Judicial Review of European Administrative Procedure

Schwarze examines the requirements set down in the case law of the Court of Justice and the Court of First Instance that serve to guarantee a fair and impartial administrative process. He also considers whether improvements should be made to the design of the administrative process and, if so, what kind

Judicial Review of European Administrative Procedure

Schwarze examines the requirements set down in the case law of the Court of Justice and the Court of First Instance that serve to guarantee a fair and impartial administrative process. He also considers whether improvements should be made to the design of the administrative process and, if so, what kind

Assessment of proximal outcomes of self-management programs : translation and psychometric evaluation of a German version of the Health Education Impact Questionnaire (heiQtm)

Purpose This paper describes the translation, cultural adaption, and psychometric evaluation of a German version of the Health Education Impact Questionnaire (heiQ&trade;), a widely used generic instrument assessing a wide range of proximal outcomes of self-management programs.Methods The translation was carried out according to international standards and included forward and backward translations. Comprehensibility and content validity were tested using cognitive interviews with 10 rehabilitation inpatients. Psychometric properties were examined in rehabilitation inpatients (n = 1,202) with a range of chronic conditions. Factorial validity was assessed using confirmatory factor analysis; concurrent validity was explored by correlations with comparator scales.Results The items of the German heiQ&trade; were well understood by rehabilitation inpatients. The structure of the eight heiQ&trade; scales was replicated after minor adjustment. heiQ&trade; scales had higher correlations with comparator scales with similar constructs, particularly mental health concepts than with physical health. Moreover, all heiQ&trade; scales differentiated between individuals across different levels of depression.Conclusion The German heiQ&trade; is comprehensible for German-speaking patients suffering from different types of chronic conditions; it assesses relevant outcomes of self-management programs in a reliable and valid manner. Further studies involving its practical application are warranted.<br /

Community-based asthma assessment in young children: Adaptations for a multicentre longitudinal study in South Asia

Background: Systematic assessment of childhood asthma is challenging in low- and middle-income country (LMIC) settings due to the lack of standardised and validated methodologies. We describe the contextual challenges and adaptation strategies in the implementation of a community-based asthma assessment in four resource-constrained settings in Bangladesh, India, and Pakistan.Method: We followed a group of children of age 6-8 years for 12 months to record their respiratory health outcomes. The study participants were enrolled at four study sites of the \u27Aetiology of Neonatal Infection in South Asia (ANISA)\u27 study. We standardised the research methods for the sites, trained field staff for uniform data collection and provided a \u27Child Card\u27 to the caregiver to record the illness history of the participants. We visited the children on three different occasions to collect data on respiratory-related illnesses. The lung function of the children was assessed in the outreach clinics using portable spirometers before and after 6-minute exercise, and capillary blood was examined under light microscopes to determine eosinophil levels.Results: We enrolled 1512 children, 95.5% (1476/1512) of them completed the follow-up, and 81.5% (1232/1512) participants attended the lung function assessment tests. Pre- and post-exercise spirometry was performed successfully in 88.6% (1091/1232) and 85.7% (1056/1232) of children who attempted these tests. Limited access to health care services, shortage of skilled human resources, and cultural diversity were the main challenges in adopting uniform procedures across all sites. Designing the study implementation plan based on the local contexts and providing extensive training of the healthcare workers helped us to overcome these challenges.Conclusion: This study can be seen as a large-scale feasibility assessment of applying spirometry and exercise challenge tests in community settings of LMICs and provides confidence to build capacity to evaluate children\u27s respiratory outcomes in future translational research studies

Viral mimic poly-(I:C) attenuates airway epithelial T cell suppressive capacity; implications for asthma

In allergen-sensitised asthmatic individuals, allergen-specific type-2 T-helper cells proliferate and secrete type-2 cytokines (e.g. interleukin (IL)-4, -5 and -13), driving the airway inflammatory response that gives rise to the clinical symptoms of asthma. Both early-life sensitisation to aeroallergens and lower respiratory viral infections are important environmental risk factors for developing asthma. Additionally, respiratory viral infections are the most common trigger for asthma exacerbations. Of interest, many asthma susceptibility genes are expressed in the airway epithelium [1], which forms the first continuous line of defence against inhaled environmental insults, including viruses and aeroallergens. Impaired immune regulation and failure to maintain tolerance to allergens is thought to contribute to allergic sensitisation. Asthma epithelium may be deficient in its innate immune defence against viral infections, resulting in increased viral replication upon rhinovirus infection compared to nonasthma-derived epithelial cultures [2]. Furthermore, there is evidence for loss of the mucosal immune barrier in asthma, with disruption of epithelial integrity [1, 3]. This may lead not only to increased permeability, but also to the release of pro-inflammatory mediators, specifically of cytokines that drive type-2 responses [3, 4]. We recently observed that the ability of allergens to disrupt epithelial barrier function is related to the development of type-2-mediated inflammation in asthma [5, 6]. Furthermore, we demonstrated that healthy murine lung epithelium is a potent inhibitor of T-cell proliferation and that this inhibition is lost upon viral infection [7]. It is unknown if this immune regulatory effect is displayed by human epithelium and is dysregulated in asthma. We hypothesise that changes in this regulatory effect translate into aberrant regulation of T-cell responses in asthma. We studied the epithelial regulation of T-cell proliferation and cytokine responses upon epithelial stimulation with a viral mimic, using co-culture of human T-cells and primary bronchial epithelial cells (PBECs) from healthy controls and asthma patients

