Adolescent and parental decision-making for the MenACWY vaccination: influential predictors and parental-adolescent differences among households in the Netherlands.

BACKGROUND: Between 2015 and 2018 The Netherlands experienced increases of invasive meningococcal disease (IMD) serogroup W (MenW). Therefore in 2018 the MenACWY vaccination was introduced in the National Immunisation Programme (NIP) and a catch-up campaign was initiated targeting adolescents. This study aimed to gain insight into what factors played a role in the decision-making process regarding the MenACWY vaccination. The focus was on the differences in the decision-making of parents and adolescents in order to assess what factors influence the decisions made. METHODS: An online questionnaire was offered to adolescents and one of their parents. We used random forest analyses to determine which factors best predict the outcome of the MenACWY vaccination decision. We carried out ROC (receiver-operator characteristics) analyses to confirm the predictive value of the variables. RESULTS: Among parents several factors stand out, centring on the process of the decision, their attitude about the MenACWY vaccination, trust in the vaccination, and ideas of important people around them. Among adolescents the three stand-out predictors are the ideas of important people around them, the process of the decision and trust in the vaccination. Parents have prominent influence in the decision-making, while the adolescent's influence in the household decision-making is more limited. Adolescents tend to be less engaged and spend less time thinking about the decision compared to parents. Opinions of parents and adolescents from the same households concerning the factors that are influential do not differ a lot in the final decision-making. CONCLUSIONS: Information about MenACWY vaccination might be mainly addressed to the parents of the adolescents and whereby the dialogue about MenACWY vaccination between parents and adolescents will be stimulated. With regard to the predictor trust in vaccination, raising the frequency of use of certain sources, especially those deemed very reliable among households such as conversations with a GP or the provider of the vaccination (GGD/JGZ), might prove a useful strategy to solidify vaccination uptake numbers.

A single dose of doxycycline after an ixodes ricinus tick bite to prevent Lyme borreliosis: An open-label randomized controlled trial.

OBJECTIVES: A single dose of doxycycline after a tick bite can prevent the development of Lyme borreliosis in North America, but extrapolation to Europe is hampered by differences in Borrelia burgdorferi sensu lato genospecies and tick species. We assessed the efficacy of prophylaxis after a tick bite in Europe. METHODS: We conducted an open-label randomized controlled trial, administering a single dose of 200 mg doxycycline within 72 h after removing an attached tick from the skin, compared to no treatment. Potential participants ≥ 8 years of age who reported a recent tick bite online were invited for the study. After informed consent, they were randomly assigned to either the prophylaxis or the no-treatment group. Participants in the prophylaxis group were asked to visit their general practitioner to administer the antibiotics. All participants were followed up by online questionnaires. Our primary outcome was the development of physician-confirmed Lyme borreliosis in a modified-intention-to-treat analysis. This study is registered in the Netherlands Trial Register (NTR3953) and is closed. RESULTS: Between April 11, 2013, and June 10, 2015, 3538 potential participants were randomized, of whom 1689 were included in the modified-intention-to-treat analysis. 10 cases of Lyme borreliosis were reported out of 1041 participants (0.96%) in the prophylaxis group, and 19 cases out of 648 no-treatment participants (2.9%), resulting in a relative risk reduction of 67% (95% CI 31 - 84%), and a number-needed-to-treat of 51 (95% CI 29 - 180). No serious adverse events were reported. CONCLUSIONS: This primary care-based trial provides evidence that a single dose of doxycycline can prevent the development of Lyme borreliosis after an Ixodes ricinus tick bite.

Prevalence and incidence of surgical site infections in the European Union/European Economic Area: how do these measures relate?

BACKGROUND: In 2011-2012, the European Centre for Disease Prevention and Control (ECDC) initiated the first European point prevalence survey (PPS) of healthcare-associated infections (HCAIs) in addition to targeted surveillance of the incidence of specific types of HCAI such as surgical site infections (SSIs). AIM: To investigate whether national and multi-country SSI incidence can be estimated from ECDC PPS data. METHODS: In all, 159 hospitals were included from 15 countries that participated in both ECDC surveillance modules, aligning surgical procedures in the incidence surveillance to corresponding specialties from the PPS. National daily prevalence of SSIs was simulated from the incidence surveillance data, the Rhame and Sudderth (R&S) formula was used to estimate national and multi-country SSI incidence from the PPS data, and national incidence per specialty was predicted using a linear model including data from the PPS. FINDINGS: The simulation of daily SSI prevalence from incidence surveillance of SSIs showed that prevalence fluctuated randomly depending on the day of measurement. The correlation between the national aggregated incidence estimated with R&S formula and observed SSI incidence was low (correlation coefficient = 0.24), but specialty-specific incidence results were more reliable, especially when the number of included patients was large (correlation coefficients ranging from 0.40 to 1.00). The linear prediction model including PPS data had low proportion of explained variance (0.40). CONCLUSION: Due to a lack of accuracy, use of PPS data to estimate SSI incidence is recommended only in situations where incidence surveillance of SSIs is not performed, and where sufficiently large samples of PPS data are available.

