Vaccine effectiveness against COVID-19 related hospital admission in the Netherlands by medical risk condition: A test-negative case-control study.

INTRODUCTION: Vaccination remains crucial in reducing COVID-19 hospitalizations and mitigating the strain on healthcare systems. We conducted a multicenter study to assess vaccine effectiveness (VE) of primary and booster vaccination against hospitalization and to identify subgroups with reduced VE. METHODS: From March to July 2021 and October 2021 to January 2022, a test-negative case-control study was conducted in nine Dutch hospitals. The study included adults eligible for COVID-19 vaccination who were hospitalized with respiratory symptoms. Cases tested positive for SARS-CoV-2 within 14 days prior to or 48 h after admission, while controls tested negative. Logistic regression was used to calculate VE, adjusting for calendar week, sex, age, nursing home residency and comorbidity. We explored COVID-19 case characteristics and whether there are subgroups with less effective protection by vaccination against COVID-19 hospitalization. RESULTS: Between October 2021 to January 2022, when the Delta variant was dominant, 335 cases and 277 controls were included. VE of primary and booster vaccination was 78 % (95 % CI: 65-86), and 89 % (95 % CI: 69-96), respectively. Using data from both study periods, including 700 cases and 511 controls, VE of primary vaccination was significantly reduced in those aged 60+ and patients with malignancy, chronic cardiac disease or an immunocompromising condition. CONCLUSION: Although VE against hospitalization was 78% and increased to 89% after boosting during the Delta-dominant study period, VE was lower in certain high risk groups, for which indirect protection or other protective measures might be of added importance.

Vaccine effectiveness against COVID-19 related hospital admission in the Netherlands: A test-negative case-control study.

INTRODUCTION: Real-world vaccine effectiveness (VE) estimates are essential to identify potential groups at higher risk of break-through infections and to guide policy. We assessed the VE of COVID-19 vaccination against COVID-19 hospitalization, while adjusting and stratifying for patient characteristics. METHODS: We performed a test-negative case-control study in six Dutch hospitals. The study population consisted of adults eligible for COVID-19 vaccination hospitalized between May 1 and June 28, 2021 with respiratory symptoms. Cases were defined as patients who tested positive for SARS-CoV-2 by PCR during the first 48 h of admission or within 14 days prior to hospital admission. Controls were patients tested negative at admission and did not have a positive test during the 2 weeks prior to hospitalization. VE was calculated using multivariable logistic regression, adjusting for calendar week, sex, age, comorbidity and nursing home residency. Subgroup analysis was performed for age, sex and different comorbidities. Secondary endpoints were ICU-admission and mortality. RESULTS: 379 cases and 255 controls were included of whom 157 (18%) were vaccinated prior to admission. Five cases (1%) and 40 controls (16%) were fully vaccinated (VE: 93%; 95% CI: 81 - 98), and 40 cases (11%) and 70 controls (27%) were partially vaccinated (VE: 70%; 95% CI: 50-82). A strongly protective effect of vaccination was found in all comorbidity subgroups. No ICU-admission or mortality were reported among fully vaccinated cases. Of unvaccinated cases, mortality was 10% and 19% was admitted at the ICU. CONCLUSION: COVID-19 vaccination provides a strong protective effect against COVID-19 related hospital admission, in patients with and without comorbidity.

Examining the Distribution and Impact of Single-Nucleotide Polymorphisms in the Capsular Locus of Streptococcus pneumoniae Serotype 19A.

