Background: Accurate and timely diagnosis of Alzheimer’s disease (AD) is important for prompt initiation of treatment in patients with AD and to avoid inappropriate treatment of patients with false-positive diagnoses. Methods: Using a Markov model, we estimated the lifetime costs and quality-adjusted life-years (QALYs) of cerebrospinal fluid biomarker analysis in a cohort of patients referred to a neurologist or memory clinic with suspected AD who remained without a definitive diagnosis of AD or another condition after neuroimaging. Parametric values were estimated from previous health economic models and the medical literature. Extensive deterministic and probabilistic sensitivity analyses were performed to evaluate the robustness of the results. Results: At a 12.7% pretest probability of AD, biomarker analysis after normal neuroimaging findings has an incremental cost-effectiveness ratio (ICER) of $11,032 per QALY gained. Results were sensitive to the pretest prevalence of AD, and the ICER increased to over $50,000 per QALY when the prevalence of AD fell below 9%. Results were also sensitive to patient age (biomarkers are less cost-effective in older cohorts), treatment uptake and adherence, biomarker test characteristics, and the degree to which patients with suspected AD who do not have AD benefit from AD treatment when they are falsely diagnosed. Conclusions: The cost-effectiveness of biomarker analysis depends critically on the prevalence of AD in the tested population. In general practice, where the prevalence of AD after clinical assessment and normal neuroimaging findings may be low, biomarker analysis is unlikely to be cost-effective at a willingness-to-pay threshold of $50,000 per QALY gained. However, when at least 1 in 11 patients has AD after normal neuroimaging findings, biomarker analysis is likely cost-effective. Specifically, for patients referred to memory clinics with memory impairment who do not present neuroimaging evidence of medial temporal lobe atrophy, pretest prevalence of AD may exceed 15%. Biomarker analysis is a potentially cost-saving diagnostic method and should be considered for adoption in high-prevalence centers.
The articles in this issue of the journal cover a wide range of conflict intervention approaches and demonstrate the reflective, thoughtful and energetic exploration of their work by practitioners in the field. Whatling explores approaches to working with high conflict, a challenging practice for many mediators. During a conflict, defensive decision-making reinforces high conflict, so that the mediator must do as much as possible to defuse this defensiveness in order to assist the parties in making their own decisions. As well as offering many practice principles for a constructive mediation conversation, Whatling urges practitioners to be mindful and hold a constant internal reflexive dialogue. These, he holds, are crucial in working with those in high conflict.
There is mixed evidence from correlational studies that breastfeeding impacts children's development. Propensity score matching with large samples can be an effective tool to remove potential bias from observed confounders in correlational studies. The aim of this study was to investigate the impact of breastfeeding on children's cognitive and noncognitive development at 3 and 5 years of age. Participants included ∼8000 families from the Growing Up in Ireland longitudinal infant cohort, who were identified from the Child Benefit Register and randomly selected to participate. Parent and teacher reports and standardized assessments were used to collect information on children's problem behaviors, expressive vocabulary, and cognitive abilities at age 3 and 5 years. Breastfeeding information was collected via maternal report. Propensity score matching was used to compare the average treatment effects on those who were breastfed. Before matching, breastfeeding was associated with better development on almost every outcome. After matching and adjustment for multiple testing, only 1 of the 13 outcomes remained statistically significant: children's hyperactivity (difference score, -0.84; 95% confidence interval, -1.33 to -0.35) at age 3 years for children who were breastfed for at least 6 months. No statistically significant differences were observed postmatching on any outcome at age 5 years. Although 1 positive benefit of breastfeeding was found by using propensity score matching, the effect size was modest in practical terms. No support was found for statistically significant gains at age 5 years, suggesting that the earlier observed benefit from breastfeeding may not be maintained once children enter school.
OBJECTIVE Currently, little is known about the biomechanics of head impact for concussion in youths (ages 5 to 18 years). Even less is known about the biomechanical characteristics and variables related to head impacts that may be useful in differentiating between transient and persistent postconcussion symptoms in a youth population. The purpose of this research was to examine the differences in biomechanics of youth head impact for transient postconcussion symptoms (TPCSs) and persistent postconcussion symptoms (PPCSs) by using data from a hospital population. METHODS In a laboratory setting and using physical, computational, and finite element models, the authors reconstructed falling events in a large cohort of patients who had sustained a brain injury that resulted in transient or persistent postconcussion symptoms. The falling events and resulting concussions for the TPCS and PPCS patient groups were analyzed in terms of force, energy, peak resultant linear and rotational accelerations, and maximum principal strain in the gray and white matter of the brain, as well as measurements of cumulative strain damage. RESULTS The results indicated that there were no significant differences between the groups for any of the variables analyzed. CONCLUSIONS With methods derived for use in an adult population, the magnitudes of peak linear acceleration for the youth data set were determined to be above the 50% risk of injury. The youth data set showed higher brain tissue strain responses for lower energy and impact velocities than measured in adults, suggesting that youths are at higher risk of concussive injury at lower event severities. A trend shown by some variables indicated that larger magnitudes of response were associated with PPCSs, but no single measurement variable consistently differentiated between the TPCS and PPCS groups. It is possible that using the biomechanics of head and brain responses to predict a subjective symptom load may not be appropriate. To enhance future biomechanical analyses, further investigations should include the use of quantifiable measures of brain injury linked to clinical outcomes and possible confounding factors such as history of brain injury and patient predisposition.
Trophoblastic cell lines are widely used in in vitro studies of placental function as a surrogate for primary trophoblasts. To date, no reference proteomics dataset exists to directly compare the shared and unique characteristics of these cells. Here, we performed comparative proteomic profiling of the BeWo and HTR8/SVneo cell lines using label-free quantitative mass spectrometry. 1557 proteins were identified, which included 338 uniquely attributed to BeWo cells, and a further 304 specifically identified in HTR8/SVneo cells. Raw data is available via ProteomeXchange, identifier PDX005045. Of the 915 proteins expressed by both cell lines, 105 were of higher abundance in BeWo cells, while 199 proteins had a significantly higher expression in HTR8/SVneo cells. Comparative gene ontology of unique and up-regulated proteins revealed principal differences in cell junction/adhesion, catenin complex, spindle and microtubule associated complex, as well as cell differentiation. Our data indicates that BeWo cells express an epithelial proteome more characteristic of villous trophoblasts, whereas HTR8/SVneo cells embrace a mesenchymal phenotype, more characteristic of extravillous trophoblasts. This novel comparative proteomic profiling of these trophoblastic cell lines provides a useful platform for future investigations of placental function. This article is protected by copyright. All rights reserved.
This review examines the effect of a dual-task on the gait parameters of older adults with a mean gait speed of 1.0m/s or greater, and the effect of type and complexity of task. A systematic review of Web of Science, PubMed, SCOPUS, Embase and psychINFO was performed in July 2016. Twenty-three studies (twenty-eight data sets) were reviewed and pooled for meta-analysis. The effect size on seven gait parameters was measured as the raw mean difference between single and dual-task performance. Gait speed significantly reduced with the addition of a dual-task, with increasing complexity showing greater decrements. Cadence, stride time and measures of gait variability were all negatively affected under the dual-task condition. In older adults, the addition of a dual-task significantly reduces gait speed and cadence, with possible implications for the assessment of older people, as the addition of a dual-task may expose deficits not observed under single-task assessment.