Omalizumab for Severe Asthma: Beyond Allergic Asthma.

Different subsets of asthma patients may be recognized according to the exposure trigger and the frequency and severity of clinical signs and symptoms. Regarding the exposure trigger, generally asthma can be classified as allergic (or atopic) and nonallergic (or nonatopic). Allergic and nonallergic asthma are distinguished by the presence or absence of clinical allergic reaction and in vitro IgE response to specific aeroallergens. The mechanisms of allergic asthma have been extensively studied with major advances in the last two decades. Nonallergic asthma is characterized by its apparent independence from allergen exposure and sensitization and a higher degree of severity, but little is known regarding the underlying mechanisms. Clinically, allergic and nonallergic asthma are virtually indistinguishable in exacerbations, although exacerbation following allergen exposure is typical of allergic asthma. Although they both show several distinct clinical phenotypes and different biomarkers, there are no ideal biomarkers to stratify asthma phenotypes and guide therapy in clinical practice. Nevertheless, some biomarkers may be helpful to select subsets of atopic patients which might benefit from biologic agents, such as omalizumab. Patients with severe asthma, uncontrolled besides optimal treatment, notwithstanding nonatopic, may also benefit from omalizumab therapy, although currently there are no randomized double-blind placebo controlled clinical trials to support this suggestion. However, omalizumab discontinuation according to each patient's response to therapy and pharmacoeconomical analysis are questions that remain to be answered.

A functional glycoproteomics approach identifies CD13 as a novel E-selectin ligand in breast cancer.

BACKGROUND: The glycan moieties sialyl-Lewis-X and/or -A (sLeX/A) are the primary ligands for E-selectin, regulating subsequent tumor cell extravasation into distant organs. However, the nature of the glycoprotein scaffolds displaying these glycans in breast cancer remains unclear and constitutes the focus of the present investigation. METHODS: We isolated glycoproteins that bind E-selectin from the CF1_T breast cancer cell line, derived from a patient with ductal carcinoma. Proteins were identified using bottom-up proteomics approach by nanoLC-orbitrap LTQ-MS/MS. Data were curated using bioinformatics tools to highlight clinically relevant glycoproteins, which were validated by flow cytometry, Western blot, immunohistochemistry and in-situ proximity ligation assays in clinical samples. RESULTS: We observed that the CF1_T cell line expressed sLeX, but not sLeA and the E-selectin reactivity was mainly on N-glycans. MS and bioinformatics analysis of the targeted glycoproteins, when narrowed down to the most clinically relevant species in breast cancer, identified CD44 glycoprotein (HCELL) and CD13 as key E-selectin ligands. Additionally, the co-expression of sLeX-CD44 and sLeX-CD13 was confirmed in clinical breast cancer tissue samples. CONCLUSIONS: Both CD44 and CD13 glycoforms display sLeX in breast cancer and bind E-selectin, suggesting a key role in metastasis development. Such observations provide a novel molecular rationale for developing targeted therapeutics. GENERAL SIGNIFICANCE: While HCELL expression in breast cancer has been previously reported, this is the first study indicating that CD13 functions as an E-selectin ligand in breast cancer. This observation supports previous associations of CD13 with metastasis and draws attention to this glycoprotein as an anti-cancer target.

Evaluation of sedation-related medication errors in patients on contact isolation in the intensive care unit.

