The 2021 Dutch Working Party on Antibiotic Policy (SWAB) guidelines for empirical antibacterial therapy of sepsis in adults.

BACKGROUND: The Dutch Working Party on Antibiotic Policy (SWAB) in collaboration with relevant professional societies, has updated their evidence-based guidelines on empiric antibacterial therapy of sepsis in adults. METHODS: Our multidisciplinary guideline committee generated ten population, intervention, comparison, and outcome (PICO) questions relevant for adult patients with sepsis. For each question, a literature search was performed to obtain the best available evidence and assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. The quality of evidence for clinically relevant outcomes was graded from high to very low. In structured consensus meetings, the committee formulated recommendations as strong or weak. When evidence could not be obtained, recommendations were provided based on expert opinion and experience (good practice statements). RESULTS: Fifty-five recommendations on the antibacterial therapy of sepsis were generated. Recommendations on empiric antibacterial therapy choices were differentiated for sepsis according to the source of infection, the potential causative pathogen and its resistance pattern. One important revision was the distinction between low, increased and high risk of infection with Enterobacterales resistant to third generation cephalosporins (3GRC-E) to guide the choice of empirical therapy. Other new topics included empirical antibacterial therapy in patients with a reported penicillin allergy and the role of pharmacokinetics and pharmacodynamics to guide dosing in sepsis. We also established recommendations on timing and duration of antibacterial treatment. CONCLUSIONS: Our multidisciplinary committee formulated evidence-based recommendations for the empiric antibacterial therapy of adults with sepsis in The Netherlands.

[Idiopathic mast cell activation syndrome]. / Het idiopathisch mestcelactivatiesyndroom.

BACKGROUND: Idiopathic mast cell activation syndrome (MCAS) is one of the causes for recurrent complaints. The diagnosis is sometimes delayed but also often made incorrectly. CASE: Our patient presented with recurrent attacks of itching, redness of the skin, diarrhea and near collapse. During an attack his serum tryptase level rose significantly. We could not identify an underlying trigger. A diagnosis of idiopathic mast cell activation syndrome was made. He was successfully treated with a combination of H1 and H2 blockade. CONCLUSION: MCAS is characterized by recurrent complaints. To make the diagnosis a significant rise in mast cell mediators is required. Given the diversity of symptoms many patients with somatically unexplained symptoms wrongfully believe to be suffering from MCAS.

Next-generation Allergic Rhinitis and Its Impact on Asthma (ARIA) guidelines for allergic rhinitis based on Grading of Recommendations Assessment, Development and Evaluation (GRADE) and real-world evidence

The selection of pharmacotherapy for patients with allergic rhinitis aims to control the disease and depends on many factors. Grading of Recommendations Assessment, Development and Evaluation (GRADE) guidelines have considerably improved the treatment of allergic rhinitis. However, there is an increasing trend toward use of real-world evidence to inform clinical practice, especially because randomized controlled trials are often limited with regard to the applicability of results. The Contre les Maladies Chroniques pour un Vieillissement Actif (MACVIA) algorithm has proposed an allergic rhinitis treatment by a consensus group. This simple algorithm can be used to step up or step down allergic rhinitis treatment. Next-generation guidelines for the pharmacologic treatment of allergic rhinitis were developed by using existing GRADE-based guidelines for the disease, real-world evidence provided by mobile technology, and additive studies (allergen chamber studies) to refine the MACVIA algorithm.

Next-generation Allergic Rhinitis and Its Impact on Asthma (ARIA) guidelines for allergic rhinitis based on Grading of Recommendations Assessment, Development and Evaluation (GRADE) and real-world evidence.

The selection of pharmacotherapy for patients with allergic rhinitis aims to control the disease and depends on many factors. Grading of Recommendations Assessment, Development and Evaluation (GRADE) guidelines have considerably improved the treatment of allergic rhinitis. However, there is an increasing trend toward use of real-world evidence to inform clinical practice, especially because randomized controlled trials are often limited with regard to the applicability of results. The Contre les Maladies Chroniques pour un Vieillissement Actif (MACVIA) algorithm has proposed an allergic rhinitis treatment by a consensus group. This simple algorithm can be used to step up or step down allergic rhinitis treatment. Next-generation guidelines for the pharmacologic treatment of allergic rhinitis were developed by using existing GRADE-based guidelines for the disease, real-world evidence provided by mobile technology, and additive studies (allergen chamber studies) to refine the MACVIA algorithm.

Parental and child factors associated with inhalant and food allergy in a population-based prospective cohort study: the Generation R Study.

