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1.  Oral and Gastric Helicobacter Pylori: Effects and Associations 
PLoS ONE  2015;10(5):e0126923.
This study consisted in the comparison of the prevalence of Helicobacter pylori (H. pylori) present in the stomach and in saliva of a sample of Portuguese adolescents and the assessment of the association between H. pylori infection with socio-demographic variables and prevalence of dental caries.
Materials and Methods
A cross-sectional study was designed including a sample of 447 adolescents aged 12 to 19 years old, attending a public school in Sátão, Portugal. A questionnaire about socio-demographic variables and oral health behaviors was applied. Gastric H. pylori infection was determined using the urease breath test (UBT). Saliva collection was obtained and DNA was extracted by Polymerase Chain Reaction (PCR) in order to detect the presence of oral H. pylori.
The prevalence of gastric H. pylori detected by UBT was 35.9%. Within the adolescents with a gastric UBT positive, only 1.9% were positive for oral H. pylori. The presence of gastric H. pylori was found to be associated with age (>15years, Odds ratio (OR)=1.64,95%CI=1.08-2.52), residence area (urban,OR=1.48,95%CI=1.03-2.29) and parents´ professional situation (unemployed,OR=1.22,95%CI=1.02-1.23). Among those with detected dental caries during the intra-oral observation, 37.4% were positive for gastric H. pylori and 40.2% negative for the same bacterial strain (p=0.3).
The oral cavity cannot be considered a reservoir for infection of H. pylori. Gastric H. pylori infection was found to be associated with socio-demographic variables such as age, residence area and socioeconomic status.
PMCID: PMC4444322  PMID: 26010595
2.  Efficacy and safety of paracetamol for spinal pain and osteoarthritis: systematic review and meta-analysis of randomised placebo controlled trials 
Objective To investigate the efficacy and safety of paracetamol (acetaminophen) in the management of spinal pain and osteoarthritis of the hip or knee.
Design Systematic review and meta-analysis.
Data sources Medline, Embase, AMED, CINAHL, Web of Science, LILACS, International Pharmaceutical Abstracts, and Cochrane Central Register of Controlled Trials from inception to December 2014.
Eligibility criteria for selecting studies Randomised controlled trials comparing the efficacy and safety of paracetamol with placebo for spinal pain (neck or low back pain) and osteoarthritis of the hip or knee.
Data extraction Two independent reviewers extracted data on pain, disability, and quality of life. Secondary outcomes were adverse effects, patient adherence, and use of rescue medication. Pain and disability scores were converted to a scale of 0 (no pain or disability) to 100 (worst possible pain or disability). We calculated weighted mean differences or risk ratios and 95% confidence intervals using a random effects model. The Cochrane Collaboration’s tool was used for assessing risk of bias, and the GRADE approach was used to evaluate the quality of evidence and summarise conclusions.
Results 12 reports (13 randomised trials) were included. There was “high quality” evidence that paracetamol is ineffective for reducing pain intensity (weighted mean difference −0.5, 95% confidence interval −2.9 to 1.9) and disability (0.4, −1.7 to 2.5) or improving quality of life (0.4, −0.9 to 1.7) in the short term in people with low back pain. For hip or knee osteoarthritis there was “high quality” evidence that paracetamol provides a significant, although not clinically important, effect on pain (−3.7, −5.5 to −1.9) and disability (−2.9, −4.9 to −0.9) in the short term. The number of patients reporting any adverse event (risk ratio 1.0, 95% confidence interval 0.9 to 1.1), any serious adverse event (1.2, 0.7 to 2.1), or withdrawn from the study because of adverse events (1.2, 0.9 to 1.5) was similar in the paracetamol and placebo groups. Patient adherence to treatment (1.0, 0.9 to 1.1) and use of rescue medication (0.7, 0.4 to 1.3) was also similar between groups. “High quality” evidence showed that patients taking paracetamol are nearly four times more likely to have abnormal results on liver function tests (3.8, 1.9 to 7.4), but the clinical importance of this effect is uncertain.
Conclusions Paracetamol is ineffective in the treatment of low back pain and provides minimal short term benefit for people with osteoarthritis. These results support the reconsideration of recommendations to use paracetamol for patients with low back pain and osteoarthritis of the hip or knee in clinical practice guidelines.
