Method for Assigning Priority Levels in Acute Care (MAPLe-AC) predicts outcomes of acute hospital care of older persons - a cross-national validation

To access publisher full text version of this article. Please click on the hyperlink in Additional Links field.BACKGROUND: Although numerous risk factors for adverse outcomes for older persons after an acute hospital stay have been : identified, a decision making tool combining all available information in a clinically meaningful way would be helpful for daily hospital practice. The purpose of this study was to evaluate the ability of the Method for Assigning Priority Levels for Acute Care (MAPLe-AC) to predict adverse outcomes in acute care for older people and to assess its usability as a decision making tool for discharge planning. METHODS: Data from a prospective multicenter study in five Nordic acute care hospitals with information from admission to a one year follow-up of older acute care patients were compared with a prospective study of acute care patients from admission to discharge in eight hospitals in Canada. The interRAI Acute Care assessment instrument (v1.1) was used for data collection. Data were collected during the first 24 hours in hospital, including pre-morbid and admission information, and at day 7 or at discharge, whichever came first. Based on this information a crosswalk was developed from the original MAPLe algorithm for home care settings to acute care (MAPLe-AC). The sample included persons 75 years or older who were admitted to acute internal medical services in one hospital in each of the five Nordic countries (n = 763) or to acute hospital care either internal medical or combined medical-surgical services in eight hospitals in Ontario, Canada (n = 393). The outcome measures considered were discharge to home, discharge to institution or death. Outcomes in a 1-year follow-up in the Nordic hospitals were: living at home, living in an institution or death, and survival. Logistic regression with ROC curves and Cox regression analyses were used in the analyses. RESULTS: Low and mild priority levels of MAPLe-AC predicted discharge home and high and very high priority levels predicted adverse outcome at discharge both in the Nordic and Canadian data sets, and one-year outcomes in the Nordic data set. The predictive accuracy (AUC's) of MAPLe-AC's was higher for discharge outcome than one year outcome, and for discharge home in Canadian hospitals but for adverse outcome in Nordic hospitals. High and very high priority levels in MAPLe-AC were also predictive of days to death adjusted for diagnoses in survival models. CONCLUSION: MAPLe-AC is a valid algorithm based on risk factors that predict outcomes of acute hospital care. It could be a helpful tool for early discharge planning although further testing for active use in clinical practice is still needed.Reykjavik Hospital Research Fund St. Joseph's Research Fund, Iceland Norwegian Medical Society 2 Diakonhjemmet Hospital Diakonhjemmet University College Diakonhjemmet Research Fund, Norway Sweden's Lions Fund, Sweden Health Transition Fund Health Canada Canadian Institutes for Health Research (CIHR) Nordic Lions Red Feather Fund Nordic Council of Ministers Roikjer Fund, Denmark Finnish Lions Fund, Finland Icelandic Lions Fund Memorial Fund of Helgu Jensdottur and Sigurliða Kristjanssona

Chromatic Illumination Discrimination Ability Reveals that Human Colour Constancy Is Optimised for Blue Daylight Illuminations

The phenomenon of colour constancy in human visual perception keeps surface colours constant, despite changes in their reflected light due to changing illumination. Although colour constancy has evolved under a constrained subset of illuminations, it is unknown whether its underlying mechanisms, thought to involve multiple components from retina to cortex, are optimised for particular environmental variations. Here we demonstrate a new method for investigating colour constancy using illumination matching in real scenes which, unlike previous methods using surface matching and simulated scenes, allows testing of multiple, real illuminations. We use real scenes consisting of solid familiar or unfamiliar objects against uniform or variegated backgrounds and compare discrimination performance for typical illuminations from the daylight chromaticity locus (approximately blue-yellow) and atypical spectra from an orthogonal locus (approximately red-green, at correlated colour temperature 6700 K), all produced in real time by a 10-channel LED illuminator. We find that discrimination of illumination changes is poorer along the daylight locus than the atypical locus, and is poorest particularly for bluer illumination changes, demonstrating conversely that surface colour constancy is best for blue daylight illuminations. Illumination discrimination is also enhanced, and therefore colour constancy diminished, for uniform backgrounds, irrespective of the object type. These results are not explained by statistical properties of the scene signal changes at the retinal level. We conclude that high-level mechanisms of colour constancy are biased for the blue daylight illuminations and variegated backgrounds to which the human visual system has typically been exposed

