Is fascia iliaca compartment block or intravenous opioid analgesia better when positioning patients with fractured neck of femur for spinal anaesthesia?

Patients with a fractured neck of femur require effective analgesia to improve positioning before the administration of spinal anaesthetic. This article discusses the evidence to show whether fascia iliaca compartment block or intravenous opioid analgesia is preferable in this situation.

Self-reported Dysphagia and Pharyngeal Volume Following Whiplash Injury.

Difficulty swallowing has been reported following whiplash injury; however, the reasons remain poorly understood. A possible factor may be the observed changes in pharyngeal volume. The current exploratory study was designed to examine the prevalence of self-reported dysphagia after whiplash and the relationship with recovery status and change in pharyngeal volume. Data were available from a longitudinal study of adults with whiplash. Data included magnetic resonance imaging (MRI) of the cervical spine, the Dysphagia Handicap Index (DHI), and Neck Disability Index (NDI) collected over four timepoints (< 1 week, 2 weeks, 3 months, and 12 months post-injury). Initial cross-sectional analysis examined 60 patients with DHI data from at least one timepoint. A second, longitudinal analysis was conducted on 31 participants with MRI, NDI, and DHI data at both early (< 1-2 weeks) and late (3-12 months) timepoints. The pharynx was contoured on axial T2-weighted MRI slices using OsiriX image processing software and pharyngeal volume (mm3) was quantified. In the 60-patient cohort, prevalence of self-reported dysphagia (DHI ≥ 3) was observed in 50% of participants at least once in 12 months (M = 4.9, SD 8.16, range 0-40). In the longitudinal cohort (n = 31), mean total DHI significantly (p = 0.006) increased between early and late stages. There was no relationship (p = 1.0) between dysphagia and recovery status, per the NDI% score. Pharyngeal volume remained stable and there was no relationship between dysphagia and pharyngeal volume change (p = 1.0). This exploratory study supports the need for further work to understand the nature of dysphagia, extent of functional compromise, and the underlying pathophysiology post-whiplash.

Impact of time of day on radiology image interpretations.

AIM: To examine the impact of the time of day on radiologists' mammography reading performance. MATERIALS AND METHODS: Retrospective mammographic reading assessment data were collected from the BreastScreen Reader Assessment Strategy database and included timestamps of the readings and reader-specific demographic data of 197 radiologists. The radiologists performed the readings in a workshop setting with test case sets enriched with malignancies (one-third of cases were malignant). The collected data were evaluated with an analysis of covariance to determine whether time of day influenced radiologists' specificity, lesion sensitivity or the jackknife alternative free-response receiver operating characteristic (JAFROC). RESULTS: After adjusting for radiologist experience and fellowship, specificity varied significantly by time of day (p=0.027), but there was no evidence of any significant impact on lesion sensitivity (p=0.441) or JAFROC (p=0.120). The collected data demonstrated that specificity during the late morning (10.00-12.00) was 71.7%; this was significantly lower than in the early morning (08.00-10.00) and mid-afternoon (14.00-16.00), which were 82.74% (p=0.003) and 81.39% (p=0.031), respectively. Specificity during the late afternoon (16.00-18.00) was 73.95%; this was significantly lower than in the early morning (08.00-10.00) and mid-afternoon (14.00-16.00), which were 82.74% (p=0.003) and 81.39% (p=0.031), respectively. CONCLUSION: The results indicated that the time of day may influence radiologists' performance, specifically their ability to identify normal images correctly.

In-situ SEM observation of grain growth in the austenitic region of carbon steel using thermal etching.