Systematic review registration PROSPERO registration number CRD42013006367.
PMCID: PMC4381278  PMID: 25828856
3.  Effectiveness of Surgery for Lumbar Spinal Stenosis: A Systematic Review and Meta-Analysis 
PLoS ONE  2015;10(3):e0122800.
The management of spinal stenosis by surgery has increased rapidly in the past two decades, however, there is still controversy regarding the efficacy of surgery for this condition. Our aim was to investigate the efficacy and comparative effectiveness of surgery in the management of patients with lumbar spinal stenosis.
Electronic searches were performed on MEDLINE, EMBASE, AMED, CINAHL, Web of Science, LILACS and Cochrane Library from inception to November 2014. Hand searches were conducted on included articles and relevant reviews. We included randomised controlled trials evaluating surgery compared to no treatment, placebo/sham, or to another surgical technique in patients with lumbar spinal stenosis. Primary outcome measures were pain, disability, recovery and quality of life. The PEDro scale was used for risk of bias assessment. Data were pooled with a random-effects model, and the GRADE approach was used to summarise conclusions.
Nineteen published reports (17 trials) were included. No trials were identified comparing surgery to no treatment or placebo/sham. Pooling revealed that decompression plus fusion is not superior to decompression alone for pain (mean difference –3.7, 95% confidence interval –15.6 to 8.1), disability (mean difference 9.8, 95% confidence interval –9.4 to 28.9), or walking ability (risk ratio 0.9, 95% confidence interval 0.4 to 1.9). Interspinous process spacer devices are slightly more effective than decompression plus fusion for disability (mean difference 5.7, 95% confidence interval 1.3 to 10.0), but they resulted in significantly higher reoperation rates when compared to decompression alone (28% v 7%, P < 0.001). There are no differences in the effectiveness between other surgical techniques for our main outcomes.
The relative efficacy of various surgical options for treatment of spinal stenosis remains uncertain. Decompression plus fusion is not more effective than decompression alone. Interspinous process spacer devices result in higher reoperation rates than bony decompression.
PMCID: PMC4378944  PMID: 25822730
4.  Clinicians’ views on factors that trigger a sudden onset of low back pain 
European Spine Journal  2013;23(3):512-519.
Little is known about what triggers an episode of low back pain (LBP) in those presenting to primary care. Previous studies of risk factors have focused on specific occupational settings and work conditions. No study has asked primary care clinicians to consider what triggers an episode of sudden-onset LBP in patients presenting to them for care. The purpose of this study, therefore, was to describe the short- and long-term factors that primary care clinicians consider important in triggering a sudden episode of acute LBP.
One hundred and thirty-one primary care clinicians who were recruiting patients with LBP to a large observational study were invited to participate. A questionnaire was designed to obtain information about the clinician’s characteristics, profession and clinical experience. We also asked clinicians to nominate the five short- and five long-term exposure factors, most likely to trigger a sudden episode of acute LBP, based on their experience. Descriptive statistics and frequency distributions were used to describe clinician’s characteristics and the frequencies of the main risk factor categories were reported.
Based on the views of 103 primary care clinicians, biomechanical risk factors appear to be the most important short-term triggers (endorsed by 89.3 % of clinicians) and long-term triggers (endorsed by 54.2 % of clinicians) for a sudden episode of acute LBP. Individual risk factors were endorsed by 39 % of clinicians as important long-term triggers, while only 6.4 % of clinicians considered them important short-term triggers. Other risk factors, such as psychological/psychosocial and genetic factors, were not commonly endorsed as risk factors for an episode of LBP by primary care clinicians.
This study shows that primary care clinicians believe that biomechanical risk factors are the most important short-term triggers, while biomechanical and individual risk factors are the most important long-term triggers for a sudden onset of LBP. However, other risk factors, such as psychological/psychosocial and genetic, were not commonly endorsed as risk factors for an episode of LBP by primary care clinicians. Results of this study are based on primary care clinicians’ views and further investigation is needed to test the validity of these suggested risk factors.
PMCID: PMC3940811  PMID: 24318162
Low back pain; Primary care; Risk factors; Observational; Epidemiology
5.  Prognosis of chronic low back pain in patients presenting to a private community-based group exercise program 
European Spine Journal  2013;23(1):113-119.
To examine the prognosis and prognostic factors for patients with chronic low back pain presenting to a private, community-based, group exercise program.