Spin-Imbalance in a One-Dimensional Fermi Gas

Superconductivity and magnetism generally do not coexist. Changing the relative number of up and down spin electrons disrupts the basic mechanism of superconductivity, where atoms of opposite momentum and spin form Cooper pairs. Nearly forty years ago Fulde and Ferrell and Larkin and Ovchinnikov proposed an exotic pairing mechanism (FFLO) where magnetism is accommodated by formation of pairs with finite momentum. Despite intense theoretical and experimental efforts, however, polarized superconductivity remains largely elusive. Here we report experimental measurements of density profiles of a two spin mixture of ultracold 6Li atoms trapped in an array of one dimensional (1D) tubes, a system analogous to electrons in 1D wires. At finite spin imbalance, the system phase separates with an inverted phase profile in comparison to the three-dimensional case. In 1D we find a partially polarized core surrounded by wings composed of either a completely paired BCS superfluid or a fully polarized Fermi gas, depending on the degree of polarization. Our observations are in quantitative agreement with theoretical calculations in which the partially polarized phase is found to be a 1D analogue of the FFLO state. This study demonstrates how ultracold atomic gases in 1D may be used to create non-trivial new phases of matter, and also paves the way for direct observation and further study of the FFLO phase.Comment: 30 pages, 7 figure

Varicella-Zoster viruses associated with post-herpetic neuralgia induce sodium current density increases in the ND7-23 Nav-1.8 neuroblastoma cell line

Post-herpetic neuralgia (PHN) is the most significant complication of herpes zoster caused by reactivation of latent Varicella-Zoster virus (VZV). We undertook a heterologous infection in vitro study to determine whether PHN-associated VZV isolates induce changes in sodium ion channel currents known to be associated with neuropathic pain. Twenty VZV isolates were studied blind from 11 PHN and 9 non-PHN subjects. Viruses were propagated in the MeWo cell line from which cell-free virus was harvested and applied to the ND7/23-Nav1.8 rat DRG x mouse neuroblastoma hybrid cell line which showed constitutive expression of the exogenous Nav 1.8, and endogenous expression of Nav 1.6 and Nav 1.7 genes all encoding sodium ion channels the dysregulation of which is associated with a range of neuropathic pain syndromes. After 72 hrs all three classes of VZV gene transcripts were detected in the absence of infectious virus. Single cell sodium ion channel recording was performed after 72 hr by voltage-clamping. PHN-associated VZV significantly increased sodium current amplitude in the cell line when compared with non-PHN VZV, wild-type (Dumas) or vaccine VZV strains ((POka, Merck and GSK). These sodium current increases were unaffected by acyclovir pre-treatment but were abolished by exposure to Tetrodotoxin (TTX) which blocks the TTX-sensitive fast Nav 1.6 and Nav 1.7 channels but not the TTX-resistant slow Nav 1.8 channel. PHN-associated VZV sodium current increases were therefore mediated in part by the Nav 1.6 and Nav 1.7 sodium ion channels. An additional observation was a modest increase in message levels of both Nav1.6 and Nav1.7 mRNA but not Nav 1.8 in PHN virally infected cells

Morphological characteristics of motor neurons do not determine their relative susceptibility to degeneration in a mouse model of severe spinal muscular atrophy

Spinal muscular atrophy (SMA) is a leading genetic cause of infant mortality, resulting primarily from the degeneration and loss of lower motor neurons. Studies using mouse models of SMA have revealed widespread heterogeneity in the susceptibility of individual motor neurons to neurodegeneration, but the underlying reasons remain unclear. Data from related motor neuron diseases, such as amyotrophic lateral sclerosis (ALS), suggest that morphological properties of motor neurons may regulate susceptibility: in ALS larger motor units innervating fast-twitch muscles degenerate first. We therefore set out to determine whether intrinsic morphological characteristics of motor neurons influenced their relative vulnerability to SMA. Motor neuron vulnerability was mapped across 10 muscle groups in SMA mice. Neither the position of the muscle in the body, nor the fibre type of the muscle innervated, influenced susceptibility. Morphological properties of vulnerable and disease-resistant motor neurons were then determined from single motor units reconstructed in Thy.1-YFP-H mice. None of the parameters we investigated in healthy young adult mice - including motor unit size, motor unit arbor length, branching patterns, motor endplate size, developmental pruning and numbers of terminal Schwann cells at neuromuscular junctions - correlated with vulnerability. We conclude that morphological characteristics of motor neurons are not a major determinant of disease-susceptibility in SMA, in stark contrast to related forms of motor neuron disease such as ALS. This suggests that subtle molecular differences between motor neurons, or extrinsic factors arising from other cell types, are more likely to determine relative susceptibility in SMA

