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.
Aims Widowed people have increased mortality compared to married people of the same age. Although most widowed people are of older age, few studies include the oldest old. As life expectancy is increasing, knowledge of widowhood into older age is needed. This study aimed to examine mortality and widowhood in older age by comparing mortality in widowed and married people by sex, age, time since spousal loss and cause of death. Methods A Danish register-based matched cohort study of 10% of widowed persons ⩾65 years in the years 2000–2009. For each randomly drawn widowed person, five married persons were matched on sex and age. Mortality rate ratios (MRR) were calculated using Poisson regression, and stratified according to sex and 5-year age intervals. MRRs were furthermore calculated by time since spousal loss and by specific cause of death. Results The study included 82 130 persons contributing with 642 914.8 person-years. The overall MRR between widowed and married persons with up to 16 years of follow-up was 1.25 (95% CI 1.23–1.28). At age ⩾95 years for men, and ⩾90 years for women, no differences in mortality rates were seen between widowed and married persons. Mortality in widowed persons was increased for most specific causes of death, with the highest MRR from external causes (MRR 1.53 [1.35–1.74]) and endocrine diseases (MRR 1.51 [1.34–1.70]). Conclusions Widowhood was associated with increased mortality in older age for both men and women until age ⩾95 and ⩾90 years, respectively. Increased mortality was observed for almost all causes of death.
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