A total of 118 consecutive patients with chronic LBP were recruited. Baseline assessments included socio-demographic characteristics, back pain history and clinical examination findings. Primary outcome measures were pain intensity and disability at 3, 6 and 12 months. Potential prognostic factors to predict pain intensity and disability at 12 months were assessed using a multivariate regression model.
112 (95 %) participants were followed up at 12 months. The majority of participants were female (73 %), had high educational levels (82 %) and resided in suburbs with a high socio-economic status (99 %). Pain intensity improved markedly during the first 6 months (35 %) with further minimal reductions up to 12 months (39 %). Interestingly, disability improved to a greater degree than pain (48 % improvement at 6 months) and continued to improve throughout the 12 months (60 %). Baseline pain intensity accounted for 10 % of the variance in the 1 year pain outcomes. Duration of current episode, baseline disability and educational level accounted for 15 % of the variation in disability at 12 months.
During a period of 12 months, patients with chronic LBP presenting to a private, community-based, group exercise program improved markedly, with greater improvements in disability than pain. The predictors investigated accounted for only 10 and 15 % of pain and disability outcomes, respectively.
PMCID: PMC3897833  PMID: 23793557
Chronic low back pain; Prognosis; Disability; Outcomes
6.  Self-reported chronic pain is associated with physical performance in older people leaving aged care rehabilitation 
The impact of pain on the physical performance of patients in aged care rehabilitation is not known. The study sought to assess 1) the prevalence of pain in older people being discharged from inpatient rehabilitation; 2) the association between self-reported pain and physical performance in people being discharged from inpatient rehabilitation; and 3) the association between self-reported pain and physical performance in this population, after adjusting for potential confounding factors.
This was an observational cross-sectional study of 420 older people at two inpatient aged care rehabilitation units. Physical performance was assessed using the Lower Limb Summary Performance Score. Pain was assessed with questions about the extent to which participants were troubled by pain, the duration of symptoms, and the impact of chronic pain on everyday activity. Depression and the number of comorbidities were assessed by questionnaire and medical file audit. Cognition was assessed with the Mini-Mental State Examination.
Thirty percent of participants reported chronic pain (pain lasting more than 3 months), and 17% reported that this pain interfered with daily activities to a moderate or greater extent. Chronic pain (P=0.013) and chronic pain affecting daily activities (P<0.001) were associated with a poorer Lower Limb Summary Performance Score. The relationship between chronic pain affecting daily activities and Lower Limb Summary Performance Score remained significant (P=0.001) after adjusting for depression, age, comorbidities, and Mini-Mental State Examination score. This model explained 10% of the variability in physical performance.
One-third of participants reported chronic pain, and close to one-fifth reported that this pain interfered with daily activities. Chronic pain was associated with impaired physical performance, and this relationship persisted after adjusting for likely confounding factors.
PMCID: PMC3921084  PMID: 24523583
pain; older people; physical performance; rehabilitation
7.  The Bruininks-Oseretsky Test of Motor Proficiency-Short Form is reliable in children living in remote Australian Aboriginal communities 
BMC Pediatrics  2013;13:135.
The Lililwan Project is the first population-based study to determine Fetal Alcohol Spectrum Disorders (FASD) prevalence in Australia and was conducted in the remote Fitzroy Valley in North Western Australia. The diagnostic process for FASD requires accurate assessment of gross and fine motor functioning using standardised cut-offs for impairment. The Bruininks-Oseretsky Test of Motor Proficiency, Second Edition (BOT-2) is a norm-referenced assessment of motor function used worldwide and in FASD clinics in North America. It is available in a Complete Form with 53 items or a Short Form with 14 items. Its reliability in measuring motor performance in children exposed to alcohol in utero or living in remote Australian Aboriginal communities is unknown.
A prospective inter-rater and test-retest reliability study was conducted using the BOT-2 Short Form. A convenience sample of children (n = 30) aged 7 to 9 years participating in the Lililwan Project cohort (n = 108) study, completed the reliability study. Over 50% of mothers of Lililwan Project children drank alcohol during pregnancy. Two raters simultaneously scoring each child determined inter-rater reliability. Test-retest reliability was determined by assessing each child on a second occasion using predominantly the same rater. Reliability was analysed by calculating Intra-Class correlation Coefficients, ICC(2,1), Percentage Exact Agreement (PEA) and Percentage Close Agreement (PCA) and measures of Minimal Detectable Change (MDC) were calculated.