BACKGROUND: Patients in intensive care units (ICUs) may be placed on contact isolation for meticillin-resistant Staphylococcus aureus (MRSA) colonization to prevent transmission. Prior studies suggest that isolated patients may receive substandard care compared with non-isolated patients. An optimal level of sedation is required to facilitate mechanical ventilation (MV) and to minimize adverse outcomes. AIM: To determine if patients on MV and isolated for MRSA colonization are at increased risk of oversedation compared with non-isolated patients. METHODS: Retrospective chart review of adult patients on MV who received an MRSA nasal polymerase chain reaction assay and sedation within 24 and 48 h of ICU admission, respectively. Endpoints included rate of inappropriate sedation, length of ICU stay, length of time on MV, and incidence of ventilator-associated complications. FINDINGS: In total, 226 patients were included (114 MRSA positive, 112 MRSA negative). Baseline demographics were similar between the groups, with the exception of ICU admission diagnosis. Fifty-six (55%) isolated patients experienced inappropriate sedation compared with 49 (50%) non-isolated patients (P=0.482). Isolated patients spent longer in the ICU (10.4 vs 6.8 days, P=0.0006), longer on MV (8.98 vs 4.81 days, P<0.001), and required tracheostomies more frequently [37 (32%) vs 14 (13%), P=0.0003] than non-isolated patients. CONCLUSIONS: Isolated patients were not at increased risk of oversedation compared with non-isolated patients. There was an association between the use of contact isolation for MRSA nares colonization and prolonged ICU stay and prolonged MV.

Heat stress decreases expression of the cytokines, avian ß-defensins 4 and 6 and Toll-like receptor 2 in broiler chickens infected with Salmonella Enteritidis.

A high ambient temperature is a highly relevant stressor in poultry production. Heat stress (HS) has been reported to reduce animal welfare, performance indices and increase Salmonella susceptibility. Salmonella spp. are major zoonotic pathogen that cause over 1 billion of human infections worldwide annually. Therefore, the current study was designed to analyze the effect of heat stress on Salmonella infection in chickens through modulation of the immune responses. Salmonella Enteritidis was inoculated via gavage at one day of age (106cfu/mL). Heat stress 31±1°C was applied from 35 to 41 days of age. Broiler chickens were divided into the following groups of 12 chickens: control (C); heat stress (HS31°C); S. Enteritidis positive control (PC); and S. Enteritidis+heat stress (PHS31°C). We observed that heat stress increased corticosterone serum levels. Concomitantly heat stress decreased (1) the IgA and IFN-γ plasmatic levels; (2) the mRNA expression of IL-6, IL-12 in spleen and IL-1ß, IL-10, TGF-ß in cecal tonsils; (3) the mRNA expression of AvBD4 and AvBD6 in cecal tonsils; and (4) the mRNA expression of TLR2 in spleen and cecal tonsils of chickens infected with S. Enteritidis (PHS31°C group). Heat stress also increased Salmonella colonization in the crop and caecum as well as Salmonella invasion to the spleen, liver and bone marrow, showing a deficiency in the control of S. Enteritidis induced infection. Together, the present data suggested that heat stress activated hypothalamus-pituitary-adrenal (HPA) axis, as observed by the increase in the corticosterone levels, which in turn presumably decreases the immune system activity, leading to an impairment of the intestinal mucosal barrier and increasing chicken susceptibility to the invasion of different organs by S. Enteritidis .

Incidence of surgical site infections cannot be derived reliably from point prevalence survey data in Dutch hospitals.

Thorough studies on whether point prevalence surveys of healthcare-associated infections (HAIs) can be used to reliably estimate incidence of surgical site infections (SSIs) are scarce. We examined this topic using surveillance data of 58 hospitals that participated in two Dutch national surveillances; HAI prevalence and SSI incidence surveillance, respectively. First, we simulated daily prevalences of SSIs from incidence data. Subsequently, Rhame & Sudderth's formula was used to estimate SSI incidence from prevalence. Finally, we developed random-effects models to predict SSI incidence from prevalence and other relevant variables. The prevalences simulated from incidence data indicated that daily prevalence varied greatly. Incidences calculated with Rhame & Sudderth's formula often had values below zero, due to the large number of SSIs occurring post-discharge. Excluding these SSIs, still resulted in poor correlation between calculated and observed incidence. The two models best predicting total incidence and incidence during initial hospital stay both performed poorly (proportion of explained variance of 0·25 and 0·10, respectively). In conclusion, incidence of SSIs cannot be reliably estimated from point prevalence data in Dutch hospitals by any of the applied methods. We therefore conclude that prevalence surveys are not a useful measure to give reliable insight into incidence of SSIs.

Use of omalizumab in the treatment of chronic urticaria.

BACKGROUND: Omalizumab is indicated to treat chronic spontaneous urticaria (CSU) refractory to antihistamines. We aim to describe the experience of our department in the treatment of CSU with omalizumab. MATERIALS AND METHODS: Retrospective review of the clinical records of patients. RESULTS: Six patients (5 females, median age 33 years) treated with omalizumab for a median of 17.5 months were evaluated. All patients had improvement of symptoms after the first dose. In one case, the treatment was suspended after 7 months, but in 9 weeks there was recurrence of symptoms. The main side effect was headache in the drug administration's day. Currently, all patients maintain therapy with omalizumab and are clinically stable. CONCLUSION: Omalizumab proved to be an effective and safe drug for the treatment of patients with refractory CSU.

