Surgical adverse outcome reporting as part of routine clinical care

Analysis and support of clinical decision makin

Age Differentiation within Gray Matter, White Matter, and between Memory and White Matter in an Adult Life Span Cohort.

It is well established that brain structures and cognitive functions change across the life span. A long-standing hypothesis called "age differentiation" additionally posits that the relations between cognitive functions also change with age. To date, however, evidence for age-related differentiation is mixed, and no study has examined differentiation of the relationship between brain and cognition. Here we use multigroup structural equation models (SEMs) and SEM trees to study differences within and between brain and cognition across the adult life span (18-88 years) in a large (N > 646, closely matched across sexes), population-derived sample of healthy human adults from the Cambridge Centre for Ageing and Neuroscience (www.cam-can.org). After factor analyses of gray matter volume (from T1- and T2-weighted MRI) and white matter organization (fractional anisotropy from diffusion-weighted MRI), we found evidence for the differentiation of gray and white matter, such that the covariance between brain factors decreased with age. However, we found no evidence for age differentiation among fluid intelligence, language, and memory, suggesting a relatively stable covariance pattern among cognitive factors. Finally, we observed a specific pattern of age differentiation between brain and cognitive factors, such that a white matter factor, which loaded most strongly on the hippocampal cingulum, became less correlated with memory performance in later life. These patterns are compatible with the reorganization of cognitive functions in the face of neural decline, and/or with the emergence of specific subpopulations in old age.SIGNIFICANCE STATEMENT The theory of age differentiation posits age-related changes in the relationships among cognitive domains, either weakening (differentiation) or strengthening (dedifferentiation), but evidence for this hypothesis is mixed. Using age-varying covariance models in a large cross-sectional adult life span sample, we found age-related reductions in the covariance among both brain measures (neural differentiation), but no covariance change among cognitive factors of fluid intelligence, language, and memory. We also observed evidence of uncoupling (differentiation) between a white matter factor and cognitive factors in older age, most strongly for memory. Together, our findings support age-related differentiation as a complex, multifaceted pattern that differs for brain and cognition, and discuss several mechanisms that might explain the changing relationship between brain and cognition

Challenges and Solutions to the Measurement of Neurocognitive Mechanisms in Developmental Settings

Identifying early neurocognitive mechanisms that confer risk for mental health problems is one important avenue as we seek to develop successful early interventions. Currently, however, we have limited understanding of the neurocognitive mechanisms involved in shaping mental health trajectories from childhood through young adulthood, and this constrains our ability to develop effective clinical interventions. In particular, there is an urgent need to develop more sensitive, reliable, and scalable measures of individual differences for use in developmental settings. In this review, we outline methodological shortcomings that explain why widely used task-based measures of neurocognition currently tell us little about mental health risk. We discuss specific challenges that arise when studying neurocognitive mechanisms in developmental settings, and we share suggestions for overcoming them. We also propose a novel experimental approach—which we refer to as “cognitive microscopy”—that involves adaptive design optimization, temporally sensitive task administration, and multilevel modeling. This approach addresses some of the methodological shortcomings outlined above and provides measures of stability, variability, and developmental change in neurocognitive mechanisms within a multivariate framework

An amino acid polymorphism in histidine-rich glycoprotein (HRG) explains 59% of the variance in plasma HRG levels

A pedigree-based maximum likelihood method developed by Lange et al. (12) was used to study the contribution of a newly defined di-allelic polymorphism in histidine-rich glycoprotein (HRG) to the plasma levels of HRG. In four families (n = 99) and 20 volunteers we found a heritability of 70%, an age effect of 3% and an effect of individual environmental factors of 27%. These results are remarkably similar to the results found in a previous parent-twin study in which a heritability of 69% and an effect of random environment of 31% was found. The overall genetic influence in the present study can be subdivided into an effect of 59% by the HRG phenotype and 11% by residual genetic factors. The influence of the HRG phenotype of 59% can entirely be explained by adding up the effect of the two alleles that make up the phenotype. These results indicate a codominant inheritance pattern of HRG levels in which the genetic influence can almost completely be ascribed to the additive effect of the di-allelic HRG locus whereas only a small part is due to other loci

Follow-up of colorectal cancer patients: quality of life and attitudes towards follow-up.

The aims of our study were to assess the effect of follow-up on the quality of life of colorectal cancer patients and to assess the attitudes of patients towards follow-up as a function of patient characteristics. Patients who had been treated with curative intent were selected from four types of hospitals. Eighty-two patients were interviewed using a structured questionnaire, whereas 130 patients received the questionnaire by mail. To assess the effect of follow-up on the quality of life, the interviewed patients were randomly allocated to three groups and interviewed at different times in relation to the follow-up visit. Analysis did not show an effect of the follow-up visit on quality of life. Patients reported a positive attitude towards follow-up: it reassured them, they judged the communication with the physician to be positive, and they experienced only slight nervous anticipation and few other disadvantages. Patients reported a strong preference for follow-up, and a large majority would prefer follow-up even if it would not lead to earlier detection of a recurrence. Apart from living situation, no patient characteristics were clearly associated with the attitude towards follow-up. Implications for clinical practice are discussed

The potential of individualized dosing of ravulizumab to improve patient-friendliness of paroxysmal nocturnal haemoglobinuria treatment at reduced costs

Contains fulltext : 237767.pdf (Publisher’s version ) (Open Access)Ravulizumab is a very expensive complement C5-inhibitor for the treatment of paroxysmal nocturnal haemoglobinuria, with a fixed-dosing interval of 8 weeks. For lifelong treatment, a cost-effective and patient-friendly dosing strategy is preferred. We therefore explored alternative ravulizumab dosing regimens in silico based on the thorough dose-finding studies of the manufacturer. Extending the interval to 10 weeks or individually extending the interval to a mean of 12.8 weeks based on pharmacokinetic monitoring resulted in noninferior efficacy in terms of lactate dehydrogenase normalization, with drug cost savings up to 37%. We here show the potential of individualized ravulizumab dosing to improve patient-friendliness at reduced costs