Thirty Aboriginal children (18 male, 12 female: mean age 8.8 years) were assessed at eight remote Fitzroy Valley communities. The inter-rater reliability for the BOT-2 Short Form score sheet outcomes ranged from 0.88 (95%CI, 0.77 – 0.94) to 0.92 (95%CI, 0.84 – 0.96) indicating excellent reliability. The test-retest reliability (median interval between tests being 45.5 days) for the BOT-2 Short Form score sheet outcomes ranged from 0.62 (95%CI, 0.34 – 0.80) to 0.73 (95%CI, 0.50 – 0.86) indicating fair to good reliability. The raw score MDC was 6.12.
The BOT-2 Short Form has acceptable reliability for use in remote Australian Aboriginal communities and will be useful in determining motor deficits in children exposed to alcohol prenatally. This is the first known study evaluating the reliability of the BOT-2 Short Form, either in the context of assessment for FASD or in Aboriginal children.
PMCID: PMC3844452  PMID: 24010634
Fetal alcohol spectrum disorders; Fetal alcohol syndrome (FAS); Alcohol related neurodevelopmental disorder; Australian Aborigine; Maternal use of alcohol; School-aged children; Reproducibility of results; Culture; Motor skills; Child development
8.  A literature review reveals that trials evaluating treatment of non-specific low back pain use inconsistent criteria to identify serious pathologies and nerve root involvement 
The broad aim of this study was to assess the homogeneity of patients included in trials of non-specific low back pain (NSLBP). To do this, we investigated the consistency and clarity of criteria used to identify and exclude participants with serious pathologies and nerve root compromise in randomized controlled trials, investigating interventions for NSLBP.
We searched Medline database for randomized controlled trials of low back pain (LBP). published between 2000 and 2009. We then randomly selected and screened trials for inclusion until we had 50 eligible trials. Data were extracted on the criteria used to identify cases of serious conditions (e.g. cancer, fracture) and nerve root involvement.
The majority of papers (35/50) explicitly excluded patients with serious pathology. However, the terminology used and examples given were highly variable. Nerve root involvement was an exclusion criterion in the majority but not all studies. The criteria used for excluding patients with nerve root involvement varied greatly between studies. The most common criteria were ‘motor, sensory or reflex changes’ (nine studies), followed by ‘pain radiating below the knee’ (five studies) and ‘reduced straight leg raise which reproduces leg pain’ (five studies). In half of the included studies, the criteria used, while alluding to nerve root involvement, were not explained adequately for us to determine the types of patients included or excluded.
The inconsistent and unclear criteria used to identify cases of serious pathology and nerve root compromise means that published trials of LBP likely include heterogeneous patient populations. This trait limits our ability to make comparisons across trials or pool studies. Standardization and consensus is important for future research.
PMCID: PMC3360485  PMID: 23633884
Low back pain; Sciatica; Nerve root compromise; Red flags
9.  Development of a reliable questionnaire to assist in the diagnosis of fetal alcohol spectrum disorders (FASD) 
BMC Pediatrics  2013;13:33.
A battery of clinical assessments was used in the Lililwan* Project, Australia’s first population-based Fetal Alcohol Spectrum Disorders (FASD) prevalence study, conducted in the remote Fitzroy Valley, Western Australia. One objective was to develop and assess test-retest reliability of an acceptable questionnaire for collecting health information in remote Aboriginal communities feasible for use in the Lililwan Project.
A questionnaire was developed by paediatricians to assist in diagnosis of FASD. Content was based on a literature review of FASD diagnostic criteria, existing questionnaires and risk factors for FASD and birth defects. Aboriginal community members, including qualified Aboriginal language interpreters, adapted the questionnaire to ensure language and cultural components were appropriate for use in the Fitzroy Valley. Locally developed pictorial aids were used for gathering accurate information on alcohol use. Aboriginal ‘community navigators’ assisted researchers to translate the questions into Kimberley Kriol or local Aboriginal languages depending on participant preference.
A subset of 14 questions was assessed for test-retest reliability in 30 parents/carers of children in the Lililwan Project cohort, who were interviewed by one rater using the entire questionnaire, then by a second rater who repeated 14 critical questions at least 6 hours later.