The prevalence of allergic diseases in children is markedly increasing to epidemic proportions. The aim of this study is to describe the presence and examine associated parental and child characteristics of allergic sensitization and physician-diagnosed allergy in Dutch children at age 10 years. This study among 5471 children was performed in a population-based prospective cohort from fetal life onwards. Allergic sensitization was measured by skin prick tests. Physician-diagnosed allergy and parental and child characteristics were collected by questionnaires. In children aged 10 years, inhalant and food allergic sensitization was present in 32.2% and 7.1%, and physician-diagnosed inhalant and food allergy in 12.4% and 2.3%. Maternal and paternal history of allergy, eczema or asthma was associated with increased risks of physician-diagnosed inhalant allergy (aOR (95% CI) 1.44 (1.23-1.70) and 1.59 (1.30-1.94), respectively), but not with food allergy. Asthma and eczema ever at age 10 years were associated with increased risks of physician-diagnosed inhalant allergy (4.60 (3.55-5.96) and 2.42 (1.94-3.03), respectively). Eczema ever at age 10 years was associated with an increased risk of physician-diagnosed food allergy (5.78, 3.04-9.52), with the highest risk of cashew (7.36, 3.20-16.94) and peanut (5.58, 3.08-10.10) food allergy.Conclusions: We found strong effects of parental history of allergy, eczema or asthma on the presence of physician-diagnosed inhalant allergy in children at age 10 years. Eczema ever at age 10 years was a strong risk factor for the development of physician-diagnosed inhalant and food allergy. What is Known: • The prevalence of allergic diseases in children has markedly increased. • Early-life influences are critically important in the development of allergic diseases. What is New: • Maternal and paternal history of allergy, eczema or asthma is associated with increased risks of physician-diagnosed inhalant allergy but not with food allergy. • Eczema ever at age 10 years is associated with an increased risk of physician-diagnosed food allergy, with the highest risk for cashew and peanut food allergy.

EAACI Guidelines on Allergen Immunotherapy: House dust mite-driven allergic asthma.

Allergen immunotherapy (AIT) has been in use for the treatment of allergic disease for more than 100 years. Asthma treatment relies mainly on corticosteroids and other controllers recommended to achieve and maintain asthma control, prevent exacerbations, and improve quality of life. AIT is underused in asthma, both in children and in adults. Notably, patients with allergic asthma not adequately controlled on pharmacotherapy (including biologics) represent an unmet health need. The European Academy of Allergy and Clinical Immunology has developed a clinical practice guideline providing evidence-based recommendations for the use of house dust mites (HDM) AIT as add-on treatment for HDM-driven allergic asthma. This guideline was developed by a multi-disciplinary working group using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. HDM AIT was separately evaluated by route of administration and children and adults: subcutaneous (SCIT) and sublingual AIT (SLIT), drops, and tablets. Recommendations were formulated for each. The important prerequisites for successful treatment with HDM AIT are (a) selection of patients most likely to respond to AIT and (b) use of allergen extracts and desensitization protocols of proven efficacy. To date, only AIT with HDM SLIT-tablet has demonstrated a robust effect in adults for critical end points (exacerbations, asthma control, and safety). Thus, it is recommended as an add-on to regular asthma therapy for adults with controlled or partially controlled HDM-driven allergic asthma (conditional recommendation, moderate-quality evidence). HDM SCIT is recommended for adults and children, and SLIT drops are recommended for children with controlled HDM-driven allergic asthma as the add-on to regular asthma therapy to decrease symptoms and medication needs (conditional recommendation, low-quality evidence).

A reintroduction of environmental mite allergen control strategies for asthma treatment and the debate on their effectiveness.

Asthma affects three hundred million people worldwide. The effectiveness of house dust mite allergen control for asthma treatment is debatable. One aspect that has been little discussed in existing meta-analyses is the possible role of environmental strategies. Here, we reintroduce the previously defined strategies for mite allergen control and discuss their importance to the debate on clinical effectiveness. The strategy of concurrent bedroom interventions is related to the combined use of a priori defined interventions, while the strategy of exposure-based control relates to the treatment of relevant textiles after assessing exposure. The air purification strategy aims to purify the human breathing zone of airborne allergens. In Western European patient practice, the use of these strategies differs. A post hoc study of the dominant Cochrane review by Gøtzsche and Johansen (Cochrane Database of Systematic Reviews, 2008, Art. No: CD001187) appears to indicate that a majority of the underlying trials reported on the strategy of concurrent bedroom interventions, which were mainly executed in a minimal manner. Some trials have reported on the air purification strategy and may potentially alter the debate on effectiveness. No trial has reported on the strategy of exposure-based control. We therefore hypothesize that the absence of evidence for the effectiveness of mite allergen control for asthma treatment applies to the strategy of concurrent bedroom interventions. The evidence-based effectiveness of the exposure-based control strategy appears to be undetermined. The results of our post hoc reanalysis urge that future meta-analyses of mite allergen control should a priori define the environmental strategy under study. Future trials of mite allergen control are warranted to test the exposure-based strategy as well as the sparsely tested strategy of air purification.