A novel heat stage, recently developed for use within the Scanning Electron Microscope, has facilitated Secondary Electron imaging at temperatures up to 850°C. This paper demonstrates one of the applications of in-situ elevated temperature Scanning Electron Microscope imaging: observation and quantification of grain growth within the austenitic region of carbon steels. The resulting Secondary Electron data have used the technique of thermal etching to capture possible 'abnormal grain growth' in the austenitic region. Previous ex-situ and post-heating results from carbon steels indicate normal, non-linear grain growth. Therefore, this new dataset provides greater insight into the heat treatment of steels. From comparison of the in-situ data with the overall grain growth, measured ex-situ, it is further concluded that abnormal grain growth is representative of the growth at temperature. Thus, the heating and cooling parts of the heat treatment are likely to account for the non-linearity previously documented in ex-situ results and, hence, the range of powers recorded when fitting power law models for steel grain growth. The ability of data derived from in-situ thermal etching to represent the microstructure of the entire surface and the bulk material is also considered. LAY DESCRIPTION: A novel heating stage has recently been developed for use within the Scanning Electron Microscope (SEM); an instrument that uses electrons to image specimen surfaces at very high magnifications. The development of the heating stage has facilitated imaging at temperatures up to 850°C of the structure and topographic features of metals using two different detectors. This study focusses on observation and quantification of grain growth in steels at temperatures of 800  C. In Materials Science, grains refer to crystals of varying, randomly distributed, small sizes that together make up a solid metal. The temperature of 800  C is used as it is the desired temperature to heat treat steels in order to produce more favourable physical properties. It is also the temperature above which the material undergoes a phase change; phase change is a transition where the atoms rearrange from one order within a grain to another. In the case of steel, at room temperature atoms will be in what is called a ferrite phase (one order) but at 800  C, they will be in a different order within the grains, known as the austenite phase. Hence, the uniqueness of this dataset as the grain growth captured is in the high temperature steel phase of austenite. The steel samples used are made up of 0.4% Carbon, 99% iron and some manganese and other trace elements. The resulting data have, for the first time, shown so called 'abnormal grain growth' which is represented by a linear relationship between grain size and time. Abnormal grain growth is also observed in the images where it can be seen how larger grains grow at a high rate at the expense of smaller ones. Previous data taken after cooling of steels indicate normal non-linear grain growth. Therefore, it is reasonable to suggest, this new dataset provides greater insight into the heat treatment processing of steels, demonstrating that they are potentially more complex than previously thought.

In the digital era, architectural distortion remains a challenging radiological task.

AIM: To compare readers' performance in detecting architectural distortion (AD) compared with other breast cancer types using digital mammography. MATERIALS AND METHODS: Forty-one experienced breast screen readers (20 US and 21 Australian) were asked to read a single test set of 30 digitally acquired mammographic cases. Twenty cases had abnormal findings (10 with AD, 10 non-AD) and 10 cases were normal. Each reader was asked to locate and rate any abnormalities. Lesion and case-based performance was assessed. For each collection of readers (US; Australian; combined), jackknife free-response receiver operating characteristic (JAFROC), figure of merit (FOM), and inferred receiver operating characteristic (ROC), area under curve (Az) were calculated using JAFROC v.4.1 software. Readers' sensitivity, location sensitivity, JAFROC, FOM, ROC, Az scores were compared between cases groups using Wilcoxon's signed ranked test statistics. RESULTS: For lesion-based analysis, significantly lower location sensitivity (p=0.001) was shown on AD cases compared with non-AD cases for all reader collections. The case-based analysis demonstrated significantly lower ROC Az values (p=0.02) for the first collection of readers, and lower sensitivity for the second collection of readers (p=0.04) and all-readers collection (p=0.008), for AD compared with non-AD cases. CONCLUSIONS: The current work demonstrates that AD remains a challenging task for readers, even in the digital era.

Cardiorespiratory responses during functional electrical stimulation cycling and electrical stimulation isometric exercise.