A coupled non-Fickian model of a cardiovascular drug delivery system.

A coupled non-Fickian model of a cardiovascular drug delivery system using a biodegradable drug-eluting stent is proposed. The numerical results are obtained using an implicit-explicit finite-element method. The influence of vessel stiffness on the transport of drug eluted from the stent is analysed. The results presented in this paper suggest new perspectives to adapt the drug delivery profile to the needs of the patient.

Mathematical modeling of efficient protocols to control glioma growth.

In this paper we propose a mathematical model to describe the evolution of glioma cells taking into account the viscoelastic properties of brain tissue. The mathematical model is established considering that the glioma cells are of two phenotypes: migratory and proliferative. The evolution of the migratory cells is described by a diffusion-reaction equation of non Fickian type deduced considering a mass conservation law with a non Fickian migratory mass flux. The evolution of the proliferative cells is described by a reaction equation. A stability analysis that leads to the design of efficient protocols is presented. Numerical simulations that illustrate the behavior of the mathematical model are included.

Recombinant biglycan promotes bone morphogenetic protein-induced osteogenesis.

The aim of this study was to determine the effects of glutathione-S-transferase-fused recombinant biglycan (GST-BGN) on craniofacial bone regeneration. We recently demonstrated a positive effect of tissue-derived BGN on bone morphogenetic protein 2 (BMP-2) function, which is exerted likely via the BGN core protein. Here, we investigated the effects of GST-BGN lacking any posttranslational modifications on BMP-2 function in vitro and in vivo. In the C2C12 cell culture system, BMP-2-induced Smad 1/5/8 phosphorylation and alkaline phosphatase activity were both enhanced by the addition of GST-BGN. For the in vivo effect, we employed a Sprague-Dawley rat mandible defect model utilizing 1 µg (optimal) or 0.1 µg (suboptimal) of BMP-2 combined with 0, 2, 4, or 8 µg of GST-BGN. At 2 weeks post-surgery, newly formed bone was evaluated by microcomputed tomography and histologic analyses. The results revealed that the greatest amounts of bone within the defect were formed in the groups of suboptimal BMP-2 combined with 4 or 8 µg of GST-BGN. Also, bone was well organized versus that formed by the optimal dose of BMP. These results indicate that recombinant BGN is an efficient substrate to promote low-dose BMP-induced osteogenesis.

Association of breast vascular calcifications with low bone mass in postmenopausal women.

BACKGROUND: In developing countries, there is a deficiency of densitometers with which to screen the population for osteoporosis. Thus, strategies with which to select patients for a bone density test are desirable. OBJECTIVE: To determine whether breast vascular calcifications (BVCs) may be employed to identify postmenopausal women with osteoporosis/osteopenia. METHODS: This was a cross-sectional study of postmenopausal women subjected to bilateral mammography and bone densitometry (DXA) of the spine and hip. A medical interview registered possible confounding factors, such as age, length of menopause, previous use of postmenopausal hormone therapy, family history of osteoporosis, smoking, alcoholism, hypertension, diabetes, cardiovascular diseases, and medication use. RESULTS: The study included 211 postmenopausal women aged 62.1 ± 9.3 years, 38 of whom (18.0%) exhibited BVC. Osteoporosis was detected in 36 (17.1%), and a T-score < 21.0 for any site was found in 164 (77.7%). No statistically significant difference was found between the groups without BVC (n = 173) and with BVC (n = 38) for the prevalence of 'osteoporosis' or 'moderate/severe osteopenia or osteoporosis' at the spine or at any other site. There was a difference between the groups in terms of age (59.0 ± 7.8 vs. 71.9 ± 8.9 years, respectively; p < 0.001), sedentary lifestyle (57.8% vs. 84.2%, respectively; p = 0.002), smoking (27.7% vs. 7.9%, respectively; p = 0.009), and high blood pressure (65.3% vs. 92.1%, respectively; p = 0.001). Logistic regression analysis confirmed the lack of statistical significance for BVC as a predictor of an osteoporosis diagnosis. Sensitivity values of BVCs to detect osteoporosis or osteopenia ranged from 17.9% to 25.0%. CONCLUSION: BVCs have been shown to be inadequate to identify postmenopausal women with osteoporosis or osteopenia.

Novel intelligent real-time position tracking system using FPGA and fuzzy logic.

