HAE patient self-sampling for biomarker establishment.

BACKGROUND: Hereditary Angioedema (HAE) is a genetic disorder that leads to frequent angioedema attacks in various parts of the body. In most cases it is caused by pathogenic variants in the SERPING1 gene, coding for C1-Inhibitor (C1-INH). The pathogenic variants in the gene result in reduced C1-INH levels and/or activity, which causes aberrant bradykinin production and enhanced vascular permeability. The standard-of-care diagnostic test is performed biochemically via measuring C1-INH level and activity as well as the C4 level. This, however, does not allow for the diagnosis of HAE types with normal C1-INH. There is an urgent need to identify and characterize HAE biomarkers for facilitating diagnostics and personalizing the treatment. The Hereditary Angioedema Kininogen Assay (HAEKA) study aims to measure the dynamics of cleaved High Molecular Weight Kininogen (HKa) and other metabolite levels during the angioedema and non-angioedema state of the disease. The metabolites will be analyzed and verified by liquid chromatography ion mobility high resolution mass spectrometry (LC/IM-QToF MS) of dried blood spot (DBS) cards upon the study completion. The study design is truly innovative: 100 enrolled participants provide blood samples via DBS: (1) every 3 months within 2 years during regular study site visits and (2) by at-home self-sampling during HAE attacks via finger pricking. We are presenting a project design that permits clinical study activities during pandemic contact restrictions and opens the door for other clinical studies during COVID-19. RESULTS: As of October 2020, there are 41 patients from 5 sites in Germany enrolled. 90 blood samples were collected during the regular visits, and 19 of the participants also performed self-sampling during the HAE attacks from which a total of 286 attack blood samples were collected. Participating patients rate the study procedures as easy to implement in their daily lives. The concept of home self-sampling is effective, reproducible, and convenient especially in times of contact restrictions due to the COVID-19 pandemic. CONCLUSIONS: It is the hope that the HAEKA study will complete in 2023, reveal biomarker(s) for monitoring HAE disease activity, and may help to avoid HAE attacks via applying medication prior to the symptom onset.

The Rostock International Parkinson's Disease (ROPAD) Study: Protocol and Initial Findings.

BACKGROUND: Genetic stratification of Parkinson's disease (PD) patients facilitates gene-tailored research studies and clinical trials. The objective of this study was to describe the design of and the initial data from the Rostock International Parkinson's Disease (ROPAD) study, an epidemiological observational study aiming to genetically characterize ~10,000 participants. METHODS: Recruitment criteria included (1) clinical diagnosis of PD, (2) relative of participant with a reportable LRRK2 variant, or (3) North African Berber or Ashkenazi Jew. DNA analysis involved up to 3 successive steps: (1) variant (LRRK2) and gene (GBA) screening, (2) panel sequencing of 68 PD-linked genes, and (3) genome sequencing. RESULTS: Initial data based on the first 1360 participants indicated that the ROPAD enrollment strategy revealed a genetic diagnostic yield of ~14% among a PD cohort from tertiary referral centers. CONCLUSIONS: The ROPAD screening protocol is feasible for high-throughput genetic characterization of PD participants and subsequent prioritization for gene-focused research efforts and clinical trials. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

[Series of risk of bias assessment (5): Risk Of Bias In Non-randomized Studies-of Interventions (ROBINS-I)].

This paper summaries the Risk Of Bias In Non-randomized Studies-of Interventions (ROBINS-I), a tool for evaluating risk of bias about Non-randomized Studies-of Interventions (NRSI), and introduces the application of ROBINS-I in a published NRSI. According to the characteristics of NRSI, evaluation field and signaling question were designed in ROBINS-I to provide essential information about risk of bias for NRSI included in systematic reviews. ROBINS-I is the tool in assessment of risk of bias in observational studies and quasi-randomised studies. Although the tool has been used in practice to some extent, but it still needs further improvement. Attention should be paid to its update and progress.

Series of risk of bias assessment (5): Risk Of Bias In Non-randomized Studies-of Interventions (ROBINS-I) / 中华流行病学杂志

This paper summaries the Risk Of Bias In Non-randomized Studies-of Interventions (ROBINS-I),a tool for evaluating risk of bias about Non-randomized Studies-of Interventions (NRSI),and introduces the application of ROBINS-I in a published NRSI.According to the characteristics of NRSI,evaluation field and signaling question were designed in ROBINS-I to provide essential information about risk of bias for NRSI included in systematic reviews.ROBINS-I is the tool in assessment of risk of bias in observational studies and quasi-randomised studies.Although the tool hasbeen used in practice to some extent,but it still needs further improvement.Attention should be paid to its update and progress.

Series of risk of bias assessment (5): Risk Of Bias In Non-randomized Studies-of Interventions (ROBINS-I) / 中华流行病学杂志

This paper summaries the Risk Of Bias In Non-randomized Studies-of Interventions (ROBINS-I),a tool for evaluating risk of bias about Non-randomized Studies-of Interventions (NRSI),and introduces the application of ROBINS-I in a published NRSI.According to the characteristics of NRSI,evaluation field and signaling question were designed in ROBINS-I to provide essential information about risk of bias for NRSI included in systematic reviews.ROBINS-I is the tool in assessment of risk of bias in observational studies and quasi-randomised studies.Although the tool hasbeen used in practice to some extent,but it still needs further improvement.Attention should be paid to its update and progress.