Streptococcus pneumoniae serotype 19A prevalence has increased after the implementation of the PCV7 and PCV10 vaccines. In this study, we have provided, with high accuracy, the genetic diversity of the 19A serotype in a cohort of Dutch invasive pneumococcal disease patients and asymptomatic carriers obtained in the period from 2004 to 2016. The whole genomes of the 338 pneumococcal isolates in this cohort were sequenced and their capsule (cps) loci compared to examine their diversity and determine the impact on the production of capsular polysaccharide (CPS) sugar precursors and CPS shedding. We discovered 79 types with a unique cps locus sequence. Most variation was observed in the rmlB and rmlD genes of the TDP-Rha synthesis pathway and in the wzg gene, which is of unknown function. Interestingly, gene variation in the cps locus was conserved in multiple alleles. Using RmlB and RmlD protein models, we predict that enzymatic function is not affected by the single-nucleotide polymorphisms as identified. To determine if RmlB and RmlD function was affected, we analyzed nucleotide sugar levels using ultrahigh-performance liquid chromatography-mass spectrometry (UHPLC-MS). CPS precursors differed between 19A cps locus subtypes, including TDP-Rha, but no clear correlation was observed. Also, significant differences in multiple nucleotide sugar levels were observed between phylogenetically branched groups. Because of indications of a role for Wzg in capsule shedding, we analyzed if this was affected. No clear indication of a direct role in shedding was found. We thus describe genotypic variety in rmlB, rmlD, and wzg in serotype 19A in the Netherlands, for which we have not discovered an associated phenotype.

Impact and effectiveness of the 10-valent pneumococcal conjugate vaccine on invasive pneumococcal disease among children under 5 years of age in the Netherlands.

BACKGROUND: In 2011, the 7-valent pneumococcal conjugate vaccine (PCV7) was replaced by the 10-valent vaccine (PCV10) in the Netherlands. We report on impact and effectiveness against invasive pneumococcal disease (IPD) in children aged under 5 years by switching from PCV7 to PCV10. METHOD: We included IPD cases between 2004 and 2019 in children aged < 5 years reported via the national surveillance system. To assess the impact of the PCV10 vaccination program we compared IPD incidence 6-8 years after PCV10 introduction (2017-2019) to the two years just before the switch to PCV10 (2009-2011). We estimated vaccine effectiveness (VE) using the indirect cohort method, comparing vaccination status (at least two vaccine doses) in IPD-cases caused by PCV10 serotypes (cases) to non-PCV10 IPD cases (controls), in children eligible for PCV10. RESULTS: The overall incidence decreased from 8.7 (n = 162) in 2009-2011 to 7.3 per 100.000 (n = 127) in 2017-2019 (Incidence rate ratio (IRR) 0.83, 95%CI: 0.66; 1.05). IPD caused by the additional serotypes included in PCV10 declined by 93% (IRR 0.07, 95%CI: 0.02; 0.23). Incidence of non-PCV10 IPD showed a non-significant increase (IRR 1.25, 95%CI: 0.96; 1.63). Among 231 IPD-cases eligible for PCV10, the overall VE was 91% (95%CI: 67; 97) and did not differ by sex or age at diagnosis. Effectiveness against non-PCV10 serotype 19A IPD was non-significant with an estimate of 28% (95%CI:-179; 81). CONCLUSION: PCV10 is highly effective in protecting against IPD in Dutch children under 5 years with limited serotype replacement after switching from PCV7 to PCV10. We found no evidence for significant cross-protection of PCV10 against 19A serotype IPD.

Predicted coverage by 4CMenB vaccine against invasive meningococcal disease cases in the Netherlands.

Neisseria meningitidis serogroup B is a major cause of invasive meningococcal disease in Europe. In the absence of a conjugate serogroup B vaccine, a subcapsular 4CMenB vaccine was developed. Data on 4CMenB vaccine efficacy is still limited. Recently, genomic MATS (Meningococcal Antigen Typing System) was developed as a tool to predict strain coverage, using vaccine antigens sequence data. We characterized all invasive meningococcal isolates received by the Netherlands Reference Laboratory for Bacterial Meningitis (NRLBM) in two epidemiological years 2017-2019 using whole-genome sequencing and determined serogroup, clonal complex (cc) and estimated 4CMenB vaccine coverage by gMATS. Of 396 cases of invasive meningococcal disease, corresponding to an incidence of 1.22 cases/105 inhabitants, 180 (45%) were serogroup W, 155 (39%) serogroup B, 46 (12%) serogroup Y, 10 (3%) serogroup C, 2 non-groupable (0.5%) and 3 (0.7%) unknown. The incidence was the highest among 0-4 years olds (4 cases/105 inhabitants), and 57/72 (79%) of these cases were serogroup B. Serogroup W predominated among persons 45 years of age or older with 110/187 (59%) cases. Serogroup B isolates comprised 11 different clonal complexes, with 103/122 (84%) isolates belonging to 4 clonal complexes: cc32, cc41/44, cc269 and cc213. In contrast, serogroup W isolates were genetically similar with 95% belonging to cc11. Of 122 serogroup B isolates, 89 (73%; 95% CI: 64-80%) were estimated to be covered by 4CMenB and the degree of coverage varied largely by clonal complex and age. Among the 0-4 year olds, 25 of 43 (58%; 95% CI: 43-72%) MenB isolates were estimated to be covered. Since the coverage of the 4CMenB vaccine is dependent on circulating clonal complexes, our findings emphasize the need for surveillance of circulating meningococcal strains. In addition, estimation of age specific coverage is relevant to determine the right target age group for vaccination.