STUDY DESIGN: Prospective experimental. OBJECTIVES: To compare the cardiorespiratory responses with electrical stimulation (ES) producing either dynamic leg cycling or intermittent isometric leg contractions using the same ES protocol. SETTING: Sydney, Australia. METHODS: Eight paraplegics (T4-T11) performed ES exercise sessions on two separate days. On day 1, cardiorespiratory responses were measured during 5 min of rest followed by 35 min of cycling, and finally 15 min of intermittent isometric exercise using the same ES parameters. On the second day, after 5 min of rest, 35 min of isometric exercise was performed followed by 15 min of cycling. RESULTS: There were no significant differences during the first 35 min of exercise on each day comparing the two modes of exercise for average rate of oxygen consumption (cycling, 534±128 ml min(-1); isometric 558±146 ml min(-1); P=0.451), the average heart rate (cycling, 93±15 b.p.m.; isometric 95±17 b.p.m.; P=0.264) or minute ventilation (cycling, 23.0±6.5 l min(-1); isometric 23.8±6.7 l min(-1); P=0.655). In addition, there were no significant differences between exercise modes for any peak cardiorespiratory values recorded during the initial 35 min of exercise or the following 15 min crossover exercise phase. CONCLUSION: The current data found that intermittent ES leg isometric exercise elicited a similar cardiorespiratory response compared with functional ES leg cycling, suggesting it should be investigated as a viable alternative intervention for increasing whole body metabolic rate during sustained exercise training sessions for individuals with paralyzed muscles.

Mammography test sets: reading location and prior images do not affect group performance.

AIM: To examine how the location where reading takes place and the availability of prior images can affect performance in breast test-set reading. MATERIALS AND METHODS: Under optimized viewing conditions, 10 expert screen readers each interpreted a reader-specific set of images containing 200 mammographic cases. Readers, randomly divided into two groups read images under one of two pairs of conditions: clinical read with prior images and laboratory read with prior images; laboratory read with prior images and laboratory read without prior images. Region-of-interest (ROI) figure-of-merit (FOM) was analysed using JAFROC software. Breast side-specific sensitivity and specificity were tested using Wilcoxon matched-pairs signed rank tests. Agreement between pairs of readings was measured using Kendall's coefficient of concordance. RESULTS: Group performances between test-set readings demonstrated similar ROI FOMs, sensitivity and specificity median values, and acceptable levels of agreement between pairs of readings were shown (W = 0.75-0.79, p < 0.001) for both pairs of reading conditions. On an individual reader level, two readers demonstrated significant decreases (p < 0.05) in ROI FOMs when prior images were unavailable. Reading location had an inconsistent impact on individual performance. CONCLUSION: Reading location and availability of prior images did not significantly alter group performance.

Wireless 'mini' multichannel intraluminal impedance-pH: what is the optimal design of a miniature wireless device?

Catheter-based methods for multichannel intraluminal impedance-pH monitoring are invasive and uncomfortable. The current alternative is a wireless system that clips to the esophageal mucosa, but which only measures pH. A shorter two-site wireless sensor that detects impedance and pH, and can be clipped to the esophagus, would be desirable. This study compares sensor positions and separations to determine the optimal configuration of a two-site wireless sensor. Records of 20 patients (10 on and 10 off proton pump inhibitor) who had ambulatory reflux testing with a multichannel intraluminal impedance-pH system (Sandhill Scientific Inc., Highlands Ranch, CO, USA) with six impedance and two pH sensors were reviewed. An investigator was blinded to four combinations of impedance channels plus pH. He read a 3-hour postprandial section from each of the combinations (total of 80 studies) and marked reflux episodes. Results were compared with his own interpretation of the full tracing. Two hundred and two total reflux episodes were analyzed, 113 acid (pH < 4) and 89 nonacid (pH > 4). Mean and median numbers of total reflux episodes were calculated. In the full study, the interpreter detected a mean of 10 reflux episodes per study. In the 5 cm and 7 cm, 3 cm and 7 cm, and 3 cm and 5 cm studies, the interpreter found a mean of 8.1, 11.1, and 9.8 reflux episodes per study, respectively. One-way analysis of variance yielded a P-value of 0.43. The trend of these preliminary findings suggests that the 3 cm and 5 cm site is the most sensitive and the 5 cm and 7 cm is the least, with the 3 cm and 7 cm site perhaps as the preferred location. The lack of a significant difference, at the very least, suggests that any of the 'mini' locations could be used. The small number of observations could have resulted in a Type II statistical error.