The main aim of this paper is to test if FPGAs are able to achieve better position tracking performance than software-based soft real-time platforms. For comparison purposes, the same controller design was implemented in these architectures. A Multi-state Fuzzy Logic controller (FLC) was implemented both in a Xilinx(®) Virtex-II FPGA (XC2v1000) and in a soft real-time platform NI CompactRIO(®)-9002. The same sampling time was used. The comparative tests were conducted using a servo-pneumatic actuation system. Steady-state errors lower than 4 µm were reached for an arbitrary vertical positioning of a 6.2 kg mass when the controller was embedded into the FPGA platform. Performance gains up to 16 times in the steady-state error, up to 27 times in the overshoot and up to 19.5 times in the settling time were achieved by using the FPGA-based controller over the software-based FLC controller.

Response of high-risk of recurrence/progression bladder tumours expressing sialyl-Tn and sialyl-6-T to BCG immunotherapy.

BACKGROUND: High risk of recurrence/progression bladder tumours is treated with Bacillus Calmette-Guérin (BCG) immunotherapy after complete resection of the tumour. Approximately 75% of these tumours express the uncommon carbohydrate antigen sialyl-Tn (Tn), a surrogate biomarker of tumour aggressiveness. Such changes in the glycosylation of cell-surface proteins influence tumour microenvironment and immune responses that may modulate treatment outcome and the course of disease. The aim of this work is to determine the efficiency of BCG immunotherapy against tumours expressing sTn and sTn-related antigen sialyl-6-T (s6T). METHODS: In a retrospective design, 94 tumours from patients treated with BCG were screened for sTn and s6T expression. In vitro studies were conducted to determine the interaction of BCG with high-grade bladder cancer cell line overexpressing sTn. RESULTS: From the 94 cases evaluated, 36 had recurrence after BCG treatment (38.3%). Treatment outcome was influenced by age over 65 years (HR=2.668; (1.344-5.254); P=0.005), maintenance schedule (HR=0.480; (0.246-0.936); P=0.031) and multifocality (HR=2.065; (1.033-4.126); P=0.040). sTn or s6T expression was associated with BCG response (P=0.024; P<0.0001) and with increased recurrence-free survival (P=0.001). Multivariate analyses showed that sTn and/or s6T were independent predictive markers of recurrence after BCG immunotherapy (HR=0.296; (0.148-0.594); P=0.001). In vitro studies demonstrated higher adhesion and internalisation of the bacillus to cells expressing sTn, promoting cell death. CONCLUSION: s6T is described for the first time in bladder tumours. Our data strongly suggest that BCG immunotherapy is efficient against sTn- and s6T-positive tumours. Furthermore, sTn and s6T expression are independent predictive markers of BCG treatment response and may be useful in the identification of patients who could benefit more from this immunotherapy.

Simultaneous detection of hepatitis C virus antigen and antibodies in dried blood spots.

BACKGROUND: Enzyme immunoassays (EIA) designed to detect hepatitis C virus (HCV) core antigen and anti-HCV antibodies (HCV AgAb) simultaneously can improve the early detection of HCV infection when molecular diagnostic methods are not widely available. OBJECTIVES: To evaluate the suitability of dried blood spot (DBS) samples for detecting HCV AgAb using commercial EIAs. STUDY DESIGN: Paired serum and DBS samples were assayed using two commercial EIAs for HCV AgAb (Monolisa™ HCV AgAb ULTRA and Murex HCV AgAb). Manufacturer's recommendations were followed for sera while sample volume, incubation time and cut-off (CO) determination were evaluated for the DBS samples. The values of sensitivity, specificity, inter-rater agreement, detection limit, assay precision and stability of DBS samples at different conditions (22-26°C, 2-8°C and -20°C) were determined. RESULTS: It was necessary to increase the DBS sample volume fourfold compared to the sera samples to approximate the DBS Optical Density (OD) values to the sera OD values. Using ROC curve to recalculate CO values for the DBS samples, sensitivity was 97.5% for both EIAs, while the specificity was 99.71% for Monolisa™ HCV AgAb ULTRA and 95.95% for Murex HCV AgAb. Accurate testing results were obtained with DBS samples for 60 days at all conditions evaluated; storage at -20°C resulted in low OD variation. Both EIAs demonstrated the same limit of detection among DBS samples [estimated viral load of 3.1 International Units per millilitre (IU/mL)] and low OD value variability in repetitivity and reproducibility studies. CONCLUSION: DBS samples can be used for the detection of HCV AgAb by EIA as they present comparable performance characteristics and excellent stability among various storage conditions.