Measuring vaccine effectiveness against persistent HPV infections: a comparison of different statistical approaches.

BACKGROUND: Persistent high-risk human papillomavirus (HPV) infection is endorsed by the World Health Organization as an intermediate endpoint for evaluating HPV vaccine effectiveness/efficacy. There are different approaches to estimate the vaccine effectiveness/efficacy against persistent HPV infections. METHODS: We performed a systematic literature search in Pubmed to identify statistical approaches that have been used to estimate the vaccine effectiveness/efficacy against persistent HPV infections. We applied these methods to data of a longitudinal observational study to assess their performance and compare the obtained vaccine effectiveness (VE) estimates. RESULTS: Our literature search identified four approaches: the conditional exact test for comparing two independent Poisson rates using a binomial distribution, Generalized Estimating Equations for Poisson regression, Prentice Williams and Peterson total time (PWP-TT) and Cox proportional hazards regression. These approaches differ regarding underlying assumptions and provide different effect measures. However, they provided similar effectiveness estimates against HPV16/18 and HPV31/33/45 persistent infections in a cohort of young women eligible for routine HPV vaccination (range VE 93.7-95.1% and 60.4-67.7%, respectively) and seemed robust to violations of underlying assumptions. CONCLUSIONS: As the rate of subsequent infections increased in our observational cohort, we recommend PWP-TT as the optimal approach to estimate the vaccine effectiveness against persistent HPV infections in young women. Confirmation of our findings should be undertaken by applying these methods after longer follow-up in our study, as well as in different populations.

Comparison of antibody response between boys and girls after infant and childhood vaccinations in the Netherlands.

BACKGROUND: Infectious diseases can differ by sex in their incidence, prevalence, or severity of disease. These differences may be induced by sex-dependent immune responses and resulting protection, for example after vaccination. Therefore, this study aims to assess possible sex-differences in immunoglobulin levels (IgG) after infant and childhood vaccination. METHODS: Data from a national cross-sectional serosurvey conducted in 2006/2007 were used (Pienter 2). We compared IgG levels against measles, mumps, rubella, diphtheria, tetanus, poliomyelitis, pertussis, Haemophilus influenzae type b (Hib), and Neisseria meningitidis serogroup C (MenC) between girls and boys both short term (1 month to 1 year) and long term (1-3 year) after infant and childhood vaccinations, using linear regression analysis. Proportions of boys and girls reaching a protective IgG level were compared using Fishers exact test. RESULTS: Differences in IgG were found at specific time points after vaccination against measles, mumps, rubella, MenC, and polio. The geometric mean concentration or titer (GMC/T) girls:boys ratios ranged between 1.10 for polio type 1 <1 year after the first childhood booster to 1.90 for MenC <1 year after infant vaccination, indicating higher antibody levels in girls. No significant differences were found between boys and girls for diphtheria, tetanus, pertussis, and Hib at either time point. Proportions with protective levels differed only at 1-3 years after infant vaccination for mumps (82.5% boys vs. 91.9% girls, p = 0.046), and at the same time point for MenC (7.0% boys vs. 18.2% girls, p = 0.015), and polio type 1 (87.8% boys vs. 95.9% girls, p = 0.047). CONCLUSION: Differences in IgG between boys and girls were generally small and not consistent, neither between pathogens nor within pathogens. If differences were observed, girls were favored over boys. On the whole, the results suggest that there are no major sex differences in protection from the studied pathogens in the Netherlands.

