The qualification of an enrichment biomarker for clinical trials targeting early stages of Parkinson’s disease

As therapeutic trials target early stages of Parkinson’s disease (PD), appropriate patient selection based purely on clinical criteria poses significant challenges. Members of the Critical Path for Parkinson’s Consortium formally submitted documentation to the European Medicines Agency (EMA) supporting the use of Dopamine Transporter (DAT) neuroimaging in early PD. Regulatory documents included a comprehensive literature review, a proposed analysis plan of both observational and clinical trial data, and an assessment of biomarker reproducibility and reliability. The research plan included longitudinal analysis of the Parkinson Research Examination of CEP-1347 Trial (PRECEPT) and the Parkinson’s Progression Markers Initiative (PPMI) study to estimate the degree of enrichment achieved and impact on future trials in subjects with early motor PD. The presence of reduced striatal DAT binding based on visual reads of single photon emission tomography (SPECT) scans in early motor PD subjects was an independent predictor of faster decline in UPDRS Parts II and III as compared to subjects with scans without evidence of dopaminergic deficit (SWEDD) over 24 months. The EMA issued in 2018 a full Qualification Opinion for the use of DAT as an enrichment biomarker in PD trials targeting subjects with early motor symptoms. Exclusion of SWEDD subjects in future clinical trials targeting early motor PD subjects aims to enrich clinical trial populations with idiopathic PD patients, improve statistical power, and exclude subjects who are unlikely to progress clinically from being exposed to novel test therapeutics

International Consensus Statement on Rhinology and Allergy: Rhinosinusitis

Background: The 5 years since the publication of the first International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR‐RS) has witnessed foundational progress in our understanding and treatment of rhinologic disease. These advances are reflected within the more than 40 new topics covered within the ICAR‐RS‐2021 as well as updates to the original 140 topics. This executive summary consolidates the evidence‐based findings of the document. Methods: ICAR‐RS presents over 180 topics in the forms of evidence‐based reviews with recommendations (EBRRs), evidence‐based reviews, and literature reviews. The highest grade structured recommendations of the EBRR sections are summarized in this executive summary. Results: ICAR‐RS‐2021 covers 22 topics regarding the medical management of RS, which are grade A/B and are presented in the executive summary. Additionally, 4 topics regarding the surgical management of RS are grade A/B and are presented in the executive summary. Finally, a comprehensive evidence‐based management algorithm is provided. Conclusion: This ICAR‐RS‐2021 executive summary provides a compilation of the evidence‐based recommendations for medical and surgical treatment of the most common forms of RS

Voyage en Egypte des années 1589,1590 1591......Le Hollandais jan Sommer

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Molecular Neuroimaging of the Dopamine Transporter as a Patient Enrichment Biomarker for Clinical Trials for Early Parkinson's Disease

The Critical Path for Parkinson's (CPP) Imaging Biomarker and Modeling and Simulation working groups aimed to achieve qualification opinion by the European Medicines Agency (EMA) Committee for Medical Products for Human Use (CHMP) for the use of baseline dopamine transporter neuroimaging for patient selection in early Parkinson's disease clinical trials. This paper describes the regulatory science strategy to achieve this goal. CPP is an international consortium of three Parkinson's charities and nine pharmaceutical partners, coordinated by the Critical Path Institute

Risk and resilience: The moderating role of social coping for maternal mental health in a setting of political conflict:The moderating role of social coping for maternal mental health in a setting of political conflict

Violence can threaten individual well-being and tear at the social fabric of communities. At the same time, suffering can mobilize social coping and mutual support. Thus, the backdrop of political violence increases risk factors and stimulates resilience. The current study examined the moderating role of social coping as reflective of risk and resiliency in Northern Ireland, a setting of protracted conflict. Specifically, structural equation modeling was used to investigate whether social coping protects from or exacerbates the negative impact of sectarian crime and nonsectarian crime on maternal mental health (N=631). Nonsectarian crime predicted greater psychological distress for mothers in Belfast. Mixed support was found for the buffering and depletion moderation hypotheses; social coping functioned differently for nonsectarian crime and sectarian crime. Greater social coping buffered mothers’ psychological distress from the negative effects of nonsectarian crime, but exacerbated maternal mental health problems when facing sectarian crime. Results suggest that social coping is a complex phenomenon, particularly in settings of protracted political violence. Implications for interventions aimed at alleviating psychological distress by enhancing mothers’ social coping in contexts of intergroup conflict are discussed