Can lower risk patients presenting with transient ischaemic attack be safely managed as outpatients?

This study aimed to examine outcome in low risk transient ischaemic attack (TIA) patients presenting to emergency departments (ED) in a regional Australian setting discharged on antiplatelet therapy with expedited neurology review. All patients presenting to Gosford or Wyong Hospital ED with TIA, for whom faxed referrals to the neurology department were received between October 2008 and July 2010, were included in this prospective cohort study. Classification of low risk was based on an age, blood pressure, clinical features, duration of symptoms and diabetes (ABCD2) score <4 and the absence of high risk features, including known carotid disease, crescendo TIA, or atrial fibrillation. Patients with ABCD2 scores > or =4 or with high risk features were discussed with the neurologist on call (a decision regarding discharge or admission was then made at the neurologist's discretion). Patients were investigated with a brain CT scan and/or CT angiography, routine pathology, and an electrocardiogram. All discharged patients were commenced on antiplatelet therapy and asked to follow up with their local medical officer within 7 days. The patients were contacted by the neurology department to arrange follow-up. Our primary outcome was the number of subsequent strokes occurring within 90 days. Of 200 discharged patients for whom referrals were received, three patients had a stroke within 90 days. None of these would have been prevented through hospitalisation. In conclusion, medical assessment, expedited investigation with immediate commencement of secondary prevention and outpatient neurology review may be a reasonable alternative to admission for low risk patients presenting to the ED with TIA.

Risk factors associated with reduced work productivity among people with chronic knee pain.

OBJECTIVE: To determine the burden and risk factors associated with reduced work productivity among people with chronic knee pain. METHOD: A longitudinal study, nested within a randomised controlled trial (RCT) evaluating the long-term effects of dietary supplements, was conducted among people with chronic knee pain in paid employment (n = 360). Participants recorded days off work (absenteeism) and reduced productivity while at work (presenteeism) for seven days every two months over a 12-month period in a study specific diary. Examined risk factors included knee pain severity, occupational group, radiographic disease severity, physical activity, body mass index (BMI), health-related quality of life (SF-12) and co-morbidity. RESULTS: Over the 12-month follow up period, 50 (14%) participants reported one or more days off work due to knee problems, while 283 (79%) reported reduced productivity while at work (presenteeism <100%). In multivariate analysis, the only significant risk factor for absenteeism was having an SF-12 Mental Component Summary (MCS) score <40 (OR: 2.49 [95% CI: 1.03-5.98]). Significant risk factors for presenteeism included; reporting an; SF-12 Physical Component Summary (PCS) score <50 (OR: 1.99 [95% CI: 1.05-3.76]), semi-manual labour (OR: 2.23 [1.09-4.59]) or manual labour (OR: 6.40 [1.44-28.35]) or a high maximum knee pain (4-6 out of 10) (OR: 2.29 [1.17-4.46]). CONCLUSIONS: This longitudinal study found that among this cohort of people with chronic knee pain, the burden of reduced work productivity is mainly attributable to presenteeism rather absenteeism. This study demonstrated that effective strategies to increase work productivity should focus on reducing knee pain or physical disability especially among workers in manual or semi-manual labour.

Establishing research priorities for Australian radiation therapists: what patient care priorities need to be addressed?

Much of the research conducted in radiotherapy focuses on technology advances; however, research may also be warranted in the area of patient care. The aims of this paper are to (1) identify patient care-related research priorities in radiation therapy and (2) describe similarities and differences in radiation therapists' responses to research priorities related to patient care by subgroups revealed through cluster analysis. A Delphi process was used, examining problems in research that radiation therapists face. Three hundred and seventy-four problems were identified. These were translated into 53 research areas which were then prioritised. Participant subgroups were identified using a hierarchical cluster procedure. Agreement and disagreement between subgroups for the subscale of 'Patient Care' were analysed with ANOVA and post hoc Scheffe multiple comparisons. The three subgroups had varying degrees of research interest in patient care. The groups agreed on the importance of research in relation to patient care in reducing and managing side effects, patient education and support, and treatment techniques. However, there was disagreement about the importance of conducting research into the role of radiation therapists, radiation therapists communicating and educating patients, and psychosocial support. Further research is warranted to determine radiotherapy patients' priorities and improve evidence-based practice.

