Regional nerve blockade for early analgesic management of elderly patients with hip fracture - a narrative review.

Elderly patients with hip fracture experience high morbidity and mortality, and are often undertreated for pain. Acute pain management in the elderly is challenging, with physiological frailty, medical comorbidities and cognitive impairment commonly compounding pain assessment and treatment. Guidelines outlining current best practice for acute pain management in the elderly now exist, but evidence suggests that practice remains variable and there continues to be scope for improvement. We conducted a narrative review of the literature to examine the challenges of acute pain management in the elderly, and to evaluate evidence for the role of regional nerve blocks for acute pain associated with hip fracture in the elderly. There is consistent evidence that regional nerve blocks can effectively reduce pain associated with hip fracture, providing rapid-onset, site-specific analgesia that is more effective than standard systemic analgesia alone. There is also moderate evidence that nerve blocks may contribute to reduced rates of delirium, and some suggestion of reduced length of inpatient stay, morbidity and mortality, although limited evidence is available. Fascia iliaca blocks are emerging as a block of choice, with evidence they can be safely and rapidly administered under ultrasound guidance in the acute setting, by both trained medical and nursing staff, with good effect. Ideally, comprehensive pain protocols for elderly hip fracture patients are required, that integrate evidence-based fascia iliaca block use, timely and repeated pain assessment, and multidisciplinary orthogeriatric patient care.

The ROARI project - Road Accident Acute Rehabilitation Initiative: a randomised clinical trial of two targeted early interventions for road-related trauma.

OBJECTIVES: To determine the effectiveness of an Early Rehabilitation Intervention (ERI ) versus a Brief Education Intervention (BEI) following road trauma. PRIMARY OBJECTIVE: return to work or usual activities at 12 weeks (for minor/moderate injury) and 24 weeks for major injury. SECONDARY OBJECTIVES: Reduction in pain, anxiety, depression, disability and incidence of Post Traumatic Stress Disorder and improved quality of life. DESIGN: A multi-site single-blinded stratified randomized clinical trial (RCT). METHODS: 184 patients (92 in each arm) were recruited over 18 months and followed for 12 weeks (minor/moderate injury) and 24 weeks (major injury). Screening questionnaires at 2-4 weeks and follow-up interviews by phone for all outcome measures were undertaken. For those in the ERI group with a positive screen for high risk of persistent symptoms, an early assessment and intervention by a Rehabilitation Physician was offered. Those in the BEI group were sent written information and advised to see their GP. RESULTS: 89.4% of injuries were mild in this cohort. At 12 weeks 73.8% and 69.1% of patients in the ERI and the BEI groups respectively had returned to work or usual activities. There were no significant differences between the two intervention groups with respect to the primary or any secondary outcome measures. CONCLUSION: This is the first RCT of an ERI following road trauma in Australia. A targeted ERI is as effective as a BEI in assisting those with mild/moderate trauma to return to work or usual activities.

Perceptions and attitudes of rehabilitation medicine physicians on complementary and alternative medicine in Australia.

BACKGROUND: The growing demand for complementary and alternative medicine (CAM) is undeniable. We report a first study about the attitudes and behaviour of Australian rehabilitation physicians to CAM. METHODS: A prospective cross-sectional survey was undertaken to document the prevalence of, knowledge about and referrals to CAM therapies and their perceived effectiveness, by a sample of Australian rehabilitation physicians. RESULTS: Thirty-six out of 94 actively practising rehabilitation physicians from the Australasian Faculty of Rehabilitation Medicine, the Royal Australasian College of Physicians, replied to the survey, a response rate of 38%, and 85% reported familiarity with CAM, the most familiar therapies being acupuncture (80%), yoga (74%) and Tai-Chi (72%). CAM referral was reported in 84%, 38% personally used CAM, 94% of patients enquired about CAM therapies, 32% of respondents routinely enquired about CAM use. Age, sex and year of Fellowship were not associated with familiarity, personal use or frequency of patient enquiry about CAM. Those who reported to be very familiar with CAM were more likely to routinely enquire about CAM use (P = 0.028) and be more confident in prescribing certain CAM therapies (P < 0.05). CONCLUSION: Australian rehabilitation physicians report similar CAM referral rates to Canadian physiatrists and Australian general practitioners. The most commonly prescribed therapies were acupuncture, yoga and Tai-Chi. Almost all patients use CAM therapies, but only a minority of rehabilitation physicians enquires about CAM use on a regular basis. The latter may avoid potentially harmful drug interactions, as well as improve the quality of the physician-patient relationship.

Stroke rehab down under: can Rupert Murdoch, Crocodile Dundee, and an Aboriginal elder expect the same services and care?

Australia is the world's sixth largest country, has a relatively small population of 21.5 million, and a blended (public and private) health system. In this article, we explain the stroke rehabilitation infrastructure including consumer organisations, research networks, data collection systems, and registries. This represents a complex but fledgling set of organisations showing great promise for coordination of care and research. The article goes on to expose the inequalities in service provision by describing the paths of stroke survivors in three settings - in the city, in the country, and in remote settings. The complexities and difficulties in treating indigenous stroke survivors are described in a culturally sensitive narrative. The article then discusses the outcomes of the first Australian audit of post acute stroke services completed in December 2008, which describes the journeys of 2,119 stroke survivors at 68 rehabilitation units throughout Australia's 6 states and 2 territories. It demonstrates an average length of stay of 26 days, with 18% of survivors requiring nursing home or other supported accommodation. The article concludes with future directions for stroke rehabilitation in Australia, which include hyperacute rehabilitation trials, studies in 7-days-a-week rehabilitation, and the potential use of robotics.

A prospective controlled study in the prevalence of posttraumatic headache following mild traumatic brain injury.

OBJECTIVE: To establish the prevalence of post traumatic headache, persisting at 3 months following minor traumatic brain injury. DESIGN: A prospective controlled study of patients admitted with a diagnosis of mild traumatic brain injury and matched orthopedic controls over 12 months during 2004. SETTING: A level two inner city Emergency Department in Sydney, Australia. PATIENTS: One hundred eligible sequential admissions with mild traumatic brain injury as defined by American Congress of Rehabilitation Medicine, 1993, and 100 matched minor injury controls with nondeceleration injuries. INTERVENTIONS: Subjects were part of a study on prediction of postconcussive syndrome and had neuropsychological tests, balance test and pain recordings taken at the time of injury, at 1 month and at 3 months post injury. OUTCOME MEASURES: Main measures were the reporting of headache "worse than prior to the injury" and concordant with the definition of Posttraumatic Headache according to International Headache Society Classification of Headache Disorders 2003. RESULTS: 15.34% of those with minor head injury continued to complain of perisistant posttraumatic headache at 3 months compared to 2.2% of the minor injury controls. CONCLUSIONS: To the authors' knowledge this is the first controlled prospective study in the prevalence of posttraumatic headache following mild traumatic brain injury.

Asbestos increases mammalian AP-endonuclease gene expression, protein levels, and enzyme activity in mesothelial cells.

Only two DNA repair enzymes, DNA polymerase beta and O6-methylguanine-DNA methyltransferase, have been shown to be inducible in mammalian cells by genotoxic agents. We show here that crocidolite asbestos induces the DNA repair enzyme, apurinic/apyrimidinic (AP)-endonuclease, in isolated mesothelial cells, the progenitor cells of malignant mesothelioma. Asbestos at nontoxic concentrations of 1.25 and 2.5 microg/cm2 significantly increased AP-endonuclease mRNA and protein levels as well as enzyme activity (P < 0.05) in a dose-dependent manner in rat pleural mesothelial cells. These increases were persistent from 24 to 72 h after initial exposure to fibers. Changes were not observed with glass beads, a noncarcinogenic particle. Confocal scanning laser microscopy showed that AP-endonuclease was primarily localized in the nucleus but also in mitochondria. Our data are the first to demonstrate the inducibility of AP-endonuclease by a human class I carcinogen associated with oxidant stress in normal cells of the lung.

CT abnormalities in schizophrenia. A preliminary study of their correlations with P300/P200 electrophysiological features and positive/negative symptoms.

Computed tomographic scans were scored blindly for the size of cerebrospinal fluid spaces in a group of nine medicated schizophrenics and a group of nine age-matched normal volunteers without psychiatric or medical problems. Overall, ten of the 18 computed tomography (CT) features measured were significantly enlarged in the schizophrenic group. These abnormal CT features were then correlated with electrophysiological and clinical measurements performed on the schizophrenic patients. Left sylvian fissure enlargement, thought to reflect temporal lobe tissue loss, was highly correlated with a left temporal scalp region feature of the auditory P300 measure (T3 electrode) that differentiated schizophrenics and normals, and both the left sylvian fissure enlargement and the P300 measure were highly correlated with positive symptoms (total score on the Scale for the Assessment of Positive Symptoms). Frontal superficial (cortical) sulcal enlargement was prominent in the schizophrenic group and was highly correlated with another electrophysiological measure, auditory P200, at left central scalp locations. There was no significant correlation between left sylvian fissure and frontal sulcal enlargement within the schizophrenic group, and intercorrelations between CT variables in the schizophrenic group were, in general, less significant than in the control group. Although we should be cautious about generalizability because of the small number of patients, these data are compatible with the hypothesis that different subgroups of schizophrenic pathological features are characterized by different CT, electrophysiological, and clinical presentations.

Auditory P300 abnormalities and left posterior superior temporal gyrus volume reduction in schizophrenia.

Abnormalities in the auditory P300 event-related potential are one of the most robust findings in schizophrenia. To investigate the brain source(s) of this major functional abnormality, we combined P300 recordings with the use of a new generation of magnetic resonance imaging (MRI) technology to examine specific temporal lobe gray matter regions of interest in schizophrenics and normal controls. In schizophrenics, gray matter volume reductions in the left posterior superior temporal gyrus (STG), which includes Heschl's gyrus and the planum temporale, were highly and specifically associated with both P300 amplitude reduction and left < right topographic asymmetry. In contrast, left hippocampus and parahippocampal gyrus gray matter volume reductions, although present in schizophrenics, were not associated with any P300 abnormalities. There were also no statistically significant correlations between P300 amplitude at any of the central or left-sided electrode sites or any of the MRI-defined volumes of gray matter regions of interest in the right temporal lobe, superior frontal gyrus, or cingulate gyrus; additional work will thus be required to determine the role of these regions, if any, in P300 generation, along with the role of other brain areas not examined in the present study. These initial data appear most compatible with a model that postulates a major role for bilateral STG sources in P300 generation: The strongly asymmetric STG volume reduction (left < < right STG volume) found in many schizophrenic subjects produces asymmetric P300 amplitudes (left < < right) at lateral electrode sites, where the influence of the abnormal region is most easily detected.

Increased rate of P300 latency prolongation with age in schizophrenia. Electrophysiological evidence for a neurodegenerative process.

BACKGROUND: The latency of the P300 event-related potential is prolonged in disorders associated with neural damage and degeneration and also becomes prolonged in the course of neural changes that accompany aging. We tested whether the rate of P300 latency increase with age was greater in male schizophrenic patients than in normal subjects because a steeper slope in schizophrenia would suggest a progressive neurodegenerative process. We also evaluated a subset of these subjects for changes in brain volumes as determined by magnetic resonance imaging. METHOD: The P300 component was elicited during an auditory "oddball" paradigm and was recorded from 47 male patients with chronic schizophrenia whose mean age at onset was 22.4 years and from 47 age-, handedness-, and gender-matched control subjects. The relation of P300 latency and amplitude to age within each group was evaluated using correlation and regression analyses. Brain volumes determined via magnetic resonance imaging were evaluated by quantitative volumetric analyses of images acquired with three-dimensional Fourier transform and double echo-spin echo-pulse sequences. RESULTS: The slope of P300 latency on age was steeper for schizophrenic patients than for normal control subjects at midline frontal and central electrode sites. The slope of N100 latency did not differ, implying that the P300 differences were not likely to be due to peripheral hearing loss or damage affecting the initial stages of neural processing. Posterior superior temporal gyrus gray matter volume determined via magnetic resonance imaging significantly diminished with age on the left side in patients with schizophrenia but not on the right side or in controls; these slopes were not, however, statistically significantly different from each other. CONCLUSIONS: These findings provide preliminary evidence that male patients with chronic schizophrenia experience a neurodegenerative process that becomes evident in adulthood and is reflected by the rate of change of P300 latency with age. Whether this process is due to the primary effects of schizophrenia or is secondary to factors associated with schizophrenia's chronic course and treatment remains a question for future investigation.

P300 in schizophrenia: confirmation and statistical validation of temporal region deficit in P300 topography.

Comparison of normal and medicated schizophrenic groups on the auditory P300 component of the event-related potential confirmed our earlier finding of a left temporal deficit in P300 amplitude in schizophrenia. A difference in P300 topography between groups was evident in both color mapping and in grand-averaged waveforms, which was statistically validated by the presence of a group-by-scalp region interaction (p less than 0.05). The left temporal area in schizophrenics was denoted as the region of greatest deficit and of maximal statistical separation (p less than 0.05) relative to normals by t statistic mapping (SPM), Hotelling's T-squared "protected" contrasts of individual scalp regions, and the relative ratio of left scalp amplitudes to right scalp amplitudes. The left temporal scalp region yielding maximal group separation in the previous study also statistically separated the schizophrenic group from the normal group. This feature correctly differentiated 9 of 11 schizophrenics and 7 of 9 controls. These findings are compatible with other histological, metabolic, and electrophysiological studies suggesting temporal lobe abnormality in schizophrenia.

Correlations between abnormal auditory P300 topography and positive symptoms in schizophrenia: a preliminary report.

P300 component amplitude in the left temporal scalp region, shown in three previous studies to differentiate normals from schizophrenics, was found to be significantly correlated with the Thought Disorder Index (TDI) and the Scale for the Assessment of Positive Symptoms (SAPS). These correlations occurred primarily in the P300 waveform derived from the Goodin paradigm. These findings suggest a brain processing disturbance in positive symptom schizophrenia that may be reflected by electrophysiological abnormalities detectable in the temporal scalp region.

The auditory N2 component in schizophrenia: relationship to MRI temporal lobe gray matter and to other ERP abnormalities.

The N2 component of the auditory event-related potential (ERP) indexes cognitive processes involved in the categorization of deviant stimuli. Although N2 amplitude and latency abnormalities have been reported in schizophrenia, their relationship to MRI structural changes, clinical status, and P3 abnormalities has not been defined. We therefore studied the auditory N2 and P3 components elicited by an oddball paradigm in 15 right-handed male subjects with schizophrenia and 14 control subjects who had quantitative MRI measures of temporal lobe gray-matter structures. To provide a methodological comparison, we measured the auditory N2 from both the target ERP (N2t) and the target-minus-frequent ERP difference (N2d) waveforms. Both N2t and N2d amplitude were bilaterally reduced in schizophrenics, with N2d showing a more pronounced reduction. Within the schizophrenic group, N2 amplitude reduction was associated with reduction in gray-matter volume of the left superior temporal gyrus (STG) and of medial temporal lobe structures bilaterally, and clinically, with greater chronicity. P3 amplitude, in contrast, correlated only with left posterior STG volume, and was more prominently associated with delusions and thought disorder. These findings suggest that the N2 and P3 components, though occurring sequentially in the ERP, tap separable anatomic and behavioral abnormalities in schizophrenia.

Long-latency event-related potentials in the evaluation of cognitive function in children.

The endogenous auditory P300 event-related potential (P3) has been used to differentiate functional and organic cognitive disorders in adults. We found that children with organic cognitive impairments (as determined by the Halstead-Reitan [HR] test) had greater P3 latencies than children with normal HR evaluations. The P3 and HR showed 85% agreement in independent assessments of functional or organically based cognitive impairment in children. Mini-Mental-State, IQ, EEG evaluations, and clinical suspicions of "organicity" with respect to cognitive function were similarly associated with P3 latency.

Neuroleptics improve sustained attention in schizophrenia. A study using signal detection theory.

To test the hypothesis that antipsychotic drugs improve attentional processes in schizophrenia, we used a computer-controlled, perceptually degraded continuous performance test (CPT), based on signal detection theory. CPT stimuli were degraded (blurred) to reduce discriminability so that signal detection analysis could be used to distinguish specific attentional processes, as measured by A', from nonspecific factors, as measured by B". Thirteen medicated and 12 neuroleptic-withdrawn schizophrenics visually monitored digits to detect a target under perceptually undegraded and degraded conditions. The principal result was that the neuroleptic-withdrawn patients showed a significant decline in the attention-specific measure of A' over time on task only for the degraded targets, independent of changes in the nonspecific index of B". These results demonstrate that neuroleptic withdrawal may compromise specific attentional processes, namely the ability to sustain attention, as measured by a precise performance task which controlled for nonspecific factors.

Bleomycin-induced unscheduled DNA synthesis in non-permeabilized human and rat hepatocytes is not paralleled by 8-oxo-7,8-dihydrodeoxyguanosine formation.

The genetic toxicity of the antitumour antibiotic bleomycin (BLM) is thought to involve the formation of a reactive oxygen intermediate. 8-Oxo-7,8-dihydrodeoxyguanosine (oxo8dG), an oxidation product of deoxyguanosine, is one of the major products formed when isolated DNA is exposed to oxygen radical generating systems. Gamma-irradiation (10-500 Gy 60Co; 10 Gy/min) or BLM and Fe2+ (37.5-150 U/L and 0.5 mM, respectively) treatment of isolated DNA (0.25 mg/mL) increased oxo8dG above background. In the latter case, the effect was greater than that with Fe2+ (0.5 mM) alone and was dependent on the dose of BLM. When DNA was irradiated with 500 Gy60Co, deoxyguanosine oxidation was inhibited by antioxidants (ethanol: 37.5 and 98% inhibition at 2 and 20 mM, respectively; mannitol: 20.5, 60 and 92% inhibition at 0.1, 1.0 and 10 mM, respectively). Similarly the BLM-induced production of oxo8dG was inhibited (64%) by mannitol (10 mM). BLM also caused production of base propenals on interaction with isolated DNA. In contrast, oxo8dG was not induced above background concentration (27 mol oxo8dG/10(6) mol dG) in permeabilized (37 degrees) and non-permeabilized (4 degrees and 37 degrees) rat hepatocytes treated with BLM (260 U/L). Despite this, there was extensive BLM-induced unscheduled DNA synthesis (10 and 100 U/L) in non-permeabilized rat and human hepatocytes in the absence of hydroxyurea. These findings, in accord with other observations, draw into question the role of .OH in BLM-induced DNA damage and the mimicry of ionizing radiation in cellular systems.

Possible role of lipid peroxidation in the induction of NF-kappa B and AP-1 in RFL-6 cells by crocidolite asbestos: evidence following protection by vitamin E.

Asbestos fibers cause persistent induction of the oxidative stress sensitive transcription factors nuclear factor kappa-B (NF-kappa B) and activator protein-1 (AP-1) in mammalian cells. These transcription factors play an important role in the regulation of cellular activity. Lipid peroxidation, mediated by reactive oxygen species, is thought to be a possible mechanism in the pathogenicity of asbestos fibers. These studies were designed to determine if crocidolite asbestos-induced lipid peroxidation plays a role in the mechanism of formation of NF-kappa B and AP-1. Treatment of a rat lung fibroblast cell line (RFL-6) with crocidolite asbestos in the presence and absence of the membrane antioxidant vitamin E decreased the levels of crocidolite-induced AP-1 and NF-kappa B to background levels. Preincubation of RFL-6 cells with 5,8,11,14-eicosatetraynoic acid, an inhibitor of arachidonic acid metabolism, prior to exposure to crocidolite, abrogated crocidolite-induced NF-kappa B DNA-binding activity to background levels. Coincubation with indomethacin, a cyclooxygenase inhibitor, had no effect on NF-kappa B DNA-binding activity induced by crocidolite. However, nordihydroguaiaretic acid, a lipoxygenase inhibitor, decreased levels of NF-kappa B to background levels. This would suggest that lipoxygenase metabolites of arachidonic acid, produced following lipid peroxidation, are involved in the cellular signalling events to NF-kappa B transcription factor induction by asbestos.

Cell signaling pathways elicited by asbestos.

In recent years, it has become apparent that minerals can trigger alterations in gene expression by initiating signaling events upstream of gene transactivation. These cascades may be initiated at the cell surface after interaction of minerals with the plasma membrane either through receptorlike mechanisms or integrins. Alternatively, signaling pathways may be stimulated by active oxygen species generated both during phagocytosis of minerals and by redox reactions on the mineral surface. At least two signaling cascades linked to activation of transcription factors, i.e., DNA-binding proteins involved in modulating gene expression and DNA replication, are stimulated after exposure of lung cells to asbestos fibers in vitro. These include nuclear factor kappa B (NF kappa B) and the mitogen-activated protein kinase (MAPK) cascade important in regulation of the transcription factor, activator protein-1 (AP-1). Both NF kappa B and AP-1 bind to specific DNA sequences within the regulatory or promoter regions of genes that are critical to cell proliferation and inflammation. Unraveling the cell signaling cascades initiated by mineral dusts and pharmacologic inhibition of these events may be important for the control and treatment of mineral-associated occupational diseases.

Event-related potentials in schizophrenia: their biological and clinical correlates and a new model of schizophrenic pathophysiology.

Evidence is growing that schizophrenic patients show significant structural damage in the temporal lobe limbic system. We review event-related potentials abnormalities (ERPs) in schizophrenia that may be related to dysfunction in this brain region or its inputs; ERPs discussed include the N100/P200, P300 and N400 components. Additional CT and clinical data have led our laboratory to a unifying working hypothesis of the presence of temporal lobe damage in schizophrenics that is evinced electrophysiologically as ERP alterations, structurally as tissue loss/derangement, and clinically as positive symptoms. The final section of this paper presents a new model of at least one form of schizophrenic pathology that, while speculative, incorporates experimentally based data from both our ERP work and from basic cellular physiology and pharmacology. The model proposes that positive symptoms of schizophrenia are related to limbic system pathology and in particular to a dysregulation of the NMDA form of excitatory amino acid transmission, potentiated by stress, and leading to cell damage and death due to 'excitotoxicity'.

Premorbid adjustment in schizophrenia: implications for psychosocial and ventricular pathology.

Premorbid adjustment in schizophrenia is thought important (1) as a predictor of current pathology and course, and (2) as a psychosocial expression of brain pathology preceding psychosis. Its valid and reliable measurement, however, pose a major challenge. To address this issue we interviewed 12 chronic male schizophrenic veterans and their first degree relatives, plus 12 age and social class of origin matched normal controls and their relatives, using the Cannon-Spoor et al. Premorbid Adjustment Scale (PAS), for which we developed our own semi-structured interview. Objective data from school records were also obtained. Schizophrenic's PAS scores were significantly poorer, irrespective of whether PAS scores were based on information from subjects, first degree relatives or from 'combined sources'. PAS scores were worse at all developmental epochs, with a marked divergence beginning in late adolescence. Worse premorbid adjustment in schizophrenia was also highly correlated with current clinical state, more current negative symptoms, less independent living and longer duration of hospitalization. Additionally, worse premorbid adjustment in schizophrenia was associated with larger Magnetic Resonance (MR) Ventricular Brain Ratio (VBR) in an exploratory analysis using a subset of these patients. Premorbid adjustment, rigorously measured, is poorer in schizophrenics than in normal controls and correlates with psychosocial and ventricular pathology in schizophrenia.

Measurement of visual sustained attention in schizophrenia using signal detection analysis and a newly developed computerized CPT task.

Sustained attention in schizophrenia was assessed with a newly developed, computer-controlled, modified version of the continuous performance test in which specific attentional effects can be empirically distinguished from nonspecific factors by signal detection theory (SDT). Results indicated that patients showed a more rapid decline in specific attentional, but not nonspecific processes, as measured by SDT parameters of A' and B", respectively.