The Chemokine MIP1α/CCL3 Determines Pathology in Primary RSV Infection by Regulating the Balance of T Cell Populations in the Murine Lung

BACKGROUND: CD8 T cells assist in the clearance of respiratory syncytial virus (RSV) infection from the lungs. However, disease after RSV infection is in part caused by excessive T cell activity, and a balance is therefore needed between beneficial and harmful cellular immune responses. The chemokine CCL3 (MIP1alpha) is produced following RSV infection and is broadly chemotactic for both T cells and natural killer (NK) cells. We therefore investigated its role in RSV disease. METHODOLOGY/PRINCIPAL FINDINGS: CCL3 was produced biphasically, in both the early (day 1) and late (day 6-7) stages of infection. CCL3 depletion did not alter the recruitment of natural killer (NK) cells to the lungs during the early stage, but depletion did affect the later adaptive phase. While fewer T cells were recruited to the lungs of either CCL3 knockout or anti-CCL3 treated RSV infected mice, more RSV-specific pro-inflammatory T cells were recruited to the lung when CCL3 responses were impaired. This increase in RSV-specific pro-inflammatory T cells was accompanied by increased weight loss and illness after RSV infection. CONCLUSIONS/SIGNIFICANCE: CCL3 regulates the balance of T cell populations in the lung and can alter the outcome of RSV infection. Understanding the role of inflammatory mediators in the recruitment of pathogenic T cells to the lungs may lead to novel methods to control RSV disease

Vaccine effectiveness of live attenuated and trivalent inactivated influenza vaccination in 2010/11 to 2015/16:the SIVE II record linkage study

Background: There is good evidence of vaccine effectiveness in healthy individuals but less robust evidence for vaccine effectiveness in the populations targeted for influenza vaccination. The live attenuated influenza vaccine (LAIV) has recently been recommended for children in the UK. The trivalent influenza vaccine (TIV) is recommended for all people aged≥65 years and for those aged<65 years who are at an increased risk of complications from influenza infection (e.g. people with asthma). Objective: To examine the vaccine effectiveness of LAIV and TIV. Design: Cohort study and test-negative designs to estimate vaccine effectiveness. A self-case series study to ascertain adverse events associated with vaccination. Setting: A national linkage of patient-level general practice (GP) data from 230 Scottish GPs to the Scottish Immunisation & Recall Service, Health Protection Scotland virology database, admissions to Scottish hospitals and the Scottish death register. Participants: A total of 1,250,000 people. Interventions: LAIV for 2- to 11-year-olds and TIV for older people (aged≥65 years) and those aged<65 years who are at risk of diseases, from 2010/11 to 2015/16. Main outcome measures: The main outcome measures include vaccine effectiveness against laboratory-confirmed influenza using real-time reverse-transcription polymerase chain reaction (RT-PCR), influenza-related morbidity and mortality, and adverse events associated with vaccination. Results: Two-fifths (40%) of preschool-aged children and three-fifths (60%) of primary school-aged children registered in study practices were vaccinated. Uptake varied among groups [e.g. most affluent vs. most deprived in 2- to 4-year-olds, odds ratio 1.76, 95% confidence interval (CI) 1.70 to 1.82]. LAIV-adjusted vaccine effectiveness among children (aged 2-11 years) for preventing RT-PCR laboratoryconfirmed influenza was 21% (95% CI -19% to 47%) in 2014/15 and 58% (95% CI 39% to 71%) in 2015/16. No significant adverse events were associated with LAIV. Among at-risk 18- to 64-year-olds, significant trivalent influenza vaccine effectiveness was found for four of the six seasons, with the highest vaccine effectiveness in 2010/11 (53%, 95% CI 21% to 72%). The seasons with non-significant vaccine effectiveness had low levels of circulating influenza virus (2011/12, 5%; 2013/14, 9%). Among those people aged≥65 years, TIV effectiveness was positive in all six seasons, but in only one of the six seasons (2013/14) was significance achieved (57%, 95% CI 20% to 76%). Conclusions: The study found that LAIV was safe and effective in decreasing RT-PCR-confirmed influenza in children. TIV was safe and significantly effective in most seasons for 18- to 64-year-olds, with positive vaccine effectiveness in most seasons for those people aged≥65 years (although this was significant in only one season). Future work: The UK Joint Committee on Vaccination and Immunisation has recommended the use of adjuvanted injectable vaccine for those people aged≥65 years from season 2018/19 onwards. A future study will be required to evaluate this vaccine. Trial registration: Current Controlled Trials ISRCTN88072400