Impact of biplane versus single-plane imaging on radiation dose, contrast load and procedural time in coronary angioplasty.

Coronary angioplasties can be performed with either single-plane or biplane imaging techniques. The aim of this study was to determine whether biplane imaging, in comparison to single-plane imaging, reduces radiation dose and contrast load and shortens procedural time during (i) primary and elective coronary angioplasty procedures, (ii) angioplasty to the main vascular territories and (iii) procedures performed by operators with various levels of experience. This prospective observational study included a total of 504 primary and elective single-vessel coronary angioplasty procedures utilising either biplane or single-plane imaging. Radiographic and clinical parameters were collected from clinical reports and examination protocols. Radiation dose was measured by a dose-area-product (DAP) meter intrinsic to the angiography system. Our results showed that biplane imaging delivered a significantly greater radiation dose (181.4+/-121.0 Gycm(2)) than single-plane imaging (133.6+/-92.8 Gycm(2), p<0.0001). The difference was independent of case type (primary or elective) (p = 0.862), vascular territory (p = 0.519) and operator experience (p = 0.903). No significant difference was found in contrast load between biplane (166.8+/-62.9 ml) and single-plane imaging (176.8+/-66.0 ml) (p = 0.302). This non-significant difference was independent of case type (p = 0.551), vascular territory (p = 0.308) and operator experience (p = 0.304). Procedures performed with biplane imaging were significantly longer (55.3+/-27.8 min) than those with single-plane (48.9+/-24.2 min, p = 0.010) and, similarly, were not dependent on case type (p = 0.226), vascular territory (p = 0.642) or operator experience (p = 0.094). Biplane imaging resulted in a greater radiation dose and a longer procedural time and delivered a non-significant reduction in contrast load than single-plane imaging. These findings did not support the commonly perceived advantages of using biplane imaging in single-vessel coronary interventional procedures.

SNP mapping and candidate gene sequencing in the class I region of the HLA complex: searching for multiple sclerosis susceptibility genes in Tasmanians.

This study is an extension to previously published work that has linked variation in the human leukocyte antigen (HLA) class I region with susceptibility to multiple sclerosis (MS) in Australians from the Island State of Tasmania. Single nucleotide polymorphism (SNP) mapping was performed on an 865-kb candidate region (D6S1683-D6S265) in 166 Tasmanian MS families, and seven candidate genes [ubiquitin D (UBD), olfactory receptor 2H3 (OR2H3), gamma-aminobutyric acid B receptor 1 (GABBR1), myelin oligodendrocyte glycoprotein (MOG), HLA-F, HLA complex group 4 (HCG4) and HLA-G] were resequenced. SNPs tagging the extended MS susceptibility haplotype were genotyped in an independent sample of 356 Australian MS trios and SNPs in the MOG gene were significantly over-transmitted to MS cases. We identified significant effects on MS susceptibility of HLA-A*2 (OR: 0.51; P = 0.05) and A*3 (OR: 2.85; P = 0.005), and two coding polymorphisms in the MOG gene (V145I: P = 0.01, OR: 2.2; V142L: P = 0.04, OR: 0.45) after full conditioning on HLA-DRB1. We have therefore identified plausible candidates for the causal MS susceptibility allele, and although not conclusive at this stage, our data provide suggestive evidence for multiple class I MS susceptibility genes.

Haplotypes of the interleukin 7 receptor alpha gene are correlated with altered expression in whole blood cells in multiple sclerosis.

