RESUMEN
Neurodevelopmental disorders - including attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder, communication disorders, intellectual disability, motor disorders, specific learning disorders, and tic disorders - manifest themselves early in development. Valid, reliable and broadly usable biomarkers supporting a timely diagnosis of these disorders would be highly relevant from a clinical and public health standpoint. We conducted the first systematic review of studies on candidate diagnostic biomarkers for these disorders in children and adolescents. We searched Medline and Embase + Embase Classic with terms relating to biomarkers until April 6, 2022, and conducted additional targeted searches for genome-wide association studies (GWAS) and neuroimaging or neurophysiological studies carried out by international consortia. We considered a candidate biomarker as promising if it was reported in at least two independent studies providing evidence of sensitivity and specificity of at least 80%. After screening 10,625 references, we retained 780 studies (374 biochemical, 203 neuroimaging, 133 neurophysiological and 65 neuropsychological studies, and five GWAS), including a total of approximately 120,000 cases and 176,000 controls. While the majority of the studies focused simply on associations, we could not find any biomarker for which there was evidence - from two or more studies from independent research groups, with results going into the same direction - of specificity and sensitivity of at least 80%. Other important metrics to assess the validity of a candidate biomarker, such as positive predictive value and negative predictive value, were infrequently reported. Limitations of the currently available studies include mostly small sample size, heterogeneous approaches and candidate biomarker targets, undue focus on single instead of joint biomarker signatures, and incomplete accounting for potential confounding factors. Future multivariable and multi-level approaches may be best suited to find valid candidate biomarkers, which will then need to be validated in external, independent samples and then, importantly, tested in terms of feasibility and cost-effectiveness, before they can be implemented in daily clinical practice.
RESUMEN
Purpose: Becoming widowed is a stressful health-threatening event causing major life changes. We explored how widowed people experience becoming widowed and examined if these experiences are quantitatively associated with widowhood. Methods: A multi-methods study using an exploratory sequential mixed-methods approach including a qualitative descriptive study with widowed people from Denmark and a Swedish cohort study. Qualitative interviews (n = 9) were analysed using qualitative content analysis, describing experiences as explained by the widowed people. The quantitative association of the experiences was examined by identifying proxies for the qualitative experiences of widowhood in the cohort study and examining the occurrence in widowed people compared to married people (n = 1,095). Results: Six categories of experiences emerged: the circumstances around spousal death, mental health and well-being, physical health, social relations, activities and practicalities. The quantitative examination showed a significant association with widowhood regarding mental and physical health problems. Conclusion: The circumstances around spousal death and the time before spousal death, in general, were important to how participants felt being widowed. Being ill negatively affected mental health and well-being, partly because of the inability to participate in activities and social relations. This is important, as health problems are more common among widowed people than married people.