Intra-cluster correlation coefficients in adults with diabetes in primary care practices: the Vermont Diabetes Information System field survey

BACKGROUND: Proper estimation of sample size requirements for cluster-based studies requires estimates of the intra-cluster correlation coefficient (ICC) for the variables of interest. METHODS: We calculated the ICC for 112 variables measured as part of the Vermont Diabetes Information System, a cluster-randomized study of adults with diabetes from 73 primary care practices (the clusters) in Vermont and surrounding areas. RESULTS: ICCs varied widely around a median value of 0.0185 (Inter-quartile range: 0.006, 0.037). Some characteristics (such as the proportion having a recent creatinine measurement) were highly associated with the practice (ICC = 0.288), while others (prevalence of some comorbidities and complications and certain aspects of quality of life) varied much more across patients with only small correlation within practices (ICC<0.001). CONCLUSION: The ICC values reported here may be useful in designing future studies that use clustered sampling from primary care practices

MutLα heterodimers modify the molecular phenotype of Friedreich ataxia

This article has been made available through the Brunel Open Access Publishing Fund.Background: Friedreich ataxia (FRDA), the most common autosomal recessive ataxia disorder, is caused by a dynamic GAA repeat expansion mutation within intron 1 of FXN gene, resulting in down-regulation of frataxin expression. Studies of cell and mouse models have revealed a role for the mismatch repair (MMR) MutS-heterodimer complexes and the PMS2 component of the MutLα complex in the dynamics of intergenerational and somatic GAA repeat expansions: MSH2, MSH3 and MSH6 promote GAA repeat expansions, while PMS2 inhibits GAA repeat expansions. Methodology/Principal Findings: To determine the potential role of the other component of the MutLα complex, MLH1, in GAA repeat instability in FRDA, we have analyzed intergenerational and somatic GAA repeat expansions from FXN transgenic mice that have been crossed with Mlh1 deficient mice. We find that loss of Mlh1 activity reduces both intergenerational and somatic GAA repeat expansions. However, we also find that loss of either Mlh1 or Pms2 reduces FXN transcription, suggesting different mechanisms of action for Mlh1 and Pms2 on GAA repeat expansion dynamics and regulation of FXN transcription. Conclusions/Significance: Both MutLα components, PMS2 and MLH1, have now been shown to modify the molecular phenotype of FRDA. We propose that upregulation of MLH1 or PMS2 could be potential FRDA therapeutic approaches to increase FXN transcription. © 2014 Ezzatizadeh et al.This article has been made available through the Brunel Open Access Publishing Fund

Outcomes of decompression for lumbar spinal canal stenosis based upon preoperative radiographic severity

BACKGROUND: The relationship between severity of preoperative radiographic findings and surgical outcomes following decompression for lumbar degenerative spinal canal stenosis is unclear. Our aim in this paper was to gain insight into this relationship. We determined pre-operative radiographic severity on MRI scans using strict methodological controls and correlated such severity with post-operative outcomes using prospectively collected data. METHODS: Twenty-seven consecutive patients undergoing decompression for isolated degenerative spinal canal stenosis at L4-L5 were included. We measured cross-sectional area on MRI using the technique of Hamanishi. We categorized the severity of stenosis using Laurencin and Lipson's 'Stenosis Ratio'. We determined pre-operative status (prospectively) and post-operative outcomes using Weiner and Fraser's 'Neurogenic Claudication Outcome Score'. We determined patient satisfaction using standardized questionnaires. Each of these is a validated measure. Formal statistical evaluation was undertaken. RESULTS: No patients (0 of 14) with a greater than 50% reduction in cross-sectional area on pre-operative MRI had unsatisfactory outcomes. In contrast, outcomes for patients with less than or equal to 50% reduction in cross-sectional area had unsatifactory outcomes in 6 of 13 cases, with all but one negative outcome having a cross-sectional area reduction between 32% and 47%. CONCLUSION: The findings suggest that there appears to be a relationship between severity of stenosis and outcomes of decompressive surgery such that patients with a greater than 50% reduction in cross sectional area are more likely to have a successful outcome