Effect of latent cytomegalovirus infection on the antibody response to influenza vaccination: a systematic review and meta-analysis.

Latent infection with cytomegalovirus (CMV) is thought to accelerate aging of the immune system. With age, influenza vaccine responses are impaired. Although several studies investigated the effect of CMV infection on antibody responses to influenza vaccination, this led to contradicting conclusions. Therefore, we investigated the relation between CMV infection and the antibody response to influenza vaccination by performing a systematic review and meta-analysis. All studies on the antibody response to influenza vaccination in association with CMV infection were included (n = 17). The following outcome variables were extracted: (a) the geometric mean titer pre-/post-vaccination ratio (GMR) per CMV serostatus group, and in addition (b) the percentage of subjects with a response per CMV serostatus group and (c) the association between influenza- and CMV-specific antibody titers. The influenza-specific GMR revealed no clear evidence for an effect of CMV seropositivity on the influenza vaccine response in young or old individuals. Meta-analysis of the response rate to influenza vaccination showed a non-significant trend towards a negative effect of CMV seropositivity. However, funnel plot analysis suggests that this is a consequence of publication bias. A weak negative association between CMV antibody titers and influenza antibody titers was reported in several studies, but associations could not be analyzed systematically due to the variety of outcome variables. In conclusion, by systematically integrating the available studies, we show that there is no unequivocal evidence that latent CMV infection affects the influenza antibody response to vaccination. Further studies, including the level of CMV antibodies, are required to settle on the potential influence of latent CMV infection on the influenza vaccine response.

Impact of infant pneumococcal conjugate vaccination on community acquired pneumonia hospitalization in all ages in the Netherlands.

BACKGROUND: The long-term impact of pneumococcal conjugate vaccines on pneumonia hospitalizations in all age-groups varies between countries. In the Netherlands, the 7-valent pneumococcal conjugate vaccine (PCV7) was implemented for newborns in 2006 and replaced by PCV10 in 2011. We assessed the impact of PCVs on community-acquired pneumonia (CAP) hospitalization rates in all age-groups. METHODS: A time series analysis using Poisson regression was performed on 155,994 CAP hospitalizations. Hospitalization rates were calculated using the total number of hospitalizations as denominator. The time trend in the pre-PCV period (1999-2006) was extrapolated to predict the hospitalization rate in the post-PCV period (2006-2014) if PCV had not been implemented. Rate ratios over time were calculated by comparing observed and predicted time trends. RESULTS: In children <5 years of age, the observed hospitalization rates during the post-PCV period were significantly lower than predicted if PCV had not been implemented (0-6 months: 0.62, 95% CI: 0.41-0.96; 6 months - 1 year: 0.67, 95% CI: 0.50-0.90; 2-4 years: 0.78, 95% CI: 0.61-0.97). In all other age-groups, rate ratios declined over time but did not reach statistical significance. CONCLUSIONS: After introduction of PCV, CAP hospitalizations declined in young children but no clear impact of PCV on CAP hospitalizations was seen in other age-groups.

[Gastrointestinal symptoms with meningococcal infection. Emergence of Neisseria meningitidis serogroup W.] / Gastro-intestinale klachten bij meningokokkeninfectie.

BACKGROUND: Meningococcal disease usually presents as meningitis and/or septicaemia, but can also present as pneumonia or arthritis. Since 2000, a worldwide increase in meningococcal disease is reported which is caused by a new virulent clone of serogroup W (MenW:cc11). This subtype is more likely to give an atypical clinical presentation and results in high mortality rates. CASE DESCRIPTION: A 68-year-old woman with polymyalgia rheumatica, managed with prednisone, developed an acute gastrointestinal syndrome of nausea, diarrhoea, vomiting, fever and chills. She presented at the Emergency Department and was admitted to intensive care for septic shock. Blood cultures revealed MenW:cc11 infection. She received antibiotic treatment and left the hospital in good condition 8 days after admission. CONCLUSION: MenW:cc11 is associated with gastrointestinal symptoms and sepsis. Recognition of this atypical clinical presentation is important for a timely and adequate treatment and for antibiotic prophylaxis of family members and close contacts.

