Project DECIDE, part 1: increasing the amount of valid advance directives in people with Alzheimer’s disease by offering advance care planning - a prospective double-arm intervention study

Finanziert im Rahmen der DEAL-Verträge durch die Universitätsbibliothek SiegenBackground Everybody has the right to decide whether to receive specific medical treatment or not and to provide their free, prior and informed consent to do so. As dementia progresses, people with Alzheimer’s dementia (PwAD) can lose their capacity to provide informed consent to complex medical treatment. When the capacity to consent is lost, the autonomy of the affected person can only be guaranteed when an interpretable and valid advance directive exists. Advance directives are not yet common in Germany, and their validity is often questionable. Once the dementia diagnosis has been made, it is assumed to be too late to write an advance directive. One approach used to support the completion of advance directives is ‘Respecting Choices’®—an internationally recognised, evidence-based model of Advance Care Planning (ACP), which, until now, has not been evaluated for the target group of PwAD. This study’s aims include (a) to investigate the proportion of valid advance directives in a memory clinic population of persons with suspected AD, (b) to determine the predictors of valid advance directives, and (c) to examine whether the offer of ACP can increase the proportion of valid advance directives in PwAD. Method We intend to recruit at least N = 250 participants from two memory clinics in 50 consecutive weeks. Of these, the first 25 weeks constitute the baseline phase (no offer of ACP), the following 25 weeks constitute the intervention phase (offer of ACP). The existence and validity of an advance directive will be assessed twice (before and after the memory clinic appointment). Moreover, potential predictors of valid advance directives are assessed. Discussion The results of this study will enhance the development of consent procedures for advance directives of PwAD based on the ACP/Respecting Choices (R) approach. Therefore, this project contributes towards increasing the autonomy and inclusion of PwAD and the widespread acceptance of valid advance directives in PwAD

Regional opening strategies with commuter testing and containment of new SARS-CoV-2 variants

Background Despite the accelerating vaccination process, a large majority of the population is still susceptible to SARS-CoV-2. In addition, we face the spread of novel variants. Until we overcome the pandemic, reasonable mitigation and opening strategies are crucial to balance public health and economic interests. Methods We model the spread of SARS-CoV-2 over the German counties by a graph-SIR-type model with particular focus on commuter testing. We account for political interventions by varying contact reduction values in private and public locations such as homes, schools, workplaces, and other. We consider different levels of lockdown strictness, commuter testing strategies, or the delay of intervention implementation. We conduct numerical simulations to assess the effectiveness of the different intervention strategies after one month. The virus dynamics in the counties are initialized randomly with incidences between 75-150 weekly new cases per 100,000 inhabitants (red zones) or below 10 (green zones) and consider 25 different initial scenarios of randomly distributed red zones (between 2 and 20 % of all counties). To account for uncertainty, we consider an ensemble set of 500 Monte Carlo runs for each scenario. Results We find that the strength of the lockdown in regions with out of control virus dynamics is most important to avoid the spread into neighboring regions. With very strict lockdowns in red zones, commuter testing rates of twice a week can substantially contribute to the safety of adjacent regions. In contrast, less strict lockdowns with the same commuter testing rate quickly and substantially lead to overall higher infection dynamics. A further key contributor is the potential delay of the intervention implementation. In order to keep the spread of the virus under control, strict regional lockdowns with minimum delay and commuter testing of at least twice a week are advisable

Regional opening strategies with commuter testing and containment of new SARS-CoV-2 variants in Germany

Background Despite the vaccination process in Germany, a large share of the population is still susceptible to SARS-CoV-2. In addition, we face the spread of novel variants. Until we overcome the pandemic, reasonable mitigation and opening strategies are crucial to balance public health and economic interests. Methods We model the spread of SARS-CoV-2 over the German counties by a graph-SIR-type, metapopulation model with particular focus on commuter testing. We account for political interventions by varying contact reduction values in private and public locations such as homes, schools, workplaces, and other. We consider different levels of lockdown strictness, commuter testing strategies, or the delay of intervention implementation. We conduct numerical simulations to assess the effectiveness of the different intervention strategies after one month. The virus dynamics in the regions (German counties) are initialized randomly with incidences between 75 and 150 weekly new cases per 100,000 inhabitants (red zones) or below (green zones) and consider 25 different initial scenarios of randomly distributed red zones (between 2 and 20% of all counties). To account for uncertainty, we consider an ensemble set of 500 Monte Carlo runs for each scenario. Results We find that the strength of the lockdown in regions with out of control virus dynamics is most important to avoid the spread into neighboring regions. With very strict lockdowns in red zones, commuter testing rates of twice a week can substantially contribute to the safety of adjacent regions. In contrast, the negative effect of less strict interventions can be overcome by high commuter testing rates. A further key contributor is the potential delay of the intervention implementation. In order to keep the spread of the virus under control, strict regional lockdowns with minimum delay and commuter testing of at least twice a week are advisable. If less strict interventions are in favor, substantially increased testing rates are needed to avoid overall higher infection dynamics. Conclusions Our results indicate that local containment of outbreaks and maintenance of low overall incidence is possible even in densely populated and highly connected regions such as Germany or Western Europe. While we demonstrate this on data from Germany, similar patterns of mobility likely exist in many countries and our results are, hence, generalizable to a certain extent

Genetic landscape of congenital insensitivity to pain and hereditary sensory and autonomic neuropathies

Congenital insensitivity to pain (CIP) and hereditary sensory and autonomic neuropathies (HSAN) are clinically and genetically heterogeneous disorders exclusively or predominantly affecting the sensory and autonomic neurons. Due to the rarity of the diseases and findings based mainly on single case reports or small case series, knowledge about these disorders is limited. Here, we describe the molecular workup of a large international cohort of CIP/HSAN patients including patients from normally under-represented countries. We identify 80 previously unreported pathogenic or likely pathogenic variants in a total of 73 families in the >20 known CIP/HSAN-associated genes. The data expand the spectrum of disease-relevant alterations in CIP/HSAN, including novel variants in previously rarely recognized entities such as ATL3-, FLVCR1- and NGF-associated neuropathies and previously under-recognized mutation types such as larger deletions. In silico predictions, heterologous expression studies, segregation analyses and metabolic tests helped to overcome limitations of current variant classification schemes that often fail to categorize a variant as disease-related or benign. The study sheds light on the genetic causes and disease-relevant changes within individual genes in CIP/HSAN. This is becoming increasingly important with emerging clinical trials investigating subtype or gene-specific treatment strategies