The full questionnaire contained 112 items and took 50 minutes to administer. For a subset of 14 items from the full questionnaire percent exact agreement between raters ranged from 59-100%, and was below 70% for only 1 question. Test-retest reliability was excellent (Kappa 0.81-1.00) for 5 items, substantial (Kappa 0.61-0.80) for 5 items, and moderate, fair or slight (Kappa ≤0.60) for the remaining 4 items tested. Test-retest reliability for questions relating to alcohol use in pregnancy was excellent. When questions had moderate, fair or slight agreement, information was obtained from alternate sources e.g. medical records. Qualitative feedback from parents/carers confirmed acceptability of the questionnaire.
This questionnaire had acceptable test-retest reliability and could be used to collect demographic, socio-cultural and biomedical information relevant to the diagnosis of FASD in Aboriginal communities throughout Australia and elsewhere. Community input is crucial when developing and administering questionnaires for use in cross-cultural contexts.
*Lililwan is a Kimberley Kriol word meaning ‘all the little ones’. Kimberley Kriol is the main language spoken by Aboriginal people in the Fitzroy Valley.
PMCID: PMC3680181  PMID: 23496974
Fetal alcohol syndrome (FAS); Fetal alcohol spectrum disorders (FASD); Aboriginal and Torres Strait Islander; Indigenous; Questionnaire development; Diagnosis; Reliability testing; Reproducibility of results; Test-retest; Percent exact agreement
10.  A systematic review of the unit costs of allied health and community services used by older people in Australia 
An economic evaluation of interventions for older people requires accurate assessment of costing and consideration of both acute and long-term services. Accurate information on the unit cost of allied health and community services is not readily available in Australia however. This systematic review therefore aims to synthesise information available in the literature on the unit costs of allied health and community services that may be utilised by an older person living in Australia.
A comprehensive search of Medline, Embase, CINAHL, Google Scholar and Google was undertaken. Specialised economic databases were also reviewed. In addition Australian Government Department websites were inspected. The search identified the cost of specified allied health services including: physiotherapy, occupational therapy, dietetics, podiatry, counselling and home nursing. The range of community services included: personal care, meals on wheels, transport costs and domestic services. Where the information was not available, direct contact with service providers was made.
The number of eligible studies included in the qualitative synthesis was fourty-nine. Calculated hourly rates for Australian allied health services were adjusted to be in equivalent currency and were as follows as follows: physiotherapy $157.75, occupational therapy $150.77, dietetics $163.11, psychological services $165.77, community nursing $105.76 and podiatry $129.72.
Utilisation of the Medicare Benefits Scheduled fee as a broad indicator of the costs of services, may lead to underestimation of the real costs of services and therefore to inaccuracies in economic evaluation.
PMCID: PMC3586358  PMID: 23421756
Unit costs; Allied health services; Community services
11.  How big does the effect of an intervention have to be? Application of two novel methods to determine the smallest worthwhile effect of a fall prevention programme: a study protocol 
BMJ Open  2013;3(2):e002355.
This project concerns the identification of the smallest worthwhile effect (SWE) of exercise-based programmes to prevent falls in older people. The SWE is the smallest effect that justifies the costs, risks and inconveniences of an intervention and is used to inform the design and interpretation of systematic reviews and randomised clinical trials.
Methods and analysis
This study will comprise two different methodological approaches: the benefit-harm trade-off method and the discrete choice experiment to estimate the SWE of exercise interventions to prevent falls in older people. In the benefit-harm trade-off method, hypothetical scenarios with the benefits, costs, risks and inconveniences associated with the intervention will be presented to each participant. Then, assuming a treatment effect of certain magnitude, the participant will be asked if he or she would choose to have the intervention. The size of the hypothetical benefit will be varied up and down until it is possible to identify the SWE for which the participant would choose to have the intervention. In the discrete choice experiment, the same attributes (benefits, costs, risks and inconveniences) with varying levels will be presented as choice sets, and participants will be asked to choose between these choice sets. With this approach, we will determine the probability that a person will consider the effects of an intervention to be worthwhile, given the particular costs, risks and inconveniences. For each of the two approaches, participants will be interviewed in person and on different occasions. A subsample of the total cohort will participate in both interviews.
