Major Allergen Content in Allergen Immunotherapy Products: The Limited Value of Numbers

The prevalence of allergic disorders has increased drastically over the last 50 years to the extent that they can be considered epidemic. At present, allergen-specific immunotherapy (AIT) is the only therapy that targets the underlying cause of allergic disorders, and evidence of its superiority is based on data accumulated from clinical trials and observational studies demonstrating efficacy and safety. However, several aspects remain unresolved, such as harmonization and standardization of manufacturing and quantification procedures across manufacturers, homogeneous reporting of strength, and the establishment of international reference standards for many allergens. This article discusses issues related to the measurement of major allergen content in AIT extracts, raising the question of whether comparison of products from different manufacturers is an appropriate basis for selecting a specific AIT product. Allergen standardization in immunotherapy products is critical for ensuring quality and, thereby, safety and efficacy. However, lack of harmonization in manufacturing processes, allergen quantification (methodologies and references), national regulatory differences, clinical practice, and labeling shows that the comparison of AIT products based solely on major allergen amounts is not rational and, in fact, impossible. Moreover, when rating the information given for a specific product, it is necessary to take into account further inherent characteristics of products and their application in clinical practice, such as the state of extract modification, addition of adjuvant or adjuvant system, route of administration (sublingual/ subcutaneous), and cumulative dose as per posology (including the volume per administration). Finally, only convincing clinical data can serve as the basis for product-specific evaluation and cross-product comparability of individual products

Formal support for informal caregivers to older persons with dementia through the course of the disease: an exploratory, cross-sectional study

Background: In European countries, knowledge about availability and utilization of support for informal caregivers caring for older persons (>= 65 years) with dementia (PwD) is lacking. To be able to evaluate and develop the dementia support system for informal caregivers to PwD, a survey of European support systems and professionals involved is needed. The aim of this study was to explore support for informal caregivers to PwD in European countries. We investigated the availability and utilization of support in each of the participating countries, and the professional care providers involved, through the dementia disease. Methods: A mapping system was used in 2010-2011 to gather information about estimations of availability, utilization, and professional providers of support to informal caregivers caring for PwD. Data collected was representing each country as a whole. Results: There was high availability of counselling, caregiver support, and education from the diagnosis to the intermediate stage, with a decrease in the late to end of life stage. Utilization was low, although there was a small increase in the intermediate stage. Day care and respite care were highly available in the diagnosis to the intermediate stage, with a decrease in the late to end of life stage, but both types of care were utilized by few or no caregivers through any of the disease stages. Professionals specialized in dementia (Bachelor to Master's degree) provided counselling and education, whereas caregiver support for informal caregivers and day care, respite care, and respite care at home were provided by professionals with education ranging from upper secondary schooling to a Master's degree. Conclusions: Counselling, caregiver support, and education were highly available in European countries from diagnosis to the intermediate stage of the dementia disease, decreasing in the late/end of life stages but were rarely utilized. Countries with care systems based on national guidelines for dementia care seem to be more aware of the importance of professionals specialized in dementia care when providing support to informal caregivers. Mapping the systems of support for informal caregivers of PwD is a valuable tool for evaluating existing systems, internationally, nationally and locally for policy making

A Randomised controlled trial of Energetic Activity for Depression in Young people (READY): A multi-site feasibility trial protocol

Background: Prevalence of depression is increasing in young people, and there is a need to develop and evaluate behavioural interventions which may provide benefits equal to or greater than talking therapies or pharmacological alternatives. Exercise could be beneficial for young people living with depression, but robust, large-scale trials of effectiveness and the impact of exercise intensity are lacking. This study aims to test whether a randomised controlled trial (RCT) of an intervention targeting young people living with depression is feasible by determining whether it is possible to recruit and retain young people, develop and deliver the intervention as planned, and evaluate training and delivery. Methods: The design is a three-arm cluster randomised controlled feasibility trial with embedded process evaluation. Participants will be help-seeking young people, aged 13–17 years experiencing mild to moderate low mood or depression, referred from three counties in England. The intervention will be delivered by registered exercise professionals, supported by mental health support workers, twice a week for 12 weeks. The three arms will be high-intensity exercise, low-intensity exercise, and a social activity control. All arms will receive a ‘healthy living’ behaviour change session prior to each exercise session and the two exercise groups are energy matched. The outcomes are referral, recruitment, and retention rates; attendance at exercise sessions; adherence to and ability to reach intensity during exercise sessions; proportions of missing data; adverse events, all measured at baseline, 3, and 6 months; resource use; and reach and representativeness. Discussion: UK National Health Service (NHS) policy is to provide young people with advice about using exercise to help depression but there is no evidence-based exercise intervention to either complement or as an alternative to medication or talking therapies. UK National Institute for Health and Care Excellence (NICE) guidelines suggest that exercise can be an effective treatment, but the evidence base is relatively weak. This feasibility trial will provide evidence about whether it is feasible to recruit and retain young people to a full RCT to assess the effectiveness and cost-effectiveness of an exercise intervention for depression. Trial registration: ISRCTN, ISRCTN66452702. Registered 9 April 2020

A claims data-based comparison of comorbidity in individuals with and without dementia.