Comparing vaccines: a systematic review of the use of the non-inferiority margin in vaccine trials.

BACKGROUND: Non-inferiority (NI) randomized controlled trials (RCTs) aim to demonstrate that a new treatment is no worse than a comparator that has already shown its efficacy over placebo within a pre-specified margin. However, clear guidelines on how the NI margin should be determined are lacking for vaccine trials. A difference (seroprevalence/risk) of 10% or a geometric mean titre/concentration (GMT) ratio of 1.5 or 2.0 in antibody levels is implicitly recommended for vaccine trials. We aimed to explore which NI margins were used in vaccine RCTs and how they were determined. METHODS: A systematic search for NI vaccine RCTs yielded 177 eligible articles. Data were extracted from these articles using a standardized form and included general characteristics and characteristics specific for NI trials. Relations between the study characteristics and the NI margin used were explored. RESULTS: Among the 143 studies using an NI margin based on difference (n=136 on immunogenicity, n=2 on efficacy and n=5 on safety), 66% used a margin of 10%, 23% used margins lower than 10% (range 1-7.5%) and 11% used margins larger than 10% (range 11.5-25%). Of the 103 studies using a NI margin based on the GMT ratio, 50% used a margin of 0.67/1.5 and 49% used 0.5/2.0. As observed, 85% of the studies did not discuss the method of margin determination; and 19% of the studies lacked a confidence interval or p-value for non-inferiority. CONCLUSION: Most NI vaccine RCTs used an NI margin of 10% for difference or a GMT ratio of 1.5 or 2.0 without a clear rationale. Most articles presented enough information for the reader to make a judgement about the NI margin used and the conclusions. The reporting on the design, margins used and results of NI vaccine trials could be improved; more explicit guidelines may help to achieve this end.

Treatment of infantile haemangiomas with atenolol: comparison with a historical propranolol group.

Propranolol, a lipophilic non-selective beta-blocker, has proven to be effective in the treatment of infantile haemangioma (IH). However, several side effects have been reported. Atenolol, a hydrophilic selective beta-1 blocker, could be an alternative and associated with fewer side effects. Thirty consecutive patients with IH were treated with atenolol between June 2010 and May 2011. The therapeutic effect was judged by clinical assessment and quantified by using a visual analogue scale (VAS) and the Haemangioma Activity Score (HAS). Side effects were also evaluated. The atenolol cohort was compared with a previously described cohort of 28 patients treated with propranolol between July 2008 and December 2009. Clinical involution was present in 90% (27/30) of the IH patients treated with atenolol. Mild side effects occurred in 40% (12/30) of these patients and severe side effects occurred in 3% (1/30). Compared with the previously described cohort treated with propranolol, mild side effects occurred in 50% (14/28) and severe side effects in 25% (7/28) of the patients (p=0.04). Quantitative improvement of the IH in the atenolol group (n=27) showed no significant difference in either the VAS score or the HAS compared to the propranolol group (n=24). This study indicates that atenolol is effective in the treatment of IH. Compared with a historical control group treated with propranolol, the effects of atenolol seem to be similar and less frequently associated with severe side effects. Randomised clinical trials are necessary to evaluate the efficacy and safety of atenolol treatment in IH.

IgE binding to peanut components by four different techniques: Ara h 2 is the most relevant in peanut allergic children and adults.