IL7 regulates T cell survival, differentiation and proliferation. The alpha chain of its receptor, CD127, is polymorphic, and its haplotypes are associated with recovery from transplantation and with the autoimmune disease multiple sclerosis (MS), especially primary progressive MS (PPMS). We demonstrate that two CD127 haplotypes are highly associated with the proportion of the mRNA encoding the soluble isoform of CD127 (P

Familial effects on the clinical course of multiple sclerosis.

BACKGROUND: Familial factors influence susceptibility to multiple sclerosis (MS) but it is unknown whether there are additional effects on the natural history of the disease. METHOD: We evaluated 1,083 families with > or =2 first-degree relatives with MS for concordance of age at onset, clinical course, and disease severity and investigated transmission patterns of these clinical features in affected parent-child pairs. RESULTS: There is concordance for age at onset for all families (correlation coefficient 0.14; p < 0.001), as well as for affected siblings (correlation coefficient 0.15; p < 0.001), and affected parent-child pairs (correlation coefficient 0.12; p = 0.03) when each is evaluated separately. Concordance for year of onset is present among affected siblings (correlation coefficient 0.18; p < 0.001) but not the parent-child group (correlation coefficient 0.08; p = 0.15). The clinical course is similar between siblings (kappa 0.12; p < 0.001) but not affected parents and their children (kappa -0.04; p = 0.09). This influence on the natural history is present in all clinical subgroups of relapsing-remitting, and primary and secondary progressive MS, reflecting a familial effect on episodic and progressive phases of the disease. There is no concordance for disease severity within any of the considered family groups (correlation coefficients: all families analyzed together, 0.02, p = 0.53; affected sibling group, 0.02, p = 0.61; affected parent-child group, 0.02, p = 0.69). Furthermore, there are no apparent transmission patterns of any of the investigated clinical features in affected parent-child pairs and no evidence for anticipation or effects of genetic loading. CONCLUSION: Familial factors do not significantly affect eventual disease severity. However, they increase the probability of a progressive clinical course, either from onset or after a phase of relapsing remitting disease. The familial effect is more likely to reflect genetic than environmental conditions. The results are relevant for counseling patients and have implications for the design of studies seeking to identify factors that influence the natural history of the disease.

An investigation of polymorphisms in the 4q1 3.3-21.1 CXC chemokine gene cluster for association with multiple sclerosis in Australians.

Susceptibility to multiple sclerosis (MS) is believed to result from the complex interaction of a number of genes, each with modest effect. Vital to the migration of cells to sites of inflammation, including the central nervous system, are chemokines, many of which are implicated in MS pathogenesis. Most of the CXC chemokine genes are encoded in a cluster on chromosome 4q13.3-21.1, which has been identified in several genome-wide screens as being potentially associated with MS. We conducted a two-stage analysis to investigate the chemokine gene cluster for association with MS. Initially, we sequenced the chemokine genes in several DNA pools to identify common polymorphisms, and then genotyped selected SNPs in 373 Australian MS trio families. We found no evidence that the CXC chemokine gene cluster is genetically associated with MS. However, the existence of common variants conferring small risk factors or rare variants with significant risk cannot be excluded.

Gene expression and genotyping studies implicate the interleukin 7 receptor in the pathogenesis of primary progressive multiple sclerosis.

