is a persisting need for an appropriately developed and validated severity scoring system for allergic reactions that work across the range of allergenic triggers and address the needs of different stakeholder groups. We propose a novel approach to develop and then validate a harmonized scoring system for acute allergic reactions, based on a data-driven method that is informed by clinical and patient experience and other stakeholders' perspectives. We envisage two formats: (i) a numerical score giving a continuum from mild to severe reactions that are clinically meaningful and are useful for allergy healthcare professionals and researchers, and (ii) a three-grade-based ordinal format that is simple enough to be used and understood by other professionals and patients. Testing of reliability and validity of the new approach in a range of settings and populations will allow eventual implementation of a standardized scoring system in clinical studies and routine practice.

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.

Randomized study of the influence of two-dimensional versus three-dimensional imaging using a novel 3D head-mounted display (HMS-3000MT) on performance of laparoscopic inguinal hernia repair.

BACKGROUND: 3D laparoscopy has proven to be superior to the 2D approach in experimental settings. The aim of the present study was to investigate the influence of 3D laparoscopy using a novel head-mounted display on the performance of defined steps within a laparoscopic inguinal hernia repair. This effect was investigated both in laparoscopically advanced surgeons and in beginners. METHODS: Patients suffering from symptomatic inguinal hernia were randomly assigned to laparoscopic hernia repair using either a head-mounted 3D display or a conventional 2D laparoscopic approach. Operative performance of both groups was compared in terms of the time taken for mesh placement and for peritoneal suturing. Additionally, quality of imaging and physical discomfort were assessed. RESULTS: The use of a head-mounted 3D display was able to shorten the time required for placement of the mesh as well as that for peritoneal suturing, both for experienced and novice surgeons when compared to the conventional 2D approach. 3D laparoscopy was significantly superior to 2D laparoscopy in terms of depth perception, image sharpness and image contrast. Additionally, increased impairment caused by ghosting effects could not be detected in 3D laparoscopy. Evaluation of image quality was independent of experience in laparoscopic surgery. However, use of a head-mounted 3D display resulted in a significant impairment of surgeon's comfort when compared to 2D laparoscopy. Thereby, the greatest impairment was caused by ear discomfort. CONCLUSIONS: This is the first study examining the effect of a head-mounted 3D system on the performance of laparoscopy in a randomized controlled trial (RCT) showing a clear advantage of this system in surgical performance as well as in depth perception and image quality.

Performance of a polymer coated silicon microarray for simultaneous detection of food allergen-specific IgE and IgG4.

BACKGROUND: Microarray-based component-resolved diagnostics (CRD) has become an accepted tool to detect allergen-specific IgE sensitization towards hundreds of allergens in parallel from one drop of serum. Nevertheless, specificity and sensitivity as well as a simultaneous detection of allergen-specific IgG4 , as a potential parameter for tolerance development, remain to be optimized. OBJECTIVE: We applied the recently introduced silicon chip coated with a functional polymer named copoly(DMA-NAS-MAPS) to the simultaneous detection of food allergen-specific IgE and IgG4 , and compared it with ImmunoCAP and ImmunoCAP ISAC. Inter- and intraslide variation, linearity of signal and working range, sensitivity and application of internal calibrations for IgE and IgG4 were assessed. METHODS: Native and recombinant allergenic proteins from hen's egg and cow's milk were spotted on silicon chips coated with copoly(DMA-NAS-MAPS) along with known concentrations for human IgE and IgG4 . A serum pool and 105 patient samples were assessed quantitatively and semi-quantitatively with the ImmunoCAP and ImmunoCAP ISAC and correlated with IgE- and IgG4 -specific fluorescence on silicon microarrays. RESULTS: Allergen-specific IgE and IgG4 were detected in parallel using two fluorescent dyes with no crosstalk. Results from the ImmunoCAP correlated better with microarray fluorescence than with ImmunoCAP ISAC except for the allergen ovomucoid. The working range of the silicon microarray for total hen's egg-specific IgE was comparable to the range of 0.1 to >100 kUA /L of the ImmunoCAP system, whereas for total cow's milk, the silicon microarray was less sensitive. Detectable allergen-specific IgG4 could be determined only for low concentrations, but still correlated positively with ImmunoCAP results. CONCLUSIONS: We confirmed the ability of the polymer coated silicon microarray to be comparably sensitive to the ImmunoCAP ISAC for various food allergens. This suggests that the copoly(DMA-NAS-MAPS) microarray is a low-cost, self-producible alternative to the commercial ImmunoCAP ISAC in allergy research.