Cerebrospinal fluid levels of opioid peptides in fibromyalgia and chronic low back pain

BACKGROUND: The mechanism(s) of nociceptive dysfunction and potential roles of opioid neurotransmitters are unresolved in the chronic pain syndromes of fibromyalgia and chronic low back pain. METHODS: History and physical examinations, tender point examinations, and questionnaires were used to identify 14 fibromyalgia, 10 chronic low back pain and 6 normal control subjects. Lumbar punctures were performed. Met-enkephalin-Arg(6)-Phe(7 )(MEAP) and nociceptin immunoreactive materials were measured in the cerebrospinal fluid by radioimmunoassays. RESULTS: Fibromyalgia (117.6 pg/ml; 85.9 to 149.4; mean, 95% C.I.; p = 0.009) and low back pain (92.3 pg/ml; 56.9 to 127.7; p = 0.049) groups had significantly higher MEAP than the normal control group (35.7 pg/ml; 15.0 to 56.5). MEAP was inversely correlated to systemic pain thresholds. Nociceptin was not different between groups. Systemic Complaints questionnaire responses were significantly ranked as fibromyalgia > back pain > normal. SF-36 domains demonstrated severe disability for the low back pain group, intermediate results in fibromyalgia, and high function in the normal group. CONCLUSIONS: Fibromyalgia was distinguished by higher cerebrospinal fluid MEAP, systemic complaints, and manual tender points; intermediate SF-36 scores; and lower pain thresholds compared to the low back pain and normal groups. MEAP and systemic pain thresholds were inversely correlated in low back pain subjects. Central nervous system opioid dysfunction may contribute to pain in fibromyalgia

Attitudes of US medical trainees towards neurology education: "Neurophobia" - a global issue

<p>Abstract</p> <p>Background</p> <p>Several studies in the United Kingdom and Asia have suggested that medical students and residents have particular difficulty in diagnosing and managing patients with neurological problems. Little recent information is available for US trainees. We examined whether students and residents at a US university have difficulty in dealing with patients with neurological problems, identified the perceived sources of these difficulties and provide suggestions for the development of an effective educational experience in neurology.</p> <p>Methods</p> <p>A questionnaire was administered to third and fourth year medical students at a US school of medicine and to residents of an internal medicine residency program affiliated with that school. Perceived difficulties with eight medical specialties, including neurology, were examined. Methods considered to be most useful for learning medicine were documented. Reasons why neurology is perceived as difficult and ways to improve neurological teaching were assessed.</p> <p>Results</p> <p>152 surveys were completed. Participation rates varied, with medical students having higher response rates (> 50%) than medical residents (27%-48%). Respondents felt that neurology was the medical specialty they had least knowledge in (p < 0.001) and was most difficult (p < 0.001). Trainees also felt they had the least confidence when dealing with patients with neurological complaints (p < 0.001). Residents felt more competent in neurology than students (p < 0.001). The paramount reasons for perceived difficulties with neurology were the complexity of neuroanatomy, limited patient exposure and insufficient teaching. Transition from pre-clinical to clinical medicine led to a doubling of "poor" ratings for neurological teaching. Over 80% of the respondents felt that neurology teaching could be improved through greater exposure to patients and more bedside tutorials.</p> <p>Conclusions</p> <p>Medical students and residents at this US medical university found neurology difficult. Although this is consistent with prior reports from Europe and Asia, studies in other universities are needed to confirm generalizability of these findings. The optimal opportunity for improvement is during the transition from preclinical to clinical years. Enhanced integration of basic neurosciences and clinical neurology with emphasis on increased bedside tutorials and patient exposure should improve teaching. Studies are needed to quantify the effect of these interventions on confidence of trainees when dealing with patients presenting with neurological complaints.</p