BACKGROUND: Several studies have analysed the diagnostic value of specific IgE (sIgE) for individual peanut allergens. However, little is known about the concordance between different techniques available in both children and adults. OBJECTIVE: To evaluate the value of individual peanut allergens by different techniques, i.e. multi-plexed microarray, single-plexed IgE assay, skin prick test (SPT) and immunoblot in both peanut allergic adults and children. METHODS: Sensitization patterns to peanut allergens Ara h 1, 2, 3, and 8 were evaluated using four different techniques: multi-plexed microarray immunoassay, single-plexed IgE assay, SPT and immunoblot. Twenty-two peanut allergic adults and 15 children scored on clinical severity according to double-blind, placebo-controlled food challenges and 27 atopic control patients were included. RESULTS: Comparable sensitivity values were found between all four techniques in adults, with the highest sensitivity for Ara h 2 (76.2-95.5%, compared to 100% with all techniques in children). The multi-plexed assay to Ara h 1 (93.3%) demonstrated a higher sensitivity compared with the other three techniques (P = 0.04) in children, but absolute values were perfectly correlated. There were no differences between adults and children. The area under the receiver operating characteristic curve (AUC) of sIgE to Ara h 1 was higher with the multi-plexed assay compared with the single-plexed assay (0.91 vs. 0.75). In adults, sIgE to Ara h 1, 2, and 3 was correlated with clinical severity. No such correlation was found in children. CONCLUSION AND CLINICAL RELEVANCE: In conclusion, the single- and multi-plexed assay, SPT and immunoblot perform equally in both peanut allergic adults and children, with Ara h 2 being most often recognized with all techniques. Specific IgE to Ara h 1, 2, and 3 in adults was correlated with severity.

Added value of pharmacogenetic testing in predicting statin response: results from the REGRESS trial.

It was investigated whether pharmacogenetic factors, both as single polymorphism and as gene-gene interactions, have an added value over non-genetic factors in predicting statin response. Five common polymorphisms were selected in apolipoprotein E, angiotensin-converting enzyme, hepatic lipase and toll-like receptor 4. Linear regression models were built and compared on R(2) to estimate the added value of single polymorphisms and gene-gene interactions. The selected polymorphisms and the gene-gene interactions had a small added value in predicting change in low-density lipoprotein cholesterol levels (LDL-c) as response to statins over the non-genetic predictors (P=0.104), and also in predicting LDL-c in non-treated patients (P=0.016). Moreover, four gene-gene interactions with statin therapy were identified. The added value of genetic factors over non-genetic variables is for the greater part produced by gene-gene interactions. This underlines the importance to examine gene-gene interactions in future (pharmaco)genetic research.

Safety learning from drugs of the same class: room for improvement.

This study was aimed at assessing the extent of safety learning from data pertaining to other drugs of the same class. We studied drug classes for which the first and second drugs were centrally registered in the European Union from 1995 to 2008. We assessed whether adverse drug reactions (ADRs) associated with one of the drugs also appeared in the Summary of Product Characteristics (SPC) of the other drug, either initially or during the postmarketing phase. We identified 977 ADRs from 19 drug pairs, of which 393 ADRs (40.2%) were listed in the SPCs of both drugs of a pair. Of these 393 that were present in both SPCs of a drug pair, 241 (61.3%) were present when the drug entered the market and 152 (30.7%) appeared in the postmarketing phase. The mention of ADRs in the SPCs of both same-class drugs in the postmarketing phase was associated with type A ADRs, marketing in the same regulator country, a longer time interval between entry into the market by the two drugs, and an earlier date of ADR. Although there appears to be some degree of safety learning from same-class drugs, there is still room for improvement, possibly by increasing proactive risk management.

Moderate correlation between quality of life and disease activity in adult patients with atopic dermatitis.

BACKGROUND: Studies assessing the relationship between disease activity and quality of life (QoL) in adults with atopic dermatitis (AD), before and after therapy are lacking. The relation between disease activity and QoL in AD patients was evaluated before (t = 0) and after 6 weeks (t = 6) of treatment with cyclosporin 5 mg/kg. METHODS: In 54 patients with severe AD, disease activity was assessed using objective Scoring Atopic Dermatitis index (SCORAD), Six Area Six Sign Atopic Dermatitis (SASSAD), 'rule of nines' extent score and serum levels of thymus and activation-regulated chemokine (TARC). Patients filled out the Dermatology Life Quality Index (DLQI). To study the relation between disease activity and QoL, correlations were calculated and regression analysis was performed. RESULTS: At t = 0 there was a small, non-significant correlation between the DLQI and the objective SCORAD, 'rule of nines' or serum TARC levels. At t = 6 the objective SCORAD, serum TARC and the 'rule of nines' score showed moderate and significant correlations with the DLQI (r = 0.34, P = 0.02; r = 0.31, P = 0.03; r = 0.49, P < 0.001). An individual's improvement in disease activity (objective SCORAD, SASSAD and 'rule of nines') with 10 points was associated with an improvement of 1.3, 1.5 and 1.1 points respectively in DLQI. CONCLUSIONS: Disease activity correlated better with QoL when disease activity was less severe and disease extent ('rule of nines') correlated better with QoL than disease severity. An individual's improvement of 10 points in disease activity was accompanied by only a small improvement in QoL. Other factors than disease activity may influence QoL in patients with AD.

