Outcome measurement in functional neurological disorder: a systematic review and recommendations.

OBJECTIVES: We aimed to identify existing outcome measures for functional neurological disorder (FND), to inform the development of recommendations and to guide future research on FND outcomes. METHODS: A systematic review was conducted to identify existing FND-specific outcome measures and the most common measurement domains and measures in previous treatment studies. Searches of Embase, MEDLINE and PsycINFO were conducted between January 1965 and June 2019. The findings were discussed during two international meetings of the FND-Core Outcome Measures group. RESULTS: Five FND-specific measures were identified-three clinician-rated and two patient-rated-but their measurement properties have not been rigorously evaluated. No single measure was identified for use across the range of FND symptoms in adults. Across randomised controlled trials (k=40) and observational treatment studies (k=40), outcome measures most often assessed core FND symptom change. Other domains measured commonly were additional physical and psychological symptoms, life impact (ie, quality of life, disability and general functioning) and health economics/cost-utility (eg, healthcare resource use and quality-adjusted life years). CONCLUSIONS: There are few well-validated FND-specific outcome measures. Thus, at present, we recommend that existing outcome measures, known to be reliable, valid and responsive in FND or closely related populations, are used to capture key outcome domains. Increased consistency in outcome measurement will facilitate comparison of treatment effects across FND symptom types and treatment modalities. Future work needs to more rigorously validate outcome measures used in this population

Opinions and clinical practices related to diagnosing and managing functional (psychogenic) movement disorders: Changes in the last decade.

BACKGROUND: There is large variability in the diagnostic approach and clinical management in functional movement disorders (FMD). This study aimed to examine whether opinions and clinical practices related to FMD have changed over the past decade. METHODS: A survey to members of the International Parkinson and Movement Disorder Society (MDS). RESULTS: We received 864/7689 responses (denominator includes non-neurologists) from 92 countries. Respondents were more often male (55%), younger than 45 (65%), and from academic practices (85%). Although the likelihood of ordering neurological investigations prior to delivering a diagnosis of FMD was nearly as high as in 2008 (47% versus 51%), the percentage of respondents communicating the diagnosis without requesting additional tests increased (27% versus 19%; p=0.003), with most envisioning their role as providing a diagnosis and coordinating management (57% versus 40%; p<0.001). Compared to patients with other disorders, 64% of respondents were more concerned about missing a diagnosis of another neurological disorder. Avoiding iatrogenic harm (58%) and educating patients about the diagnosis (53%) were again rated as the most effective therapeutic options. Frequent treatment barriers included lack of physician knowledge and training (32%), lack of treatment guidelines (39%), limited availability of referral services (48%), and cultural beliefs about psychological illnesses (50%). The preferred term for communication favored "functional" over "psychogenic" (p<0.001). CONCLUSIONS: Attitudes and management of FMD have changed over the past decade. Important gaps remain in the education of neurologists about the inclusionary approach to FMD diagnosis, and improving access to treatment

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2–4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Desastres naturais: convivência com o risco

Estudos sobre riscos de desastres naturais têm-se aprimorado de uma abordagem fisicalista para uma perspectiva socioambiental. No entanto, planejamento e gestão ainda seguem o paradigma antropocêntrico da superioridade humana e do poder ilimitado da ciência e tecnologia. Evidencia-se uma incapacidade cognitiva, cultural e de ação por parte de especialistas, científicos e tomadores de decisão (claimmakers) para identificar e atuar sobre as causas sociais da produção de risco. Frente a uma ciência cartesiana e positivista na resolução de problemas, baseada na segurança e controle sobre o mundo natural, propõe-se uma ciência pós-normal que considera os riscos e incertezas do conhecimento científico e das problemáticas ambientais. Essa nova proposta também incide sobre a participação e o diálogo entre stakeholders como referência para ampliar a qualidade do saber científico e o entendimento da complexidade das questões ambientais. Este artigo discute a necessidade de se promover um salto epistemológico sobre a forma de pensar e produzir conhecimentos, bem como implementar a gestão dos riscos de desastres, tendo como objeto de estudo processos de comunicação e educação para prevenção de desastres.Studies on the risks of natural disasters have improved from a physicalist approach to a social and environmental perspective. However, planning and management still follow the anthropocentric paradigm of human superiority and the unlimited power of science and technology, evincing a cognitive, cultural and action inability on the part of experts, scientists and decision makers (or, rather, claim makers) to identify and act upon the social causes of risk production. In view of the Cartesian and Positivist science used to solve problems, based on security and on control over the natural world, a post-normal science has been proposed that considers the risks and uncertainties of scientific knowledge and environmental issues. This new approach encompasses participation and dialogue among stakeholders as a means to increase the quality of scientific knowledge and acknowledge the complexity of environmental issues. This article discusses the need for an epistemological leap on how we think and produce knowledge, as well as for implementing the management of disaster risk. Its objects of study are communication processes and education for disaster prevention

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease