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.

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.

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.

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.

Inter-observer reliability of clinical outcome measures in a lower limb amputee population.

PURPOSE: In an attempt to find a more clinically useful functional outcome measure specifically tailored for lower limb amputees undergoing inpatient prosthetic rehabilitation, a 6-month prospective assessment of inter-rater reliability for Harold Wood-Stanmore Mobility Scale Data, including two handicap scales, was undertaken. An analysis of the data is presented in this paper. METHODS: An inter-rater reliability study was undertaken using four observers to complete admission and discharge scores for the three disability/handicap scales on 14 consecutive patients over 6 months. RESULTS: The disability mobility scale demonstrated perfect observer agreement on admission and at discharge the inter-rater reliability for this measure was high (0.83). By contrast, reliability between observers for admission scores on the handicap mobility scale was poor at 0.49 but reasonably high on discharge (0.83). On admission, inter-rater reliability for handicap physical independence was very low (0.15). At discharge, reliability improved to 0.69 being more consistent with results achieved for the other axes. CONCLUSIONS: This study confirms the good inter-rater reliability demonstrated previously in the literature but reveals poor inter-rater reliability for the two handicap scales. The latter will require modification before they can be used with confidence in conjunction with the disability scale.

Lipid and DNA oxidative damage in experimentally induced hepatic porphyria in C57BL/10ScSn mice.

Patients with porphyria cutanea tarda (PCT) develop hepatocellular carcinoma as a late consequence. Pre-loading of C57BL/10ScSn mice with iron greatly sensitizes them to the induction of hepatic porphyria caused by hexachlorobenzene (HCB). HCB will also cause liver tumors in experimental animals. Elevated liver iron stores are implicated in the development of some human liver cancers in connection with its known catalytic role in generation of highly reactive activated oxygen species. The aim of this study was to determine the lipid and DNA oxidative damage in iron and HCB-induced porphyric mice. C57BL/10ScSn mice received i.p. injections of dextran sulfate (control), iron (Imferon) or combined iron and HCB. 6 weeks after treatment plasma ALT levels and hepatic free iron, porphyrin, lipid peroxides and 8-hydroxyguanosine (8-OHdG) levels were analyzed. Hepatic porphyrin level was significantly (p < 0.001) increased following combined iron/HCB treatment as compared to control mice. The level of lipid peroxides increased 9-fold (p = 0.001) and 35-fold (p < 0.001) after iron and iron/HCB treatment respectively, whereas the level of 8-OHdG was increased 2.5-fold (p = 0.002) and 7.5-fold (p < 0.001) after iron and iron/HCB treatment respectively as compared to control mice. The authors conclude that iron overload in conjugation with HCB induce lipid and DNA oxidative damage in C57BL/10ScSn mice. DNA oxidative damage may be important in the early events of hepatic carcinogenesis in experimental porphyria.

Vitamin E protects against iron-hexachlorobenzene induced porphyria and formation of 8-hydroxydeoxyguanosine in the liver of C57BL/10ScSn mice.

The effect of vitamin E treatment on total porphyrin content, lipid peroxidation (LOOH) and 8-hydroxydeoxyguanosine (8-OHdG) was studied in the livers of C57BL/10ScSn mice following hexachlorobenzene (HCB) and iron treatment. HCB was administered i.p. (totalling 300 mg/kg) twice, with 1 week interval. Three days after the first HCB injection iron-dextran was given i.p. (500 mg Fe per kg). Vitamin E was administered weekly (20 mg/kg) by s.c. injection. Both total hepatic porphyrin and LOOH levels were significantly (P<0.001) increased in the HCB-iron treated group as compared with the control group. Mice treated additionally with vitamin E had significant (P<0.001) lower levels as compared with the HCB-iron group. Similarly, the levels of 8-OHdG were significantly (P<0.001) increased above controls after HCB-iron treatment and this increase was reduced after co-treatment with vitamin E (P<0.02). The data support the hypothesis that the mechanism of hepatic porphyrinogenicity of HCB with iron overload is an oxidative free radical process.

Reappraisal of filter effects on P300 voltage and latency.

The selection of which high-pass filter cutoff to use in P300 studies continues to be a serious methodological consideration. To determine whether there was an optimal range of bandpass widths-a range in which P300 voltage and latency would not show statistically significant differences-the authors recorded P300 responses to the auditory "oddball" paradigm from Cz and Pz electrodes in a group of eight healthy males. The authors used high-pass filter cutoffs of 0.01, 0.1, 0.3, and 1.0 Hz with low-pass filter cutoffs of 30 and 100 Hz and measured both P300 peak voltages and P300 integrated mean voltages at 12 bandpass settings. There were statistically significant differences in 7 out of 12 bandpass comparisons for P300 peak voltages and in 7 out of 12 bandwidth comparisons for P300 integrated mean voltages. For P300 latencies, there were statistically significant differences in 9 out of 12 bandwidth comparisons. Based on these results, the best recommendation, therefore, is that the high-pass filter be set no higher than 0.3 Hz.

Persistent depletion of I kappa B alpha and interleukin-8 expression in human pulmonary epithelial cells exposed to quartz particles.

Chronic inflammation and fibrosis following quartz inhalation has been associated with persistent up-regulation of several "pro-inflammatory" genes, which are commonly regulated by nuclear factor kappa-B (NF-kappaB). Transcription of the NF-kappaB-inhibitor IkappaBalpha is also under NF-kappaB control, and its de novo synthesis is considered to comprise a negative feedback loop in transient inflammation. To investigate this mechanism in particle inflammation, we have studied IkappaBalpha degradation in A549 cells exposed to DQ12-quartz or TiO(2), in relation to the expression of IL-8. Although both quartz and TiO(2) were found to cause IkappaBalpha degradation, only quartz elicited a mild IkappaBalpha depletion, first appearing at 4 h. TiO(2) was found to cause a higher short-term increase in IkappaBalpha mRNA-expression compared to quartz, whereas the early enhancement of IL-8 expression and release was similar for both particles. Up-regulation of IL-8 expression was found to persist with quartz only. Cotreatment with PDTC and curcumin reduced particle-elicited IL-8 response, whereas cycloheximide caused enhancement of IL-8 mRNA expression in both the quartz- and TiO(2)-treated cells. Our results demonstrate that mineral dusts cause IkappaBalpha degradation, a transient increase in de novo synthesis of IkappaBalpha, and enhanced IL-8 expression in human pulmonary epithelial cells. While IkappaBalpha degradation and early IL-8 expression seem to be general particle phenomena, particle-specific characteristics impact on activation of IkappaBalpha gene transcription, apparently accounting for the different proinflammatory IL-8 responses seen with quartz and TiO(2) in the longer term. These observations may provide an explanation for the transient versus the persistent pulmonary inflammatory status and subsequent differences in pathogenic potency of TiO(2) and quartz.

Increased calcium influx in a monocytic cell line on exposure to ultrafine carbon black.