Erratum to: Allergen immunotherapy for allergic asthma: protocol for a systematic review.

[This corrects the article DOI: 10.1186/s13601-016-0094-y.].

Allergen immunotherapy for allergic rhinoconjunctivitis: a systematic overview of systematic reviews.

BACKGROUND: The European Academy of Allergy and Clinical Immunology (EAACI) is developing Guidelines on Allergen Immunotherapy (AIT) for Allergic Rhinoconjunctivitis (ARC). To inform the development of recommendations, we sought to critically assess the systematic review evidence on the effectiveness, safety and cost-effectiveness of AIT for ARC. METHODS: We undertook a systematic overview, which involved searching nine international biomedical databases from inception to October 31, 2015. Studies were independently screened by two reviewers against pre-defined eligibility criteria and critically appraised using the Critical Appraisal Skills Programme (CASP) Systematic Review Checklist for systematic reviews. Data were descriptively synthesized. RESULTS: Our searches yielded a total of 5932 potentially eligible studies, from which 17 systematic reviews met our inclusion criteria. Eight of these were judged to be of high, five moderate and three low quality. These reviews suggested that, in carefully selected patients, subcutaneous (SCIT) and sublingual (SLIT) immunotherapy resulted in significant reductions in symptom scores and medication requirements. Serious adverse outcomes were rare for both SCIT and SLIT. Two systematic reviews reported some evidence of potential cost savings associated with use of SCIT and SLIT. CONCLUSIONS: We found moderate-to-strong evidence that SCIT and SLIT can, in appropriately selected patients, reduce symptoms and medication requirements in patients with ARC with reassuring safety data. This evidence does however need to be interpreted with caution, particularly given the heterogeneity in the populations, allergens and protocols studied. There is a lack of data on the relative effectiveness, cost-effectiveness and safety of SCIT and SLIT. We are now systematically reviewing all the primary studies, including recent evidence that has not been incorporated into the published systematic reviews.

Allergen immunotherapy for allergic asthma: 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 Allergic Asthma. We seek to critically assess the effectiveness, cost-effectiveness and safety of AIT in the management of allergic asthma. 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 synthesised. DISCUSSION: The findings from this review will be used to inform the development of recommendations for EAACI's Guidelines on AIT.

[Diagnostic evaluation of ß-lactam antibiotic allergy]. / Diagnostiek van betalactamantibiotica-allergie.

Many patients report a ß-lactam allergy or hypersensitivity without actually having this allergy. Targeted questioning, in combination with an accurate description of the nature of the symptoms, leads to rejection of a large number of these presumed allergies. In a suspected allergic reaction one has to distinguish between the potentially life-threatening, acute type I mediated allergy and delayed type IV skin reaction. The diagnostic evaluation of a suspected allergy is described in this article. Three cases are presented of a presumed allergic reaction to ß-lactam antibiotics. Patient A was a 62-year-old woman with anaphylaxis triggered by amoxicillin/clavulanate who, after analysis, was advised to avoid all ß-lactam antibiotics. Patient B was a 58-year-old man with anaphylaxis triggered by amoxicillin/clavulanate as a result of a selective allergy to amoxicillin. Patient C was a 50-year-old man who had had a possible reaction to a penicillin in his childhood. Analysis in an allergology department can be useful for further treatment.

Sublingual immunotherapy: World Allergy Organization position paper 2013 update.

We have prepared this document, "Sublingual Immunotherapy: World Allergy Organization Position Paper 2013 Update", according to the evidence-based criteria, revising and updating chapters of the originally published paper, "Sublingual Immunotherapy: World Allergy Organization Position Paper 2009", available at http://www.waojournal.org. Namely, these comprise: "Mechanisms of sublingual immunotherapy;" "Clinical efficacy of sublingual immunotherapy" - reporting all the data of all controlled trials published after 2009; "Safety of sublingual immunotherapy" - with the recently published Grading System for adverse reactions; "Impact of sublingual immunotherapy on the natural history of respiratory allergy" - with the relevant evidences published since 2009; "Efficacy of SLIT in children" - with detailed analysis of all the studies; "Definition of SLIT patient selection" - reporting the criteria for eligibility to sublingual immunotherapy; "The future of immunotherapy in the community care setting"; "Methodology of clinical trials according to the current scientific and regulatory standards"; and "Guideline development: from evidence-based medicine to patients' views" - including the evolution of the methods to make clinical recommendations.Additionally, we have added new chapters to cover a few emerging crucial topics: "Practical aspects of schedules and dosages and counseling for adherence" - which is crucial in clinical practice for all treatments; "Perspectives and new approaches" - including recombinant allergens, adjuvants, modified allergens, and the concept of validity of the single products. Furthermore, "Raising public awareness about sublingual immunotherapy", as a need for our patients, and strategies to increase awareness of allergen immunotherapy (AIT) among patients, the medical community, all healthcare stakeholders, and public opinion, are also reported in detail.

