Altered performance of reelin-receptor ApoER2 deficient mice on spatial tasks using the Barnes maze

The apolipoprotein E receptor 2 (ApoER2), expressed predominantly in forebrain regions including the hippocampus, is 1 of 2 receptors for the extracellular matrix protein reelin, which is critical for cortical development. Previous studies of ApoER2 mutant mice have indicated deficits in synaptic plasticity and learning. The current authors assessed learning and memory of ApoER2 knockout and wild-type mice on the Barnes circular maze. Mice were trained in this task for 22 days, followed by memory recall and reversal tests. ApoER2 knockout mice were initially slower to complete the task, but by Day 22 they were more accurate than wild-type mice on several indices. There were no differences in memory assessed by the recall task, but ApoER2 knockout mice performed significantly worse on the memory reversal task. ApoER2 knockout mice also displayed altered use of specific search strategies and relationship of these strategies to errors made on the maze.     

Implementation of a metastatic malignancy of unknown primary origin service led by a palliative physician

Background: Cancer of unknown primary is the fourth most common cause of cancer death in the United Kingdom. National guidance in 2010 recommended the establishment of a dedicated unknown primary team to facilitate targeted investigation and symptom control. A service development project was undertaken to identify those affected by malignancy of unknown origin and institute a pathway for coordinating their care led by a palliative physician.

Method: In order to describe the patient population and illness trajectory and to assess the effect of the new pathway on the clinical outcomes we used a retrospective and prospective comparative case notes survey to identify the pre- and post-pathway population. This took place in secondary care. Inclusion criteria were patients with metastatic disease with no known primary; exclusion criteria were where the site of metastasis was so suggestive of a primary that it would be managed as per that disease process. 88 patients were included.Results: Mean age was 72.5 years. The mean survival time from presentation was 81.8 days. There was no difference pre or during pathway implementation in age, performance status or survival time. There was no reduction in the numbers referred for tumour directed therapy. There was a non-statistically significant reduction in the number who died in hospital during the pathway implementation.

Conclusions: This study suggests having a metastatic malignancy of unknown primary origin service led by a palliative physician does not reduce the number referred for tumour directed therapy. It also adds evidence of the poor prognosis and thus the need for early palliative care input.     

Association Between Whole-Body Vibration and Low-Back Disorders in Farmers: A Scoping Review

Introduction: Low-back disorders (LBDs) are the most common musculoskeletal problem among farmers, with higher prevalence rates than in other occupations. Farmers who operate tractors and other types of machinery can have substantial exposure to whole-body vibration (WBV). Although there appears to be an association between LBDs and WBV, the causal relationship is not clear. Objective: This scoping review investigates the association between WBV and LBDs specifically among farmers. Methods: Nine databases were searched using groups of terms for two concepts: ‘farming’ and ‘low back disorder’. Screening, data extraction, and quality assessment were performed by two reviewers independently. Included studies met the following criteria: focused on adult farmers/agricultural workers; assessed exposure to operating farm machinery such tractor, combine, or all-terrain vehicle; assessed LBDs as an outcome; and reported an inferential test to assess the relationship between WBV and LBD. Results: After 276 full texts screened, 11 articles were found to analyze WBV as a risk factor for LBDs. Three were case–control, five cross-sectional, and three retrospective cohorts. Four studies showed no association between WBV and LBDs, four a positive association, and three results were mixed depending on the exposure/outcome measure. Conclusion: A firm conclusion is difficult due to heterogeneity in, LBDs definition, type of farm commodity, study design, and statistical strategy. Direct comparisons and synthesis were not possible. Although retrospective cohort studies tended to show a relationship, future studies with a prospective cohort design could help clarify this association further.     

A new risk prediction model for critical care: the Intensive Care National Audit & Research Centre (ICNARC) model

OBJECTIVE: To develop a new model to improve risk prediction for admissions to adult critical care units in the UK. DESIGN: Prospective cohort study. SETTING: The setting was 163 adult, general critical care units in England, Wales, and Northern Ireland, December 1995 to August 2003. PATIENTS: Patients were 216,626 critical care admissions. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The performance of different approaches to modeling physiologic measurements was evaluated, and the best methods were selected to produce a new physiology score. This physiology score was combined with other information relating to the critical care admission-age, diagnostic category, source of admission, and cardiopulmonary resuscitation before admission-to develop a risk prediction model. Modeling interactions between diagnostic category and physiology score enabled the inclusion of groups of admissions that are frequently excluded from risk prediction models. The new model showed good discrimination (mean c index 0.870) and fit (mean Shapiro's R 0.665, mean Brier's score 0.132) in 200 repeated validation samples and performed well when compared with recalibrated versions of existing published risk prediction models in the cohort of patients eligible for all models. The hypothesis of perfect fit was rejected for all models, including the Intensive Care National Audit & Research Centre (ICNARC) model, as is to be expected in such a large cohort. CONCLUSIONS: The ICNARC model demonstrated better discrimination and overall fit than existing risk prediction models, even following recalibration of these models. We recommend it be used to replace previously published models for risk adjustment in the UK.