Ultrafine particles have been shown to induce pro-inflammatory effects both in vivo and in vitro. Increased expression of pro-inflammatory genes probably requires the activation of specific transcription factors such as nuclear factor kappa B (NF-kappaB) via a number of possible pathways including Ca2+ and reactive oxygen species. The fluorescent dye fura 2, was used to measure cytosolic Ca2+ in the human monocytic cell line, Monomac 6 on exposure to 66 microg x mL(-1) of either ultrafine carbon black (ufCB; diameter 14 nm), carbon black (CB; diameter 260 nm), quartz (diameter 1.45 microm), or medium alone. UfCB but not fine CB induced a 1.6-fold increase (p<0.01) in the resting cytosolic Ca2+ concentration of Monomac 6 cells. In addition ufCB induced a 2.6-fold increase (p<0.001) in the response to the endoplasmic reticulum Ca2+- adenosine triphosphatase (ATPase) inhibitor, thapsigargin, suggesting the Ca2+ release-activated Ca2+ current across the plasma membrane was enhanced. This response was inhibited by the removal of extracellular Ca2+ and by the Ca2+ channel blocker, verapamil. In addition, ufCB stimulated the entry of extracellular Mn2+. Finally, the antioxidants mannitol and nacystelin both inhibited the effects of ufCB on the response to thapsigargin. These data suggest that ultrafine carbon black particles stimulated an increase in cytosolic Ca2+, possibly through the entry of extracellular Ca2+ via Ca2+ channels in the plasma membrane. The particles may in part activate the opening of Ca2+ channels via a mechanism involving reactive oxygen species.

Cell Signaling in Mesothelial Cells by Asbestos: Evidence for the Involvement of Oxidative Stress in the Regulation of the Epidermal Growth Factor Receptor.

Asbestos has been shown to stimulate the mitogen-activated protein kinase signaling cascade after autophosphoryiation of the epidermal growth factor recptor (EGF-R), an event important in regulating the response of cells to extracellular signals. In studies reported here, we have examined whether mineral fibers with known carcinogenicity can be discriminated from nonpathogenic fibers by their ability to upregulate expression of EGF-R protein in mesothelial cells. Crocidolite and erionite, two fibrous preparations known to induce mesothelioma, increased expression of EGF-R protein in a time- and dose-dependent manner, whereas milled (nonfibrous) crocidolite and chrysotile asbestos, two preparations with much less or no ability to induce mesothelioma, did not. Intense patterns of EGF-R protein expression were linked to mesothelial cells phagocytosing long fibers as observed by phase-contrast microscopy. To determine the importance of EGF-R expression in these cells, we assessed downstream signaling events in rat pleural mesothelial (RPM) cells by looking at the induction of activator protein-1 (AP-I), a transcription factor that controls the transition to S phase in the cell cycle, leading to cell proliferation. Crocidolite induced AP-I in RPM cells in a dose-dependent manner, and this induction of AP-I in RPM cells was inhibited by coincubation with tyrphostin AG 1478, a potent inhibitor of the EGF-R. To examine the mechanism of induction of EGF-R in RPM cells by asbestos, RPM cells were treated with crocidolite in the presence and absence of the antioxidant N-acetylcysteine (NAC). Reduced glutathione (GSH) was examined as a marker of oxidative stress and the expression of EGF-R protein was measured. Crocidolite asbestos caused a dose-dependent depletion of GSH in RPM cells, and the presence of NAC ameliorated the expression of EGF-R protein by crocidolite. Our data suggest that carcinogenic fibers induce EGF-R via a mechanism involving oxidative stress initiating cell signaling cascades in mesothelial cells leading to cell proliferation and carcinogenesis.

Increased expression of epidermal growth factor receptor in rat pleural mesothelial cells correlates with carcinogenicity of mineral fibres.

Asbestos fibres have been shown to stimulate the mitogen-activated protein kinase signalling cascade in rat pleural mesothelial (RPM) cells after autophosphorylation of the epidermal growth factor receptor (EGFR). We examined if mineral fibres with known carcinogenicity can be discriminated from materials with less or no carcinogenicity by their ability to up-regulate expression of EGFR protein in RPM cells in vitro. Crocidolite and erionite, two fibrous preparations with marked potential to induce mesothelioma, were associated with increases in EGFR protein expression over sham controls, whereas chrysotile asbestos and milled (non-fibrous) crocidolite did not. Intense patterns of EGFR protein expression were linked to RPM cells phagocytosing long fibres. To determine the role of EGFR expression in these cells, we assessed cell proliferation using an antibody against proliferating cell nuclear antigen (PCNA) in combination with an antibody against EGFR. In these co-localization studies, cells showed intense staining for EGFR protein 24 h before being PCNA positive at 48 h. These results suggest that carcinogenic fibres induce EGFR and initiate cell signalling cascades in mesothelial cells, leading to cell proliferation and carcinogenesis.