Genomewide association study of peanut allergy reproduces association with amino acid polymorphisms in HLA-DRB1.

BACKGROUND: Genetic variants for IgE-mediated peanut allergy are yet to be fully characterized and to date only one genomewide association study (GWAS) has been published. OBJECTIVE: To identify genetic variants associated with challenge-proven peanut allergy. METHODS: We carried out a GWAS comparing 73 infants with challenge-proven IgE-mediated peanut allergy against 148 non-allergic infants (all ~ 1 year old). We tested a total of 3.8 million single nucleotide polymorphisms, as well as imputed HLA alleles and amino acids. Replication was assessed by de novo genotyping in a panel of additional 117 cases and 380 controls, and in silico testing in two independent GWAS cohorts. RESULTS: We identified 21 independent associations at P ≤ 5 × 10-5 but were unable to replicate these. The most significant HLA association was the previously reported amino acid variant located at position 71, within the peptide-binding groove of HLA-DRB1 (P = 2 × 10-4 ). Our study therefore reproduced previous findings for the association between peanut allergy and HLA-DRB1 in this Australian population. CONCLUSIONS AND CLINICAL RELEVANCE: Genetic determinants for challenge-proven peanut allergy include alleles at the HLA-DRB1 locus.

Natural tolerance development in cow's milk allergic children: IgE and IgG4 epitope binding.

BACKGROUND: Although most of cow's milk (CM) allergic children will outgrow their allergy, the pathomechanism of the natural development of tolerance remains poorly understood. It has been suggested that the balance between milk-specific IgE and IgG4 plays a major role. OBJECTIVE: We aimed to investigate differences in IgE and IgG4 antibody binding to CM epitopes between patients with persistent CM allergy (CMA) and those that naturally became tolerant. METHODS: Sera from 35 children with proven CMA (median age at inclusion of 10 months) were analyzed retrospectively; 22 patients have become tolerant (median age at tolerance acquisition of 51 months) during the study period as confirmed by a negative oral food challenge. IgE and IgG4 binding to sequential epitopes derived from five major CM proteins were measured with a peptide microarray-based immunoassay. RESULTS: At baselines, greater intensity and broader diversity of IgE and IgG4 binding have been found in children with persistent CMA beyond 5 years of age compared to patients with transient CMA. Moreover, children with transient CMA had IgE and IgG4 antibodies that more often recognized the same epitopes, compared to those with persistent CMA. From baseline to the time of tolerance development, both IgE and IgG4 binding intensity decreased significantly, particularly in areas of α-s- and ß-casein (P<.01, false discovery rate [FDR]<.1). Interestingly, differences between IgE and IgG4 binding intensity to CM peptides decreased when the patients became tolerant. CONCLUSIONS: Our results suggest that the overlap between IgE and IgG4 might be important in natural tolerance acquisition. Further studies are needed to confirm our data and can eventually lead to development of more targeted treatment of food allergy.

Ana o 3-specific IgE is a good predictor for clinically relevant cashew allergy in children.

INTRODUCTION: Component-resolved diagnostics using specific IgE to 2 S albumins has shown to be a valuable new option in diagnostic procedure. Ana o 3 is a 2 S albumin from cashew. The aim of this study was to investigate the role of Ana o 3-specific serum IgE in the diagnosis of cashew allergy and to identify cut-off levels to replace oral food challenges. Moreover, the value of additional determination of total IgE has been investigated. METHODS: In a multicentre study, we analysed specific IgE to cashew extract and Ana o 3 as well as total IgE in children with suspected cashew allergy using the ImmunoCAP-FEIA and a standardized diagnostic procedure including oral challenges where indicated. RESULTS: A total of 61 patients were included in the study. Forty-two were allergic to cashew, and 19 were tolerant. In receiver operating curves, Ana o 3 discriminates between allergic and tolerant children better than cashew-specific IgE with an area under the curve of 0.94 vs 0.78. The ratio of Ana o 3-specific IgE to total IgE did not further improve the diagnostic procedure. Probability curves for Ana o 3-specific IgE have been calculated, and a 95% probability could be estimated at 2.0 kU/l. CONCLUSION: Specific IgE to Ana o 3 is a valuable tool for the diagnosis of cashew allergy. Considering its positive predictive value, it might allow to make a considerable number of oral challenges superfluous.

A new framework for the documentation and interpretation of oral food challenges in population-based and clinical research.