Multiple sclerosis (MS) is an enigmatic disease of the central nervous system resulting in sclerotic plaques with the pathological hallmarks of demyelination and axonal damage, which can be directly or indirectly orchestrated by cells from the peripheral circulation. The majority of patients with MS follow a relapsing-remitting course in the early stages of the disease (RRMS) but most ultimately enter a secondary progressive phase (SPMS). About 10% of patients follow a primary progressive course from the onset (PPMS). We measured gene expression in whole blood of people with and without chronic progressive MS (CPMS), PPMS and SPMS, to discover genes which may be differentially expressed in peripheral blood in active disease, and so identify pathologically significant genes and pathways; and we investigated genetic differences in the promoters of dysregulated genes encoded in genomic regions associated with MS. If SPMS and PPMS were independently compared to the controls, there was little overlap in the set of most dysregulated genes. Ribosomal protein genes, whose expression is usually associated with cell proliferation and activation, were dramatically over-represented in the set of most down-regulated genes in PPMS compared to SPMS (P < 10(-4), chi(2)). The T cell proliferation gene IL7R (CD127) was also underexpressed in PPMS, but was up-regulated in SPMS compared to the controls. One interleukin 7 receptor (IL7R) promoter single nucleotide polymorphism (SNP), -504 C, was undertransmitted in PPMS trios (P = 0.05, TDT), and carriers of this allele were under-represented in PPMS cases from two independent patient cohorts (combined P = 0.006, FE). The four known IL7R promoter haplotypes were shown to have similar expression levels in healthy controls, but not in CPMS (P < 0.01, t test). These data support the hypothesis that PPMS has significant pathogenetic differences from SPMS, and that IL7R may be a useful therapeutic target in PPMS.

Hyperbaric oxygen therapy for multiple sclerosis.

BACKGROUND: Multiple Sclerosis (MS) is a chronic, recurrent and progressive illness with no cure. On the basis of speculative pathophysiology, it has been suggested that Hyperbaric Oxygen Therapy (HBOT) may slow or reverse the progress of the disease. OBJECTIVES: The object of this review was to evaluate the efficacy and safety of HBOT in the treatment of MS. SEARCH STRATEGY: We searched the Cochrane MS Group trials register (July 2002), the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 2, 2002), MEDLINE (January 1966 to October 2002) and the National Library of Medicine (NLM) database (July 2002), along with specialised hyperbaric resources and handsearching of relevant journals and proceedings. SELECTION CRITERIA: All randomised, controlled trials involving a comparison between HBOT and a sham therapy in MS were evaluated. DATA COLLECTION AND ANALYSIS: Two reviewers independently appraised all comparative trials identified, extracted data and scored them for methodological quality. MAIN RESULTS: We identified ten reports of nine trials that satisfied selection criteria (504 participants in total). Two trials produced generally positive results, while the remaining seven reported generally no evidence of a treatment effect. None of our three a priori subgroup analyses placed these two trials in the same group and were therefore unable to account for this difference. Three analyses (of 21) did indicate some benefit. For example, the mean Expanded Disability Status Scale (EDSS) at 12 months was improved in the HBOT group (group mean reduction in EDSS compared to sham -0.85 of a point, 95% confidence interval -1.28 to -0.42, P = 0.0001). Only the two generally positive trials reported on this outcome at this time (16% of the total participants in this review). REVIEWER'S CONCLUSIONS: We found no consistent evidence to confirm a beneficial effect of hyperbaric oxygen therapy for the treatment of multiple sclerosis and do not believe routine use is justified. The small number of analyses suggestive of benefit are isolated, difficult to ascribe with biological plausibility and would need to be confirmed in future well-designed trials. Such trials are not, in our view, justified by this review.

A genome-wide screen for linkage disequilibrium in Australian HLA-DRB1*1501 positive multiple sclerosis patients.

The association of multiple sclerosis with alleles/haplotypes from the HLA region on chromosome 6p21 is well established although the remainder of the genome remains relatively unexplored. We have completed a genome-wide screen for linkage disequilibrium in a cohort of Australian multiple sclerosis patients positive for HLA-DRB1*1501. A total of 4346 microsatellite markers provided through the "Genetic Analysis of Multiple sclerosis in EuropeanS" (GAMES) collaborative were analysed in DNA separately pooled from cases (n=217) and controls (n=187). Associations were found in four genomic regions (12q15, 16p13, 18p11 and 19q13) previously identified in linkage genome screens. Three additional regions of novel association were also identified (11q12, 11q23 and 14q21). Further analysis of these regions is required to establish whether the associations observed are due to epistatic interaction with the HLA locus.