Development and psychometric testing of the Breastfeeding Self-Efficacy Scale.

Many new mothers discontinue breastfeeding prematurely. Researchers have shown that maternal confidence is an important factor in the continuation of breastfeeding. The purpose of this methodological study was to develop and conduct preliminary psychometric assessment of an instrument to measure confidence in new breastfeeding mothers. Using self-efficacy theory as a conceptual framework, the Breastfeeding Self-Efficacy Scale (BSES) was developed and content validity was judged by a panel of experts and through interviews with experienced breastfeeding mothers. Following a pilot test, the revised BSES was assessed with 130 in-hospital breastfeeding mothers for reliability and validity, including internal consistency, principal components factor analysis, comparison of contrasted groups, and correlations with measures of similar constructs. Support for predictive validity was demonstrated with positive correlations between BSES scores and infant feeding patterns at 6 weeks postpartum. Following further testing, this instrument may be used to identify new mothers with low breastfeeding confidence who are at high risk to prematurely discontinue breastfeeding.

Clinical genetics: an overview.

It is imperative that clinicians understand basic human genetic concepts. In this article, the patterns of inheritance for single gene disorders are described and include the traditional Mendelian, nontraditional, and multifactorial patterns. Next, chromosomal and structural abnormalities are described, followed by a description of the current measures by which genes are detected, including gene mapping and polymorphisms, and concluding with cytogenetic, molecular, and biochemical testing.

Implications of genetic testing of children and adolescents.

Advances in genetic technology increase the ability to test children and adolescents for late-onset conditions, disease susceptibilities, and carrier status. Genetic tests may offer medical or psychologic benefits but may also create harm; alteration of the child's self-concept or parent-child bonds and risk of stigmatization are examples of the latter. The article examines developmental theories concerning children's ability to make choices as well as informed consent and ethical considerations in genetic testing. Because optimal care requires awareness of the complex psychosocial and ethical issues involved in childhood genetic testing, nurses must be prepared to acknowledge and discuss such issues with families.

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.

The role of oxidative stress in the prolonged inhibitory effect of ultrafine carbon black on epithelial cell function.

Respired ultrafine particles induce a greater inflammation in rat lungs than fine particles; we have hypothesized that this is due to their comparatively huge number and surface area for the production of free radicals. We tested this hypothesis by studying the effects of fine and ultrafine (uf) carbon black (CB) particles in comparison with quartz on A549 human type II alveolar epithelial cells, particularly with respect to the oxidative properties of these particles. Treatment with fine CB (diameter 260nm), and quartz (up to 0.78mug/mm(2)) for 24 hours significantly (P<0.05) decreased the A549 cells metabolic competence, as measured by the ability to reduce MTT to a formazan product. The inhibitory effects of uf CB only became significantly different (P<0.05) relative to the control at 48 hours, by which time the effects of fine CB and quartz were no longer significant. The inhibition of MTT reduction by uf CB was prevented by the hydroxyl radical scavenger mannitol (2mm). In addition, measurement of reactive oxygen species production using supercoiled plasmid DNA showed that uf CB exhibited significantly more free radical activity than fine CB (P<0.05). In the absence of serum, uf CB depleted reduced glutathione at 6 hours (P<0.008). In contrast, CB did not significantly alter reduced or oxidized glutathione. Hence, compared with fine CB, uf CB exhibited greater free radical activity, greater inhibition of the reduction of MTT at 48 hours (prevented by mannitol) and a depletion of reduced glutathione. These results suggest that uf CB induces a greater oxidative stress than fine CB, and that this may play a role in the toxicological effects of this ultrafine particle.

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.