BACKGROUND: The conduct of oral food challenges as the preferred diagnostic standard for food allergy (FA) was harmonized over the last years. However, documentation and interpretation of challenge results, particularly in research settings, are not sufficiently standardized to allow valid comparisons between studies. Our aim was to develop a diagnostic toolbox to capture and report clinical observations in double-blind placebo-controlled food challenges (DBPCFC). METHODS: A group of experienced allergists, paediatricians, dieticians, epidemiologists and data managers developed generic case report forms and standard operating procedures for DBPCFCs and piloted them in three clinical centres. The follow-up of the EuroPrevall/iFAAM birth cohort and other iFAAM work packages applied these methods. RECOMMENDATIONS: A set of newly developed questionnaire or interview items capture the history of FA. Together with sensitization status, this forms the basis for the decision to perform a DBPCFC, following a standardized decision algorithm. A generic form including details about severity and timing captures signs and symptoms observed during or after the procedures. In contrast to the commonly used dichotomous outcome FA vs no FA, the allergy status is interpreted in multiple categories to reflect the complexity of clinical decision-making. CONCLUSION: The proposed toolbox sets a standard for improved documentation and harmonized interpretation of DBPCFCs. By a detailed documentation and common terminology for communicating outcomes, these tools hope to reduce the influence of subjective judgment of supervising physicians. All forms are publicly available for further evolution and free use in clinical and research settings.

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.

Incidence and natural history of hen's egg allergy in the first 2 years of life-the EuroPrevall birth cohort study.

BACKGROUND: Parents and health staff perceive hen's egg allergy (HEA) as a common food allergy in early childhood, but the true incidence is unclear because population-based studies with gold-standard diagnostic criteria are lacking. OBJECTIVE: To establish the incidence and course of challenge-confirmed HEA in children, from birth until the age of 24 months, in different European regions. METHODS: In the EuroPrevall birth cohort study, children with a suspected HEA and their age-matched controls were evaluated in 9 countries, using a standardized protocol including measurement of HE-specific immunoglobulin E-antibodies in serum, skin prick tests, and double-blind, placebo-controlled food challenges (DBPCFC). RESULTS: Across Europe, 12 049 newborns were enrolled, and 9336 (77.5%) were followed up to 2 years of age. In 298 children, HEA was suspected and DBPCFC was offered. HEA by age two was confirmed in 86 of 172 challenged children (mean raw incidence 0.84%, 95% confidence interval (95% CI) 0.67-1.03). Adjusted mean incidence of HEA was 1.23% (95% CI 0.98-1.51) considering possible cases among eligible children who were not challenged. Centre-specific incidence ranged from United Kingdom (2.18%, 95% CI 1.27-3.47) to Greece (0.07%). Half of the HE-allergic children became tolerant to HE within 1 year after the initial diagnosis. CONCLUSIONS: The largest multinational European birth cohort study on food allergy with gold-standard diagnostic methods showed that the mean adjusted incidence of HEA was considerably lower than previously documented, although differences in incidence rates among countries were noted. Half of the children with documented HEA gained tolerance within 1 year postdiagnosis.

Can we identify patients at risk of life-threatening allergic reactions to food?

Anaphylaxis has been defined as a 'severe, life-threatening generalized or systemic hypersensitivity reaction'. However, data indicate that the vast majority of food-triggered anaphylactic reactions are not life-threatening. Nonetheless, severe life-threatening reactions do occur and are unpredictable. We discuss the concepts surrounding perceptions of severe, life-threatening allergic reactions to food by different stakeholders, with particular reference to the inclusion of clinical severity as a factor in allergy and allergen risk management. We review the evidence regarding factors that might be used to identify those at most risk of severe allergic reactions to food, and the consequences of misinformation in this regard. For example, a significant proportion of food-allergic children also have asthma, yet almost none will experience a fatal food-allergic reaction; asthma is not, in itself, a strong predictor for fatal anaphylaxis. The relationship between dose of allergen exposure and symptom severity is unclear. While dose appears to be a risk factor in at least a subgroup of patients, studies report that individuals with prior anaphylaxis do not have a lower eliciting dose than those reporting previous mild reactions. It is therefore important to consider severity and sensitivity as separate factors, as a highly sensitive individual will not necessarily experience severe symptoms during an allergic reaction. We identify the knowledge gaps that need to be addressed to improve our ability to better identify those most at risk of severe food-induced allergic reactions.