Sensitisation patterns and association with age, gender, and clinical symptoms in children with allergic rhinitis in primary care: a cross-sectional study.

BACKGROUND: Polysensitisation is a frequent phenomenon in patients with allergic rhinitis. However, few studies have investigated the characteristics of polysensitised children, especially in primary care. OBJECTIVES: This analysis describes the patterns of sensitisation to common allergens and the association with age, gender, and clinical symptoms in children in primary care diagnosed with allergic rhinitis. METHODS: Cross-sectional data from two randomised double-blind placebo-controlled studies were used to select children aged 6-18 years (n=784) with a doctor's diagnosis of allergic rhinitis or use of relevant medication for allergic rhinitis in primary care. They were assessed for age, gender, specific IgE (type and number of sensitisations), nasal and eye symptom scores. RESULTS: In 699 of the 784 children (89%) with a doctor's diagnosis or relevant medication use, a positive IgE test for one or more allergens was found. Polysensitisation (>2 sensitisations) was found in 69% of all children. Sensitisation was more common in children aged 9-13 than in younger children aged 5-8 years (p=0.03). Monosensitisation and polysensitisation were not significantly different in girls and boys. The severity of clinical symptoms did not differ between polysensitised and monosensitised children, but symptoms were significantly lower in non-sensitised children. CONCLUSIONS: Polysensitisation to multiple allergens occurs frequently in children with allergic rhinitis in general practice. Overall, clinical symptoms are equally severe in polysensitised and monosensitised children. Treatment decisions for allergic rhinitis should be made on the basis of a clinical history and allergy testing.

[Research into sensitization and allergies to latex: results after 10 years of the use of powder-free latex gloves]. / Sensibilisatie en allergie voor natuurrubberlatex: onderzoeksresultaten 10 jaar na introductie van een latexprotocol.

OBJECTIVE: To compare the prevalence of sensitization and allergy to natural rubber latex amongst Erasmus Medical Centre (MC) operating theatre employees before and 10 years after the introduction of powder-free latex gloves. DESIGN: Descriptive study. METHOD: Employees working permanently in the operating theatre were evaluated in 1998 (n = 163) and in 2009 (n = 178) for sensitization and allergies to natural latex by means of questionnaires, serological analyses and skin testing. The prevalence of sensitization and allergies within these 2 groups was then established and compared. RESULTS: The two groups were comparable in terms of gender, smoking habits, job classification, work-related symptoms and the number of individuals who had atopy. In 2009, the prevalence of sensitization to latex was statistically significantly lower than in 1998 (4.5 vs. 14.1%). Allergy to latex was also established a statistically significantly fewer number of times in 2009 than in 1998 (2.8 vs. 9.8%). This same trend could be observed in the subgroup that participated both years (n = 49). Individuals with an atopic constitution had a statistically significant higher risk of developing hypersensitivity to natural latex; the risk of developing an allergy to latex was also higher, but not significantly. CONCLUSION: After the study in 1998, the introduction of sterile, powder-free latex gloves very likely led to a decline in the prevalence of sensitization and allergy to natural latex in 2009.

Exhaled nitric oxide measures allergy not symptoms in children with allergic rhinitis in primary care: a prospective cross-sectional and longitudinal cohort study.

BACKGROUND: Allergic rhinitis (AR) and asthma are both inflammatory diseases and are often associated. Relationships between fractional exhaled nitric oxide (FeNO) and asthma, atopy, and quality of life have been shown. AIMS: This study aimed to determine whether FeNO in children with AR (n=158) or combined AR and asthma (n=93) was associated with clinical symptoms, house dust mite (HDM)-specific IgE, and rhinitis-specific quality of life, both cross-sectionally and longitudinally. METHODS: Children with AR aged 6-18 years (n=251) in primary care were assessed for FeNO, nasal symptom scores, asthma symptom scores, quality of life, and HDM-specific IgE at baseline and 2 years later. RESULTS: We found similarly elevated FeNO in children with only AR and in those with combined AR and asthma. No correlations were found between FeNO and nasal or asthma symptoms and rhinitis-related quality of life. Longitudinal correlations were strongest for HDM-specific IgE (r=0.91, p<0.0001). CONCLUSIONS: FeNO was similar in a selected group of children with AR with and without asthma in primary care and was unrelated to symptoms or quality of life in both groups. FeNO is unlikely to be a useful biomarker of the clinical severity of upper or lower airway disease in primary care.