BACKGROUND: Multimorbidity is common in advanced age, and is usually associated with negative - yet to some extent preventable - health outcomes. Detecting comorbid conditions is especially difficult in individuals with dementia, as they might not always be able to sufficiently express discomfort. This study compares relevant comorbidity complexes in elderly people with and without dementia, with a particular look at gender- and living environment-specific differences. Moreover, associations between selected comorbid conditions and dementia are reviewed more closely. METHODS: Using 2006 claims data from a large German Statutory Health Insurance fund, 9,139 individuals with dementia and 28,614 age- and gender-matched control subjects aged 65 years and older were identified. A total of 30 comorbidity complexes were defined based on ICD-10 codes. Corresponding prevalence rates were calculated, and the association between a distinct condition and dementia was evaluated via logistic regression in the overall sample as well as in analyses stratified by gender and living environment. RESULTS: Individuals with dementia were more likely to be diagnosed with 15 comorbidity complexes, including Parkinson's, stroke, diabetes, atherosclerosis (supposed dementia risk factors) or fluids and electrolyte disorders, insomnia, incontinence, pneumonia, fractures and injuries (supposed sequelae). In contrast, they were less likely to be diagnosed with 11 other conditions, which included vision and hearing problems, diseases of the musculoskeletal system, lipoprotein disorders and hypertension. In a gender-stratified analysis, the patterns remained largely the same, but a bigger comorbidity gap between cases and control subjects emerged in the male population. Restricting the analysis to community-living individuals did not lead to any substantial changes. CONCLUSION: Besides strengthening the evidence on accepted dementia risk factors and sequelae, the analyses point to particular conditions that are likely to remain untreated or even undiagnosed. This issue seems to affect male and female individuals with dementia to varying degrees. Raising awareness of these conditions is important to possibly preventing comorbidity-associated complications and disease progression in dementia patients. To more comprehensively understand the mutual interactions between dementia and comorbidity, further research on diagnostic and treatment attitudes regarding comorbidity in dementia patients and on their gender-specific health-seeking behaviour seems to be required. &nbsp

Cost-effectiveness of a non-pharmacological treatment vs. “care as usual” in day care centers for community-dwelling older people with cognitive impairment: Results from the German randomized controlled DeTaMAKS-trial.

Background: Cognitive impairment in older adults causes a high economic and societal burden. This study assesses the cost-effectiveness of the multicomponent, non-pharmacological MAKS treatment vs. “care as usual” in German day care centers (DCCs) for community-dwelling people with mild cognitive impairment (MCI) or mild to moderate dementia over 6 months. Methods: The analysis was conducted from the societal perspective alongside the cluster-randomized controlled, multicenter, prospective DeTaMAKS-trial with waitlist group design. Outcomes were Mini-Mental Status Examination (MMSE) and Erlangen Test of Activities of Daily Living in Persons with Mild Dementia or Mild Cognitive Impairment (ETAM) of 433 individuals in 32 DCCs. Incremental differences in MMSE and ETAM were calculated via a Gaussian-distributed and incremental cost difference via a Gamma-distributed Generalized Linear Model. Cost-effectiveness was assessed via cost-effectiveness planes and cost-effectiveness acceptability curves (CEAC). Results: At 6 months, MMSE (adjusted mean difference = 0.92; 95% confidence interval (CI): 0.17 to 1.67; p = 0.02) and ETAM (adjusted mean difference = 1.00; CI: 0.14 to 1.85; p = 0.02) were significantly better in the intervention group. The adjusted cost difference was − €938.50 (CI: − 2733.65 to 763.13; p = 0.31). Given the CEAC, MAKS was cost-effective for 78.0% of MMSE and 77.4% for ETAM without a need for additional costs to payers. Conclusions: MAKS is a cost-effective treatment to stabilize the ability to perform activities of daily living and cognitive abilities of people with MCI or mild to moderate dementia in German DCCs. Thus, MAKS should be implemented in DCCs