E-health in caring for patients with atopic dermatitis: a randomized controlled cost-effectiveness study of internet-guided monitoring and online self-management training.

BACKGROUND: The Dermatology Department of the University Medical Centre Utrecht, the Netherlands, developed an e-health portal for patients with atopic dermatitis (AD), consisting of e-consultation, a patient-tailored website, monitoring and self-management training. OBJECTIVES: To determine the cost-effectiveness of individualized e-health compared with usual face-to-face care for children and adults with AD. METHODS: A randomized controlled cost-effectiveness study from a societal perspective in adults and parents of children with moderate AD. Outcomes were quality of life, severity of AD, itching and direct and indirect costs. Data were collected at baseline and at 3 and 12 months after randomization. Linear mixed models were used to analyse clinical outcomes. After multiple imputation of missing data, costs and differences in costs were calculated over a period of 1 year. RESULTS: In total, 199 patients were included. There were no significant differences in disease-specific quality of life, severity of AD and intensity of itching between both groups at the three time points. The difference in direct costs between the intervention and control groups was €24 [95% confidence interval (CI) -360 to 383], whereas this difference was -€618 (95% CI -2502 to 1143) for indirect costs. Overall, individual e-health was expected to save €594 (95% CI -2545 to 1227) per patient in the first year of treatment, mainly through a reduction in work absenteeism. Uncertainty analyses revealed that the probability of e-health reducing costs was estimated to be ≥ 73%. CONCLUSIONS: E-health during follow-up of patients with AD is, after initial diagnosis and treatment during face-to-face contact, just as effective as usual face-to-face care with regard to quality of life and severity of disease. However, when costs are considered, e-health is likely to result in substantial cost savings. Therefore, e-health is a valuable service for patients with AD.

Diagnostic value of hazelnut allergy tests including rCor a 1 spiking in double-blind challenged children.

BACKGROUND: The diagnostic value of hazelnut allergy tests in double-blind challenged children is largely unknown. The aim of this study was to analyze the performance of current diagnostic tests for hazelnut allergy in children and the effect of spiking. METHODS: Data of 151 children who underwent a double-blind placebo-controlled food challenge for hazelnut were analyzed. The positive predictive value and negative predictive value (PPV/NPV) of level of specific IgE (sIgE) for hazelnut, the influence of rCor a 1 spiking of the ImmunoCAP, and size of the skin prick test (SPT) for hazelnut were determined, also in relation to the severity of the hazelnut allergy. Reported accidental ingestion leading to an allergic reaction to hazelnut was also analyzed in relation to hazelnut allergy. RESULTS: Specific IgE ≥0.35 kU(A) /l for hazelnut was a moderate predictor for hazelnut allergy. The spiking decreased the PPV from 41% to 38% and increased the NPV from 91% to 100% for sIgE ≥0.35 kU(A) /l. The maximum reached PPV was 73% for sIgE cutoff of 26 kU(A) /l. Level of sIgE before spiking was significantly different between different grades of severity and was lost after spiking. Skin prick test was a better predictor for hazelnut allergy and severity than the level of sIgE. A history of accidental ingestion leading to an allergic reaction to hazelnut had a predictive value of 59% for hazelnut allergy. CONCLUSIONS: This study showed a good NPV of diagnostic tests for hazelnut allergy in children which further improved by rCor a 1 spiking. However, the PPVs are moderate and decreased by spiking.