Ethics and dissemination
This project has received Ethics Approval from the University of Sydney Human Ethics Committee (Protocol number: 14404). Findings will be disseminated through conference presentations, seminars and peer-reviewed scientific journals.
PMCID: PMC3586108  PMID: 23388197
Rehabilitation Medicine; Geriatric Medicine; Preventive Medicine
12.  An Unusual Endoscopic Image of a Submucosal Angiodysplasia 
Obscure gastrointestinal bleeding is responsible for 2–10% of the cases of digestive bleeding. Angiodysplasia is the most common cause. The authors report a case of a 70-year-old female patient admitted to our Gastrointestinal Intensive Care Unit with a significant digestive bleeding. Standard upper and lower endoscopy showed no abnormalities, and we decided to perform a capsule enteroscopy that revealed a submucosal nodule with active bleeding in the jejunum. An intraoperative enteroscopy confirmed the presence of a small submucosal lesion with a central ulceration, and subsequently a segmental enterectomy was performed. Surprisingly, the histopathological diagnosis was angiodysplasia. The patient remains well after a two-year period of follow-up. We present this case of obscure/overt gastrointestinal bleeding to emphasize the role of capsule and intraoperative enteroscopy in the evaluation of these situations, and because of the unusual endoscopic appearance of the angiodysplasia responsible for the hemorrhage.
PMCID: PMC3459249  PMID: 23050173
13.  Spatial Coupling of mTOR and Autophagy Augments Secretory Phenotypes 
Science (New York, N.Y.)  2011;332(6032):966-970.
Protein synthesis and autophagic degradation are regulated in an opposite manner by mammalian target of rapamycin (mTOR), whereas under certain conditions it would be beneficial if they occured in unison to handle rapid protein turnover. We observed a distinct cellular compartment at the trans-side of the Golgi apparatus, the ‘TOR-autophagy spatial coupling compartment’ (TASCC), where (auto)lysosomes and mTOR accumulated during Ras-induced senescence. mTOR recruitment to the TASCC was amino acid- and Rag guanosine triphosphatase (GTPase)-dependent, and disruption of mTOR localization to the TASCC suppressed interleukin-6/8 synthesis. TASCC-formation was observed during macrophage differentiation and in glomerular podocytes; both displayed increased protein secretion. The spatial coupling of cells’ catabolic and anabolic machinery could augment their respective functions and facilitate the mass synthesis of secretory proteins.
PMCID: PMC3426290  PMID: 21512002
14.  The Lililwan Project: study protocol for a population-based active case ascertainment study of the prevalence of fetal alcohol spectrum disorders (FASD) in remote Australian Aboriginal communities 
BMJ Open  2012;2(3):e000968.
Anecdotal reports suggest that high-risk drinking in pregnancy is common in some remote Australian communities. Alcohol is teratogenic and may cause a range of lifelong conditions termed ‘fetal alcohol spectrum disorders’ (FASD). Australia has few diagnostic services for FASD, and prevalence of these neurodevelopmental disorders remains unknown. In 2009, Aboriginal leaders in the remote Fitzroy Valley in North Western Australia identified FASD as a community priority and initiated the Lililwani Project in partnership with leading research organisations. This project will establish the prevalence of FASD and other health and developmental problems in school-aged children residing in the Fitzroy Valley, providing data to inform FASD prevention and management.
Methods and analysis
This is a population-based active case ascertainment study of all children born in 2002 and 2003 and residing in the Fitzroy Valley. Participants will be identified from the Fitzroy Valley Population Project and Communicare databases. Parents/carers will be interviewed using a standardised diagnostic questionnaire modified for local language and cultural requirements to determine the demographics, antenatal exposures, birth outcomes, education and psychosocial status of each child. A comprehensive interdisciplinary health and neurodevelopmental assessment will be performed using tests and operational definitions adapted for the local context. Internationally recognised diagnostic criteria will be applied to determine FASD prevalence. Relationships between pregnancy exposures and early life trauma, neurodevelopmental, health and education outcomes will be evaluated using regression analysis. Results will be reported according to STROBE guidelines for observational studies.
Ethics and dissemination
Ethics approval has been granted by the University of Sydney Human Research Ethics Committee, the Western Australian Aboriginal Health Information and Ethics Committee, the Western Australian Country Health Service Board Research Ethics Committee and the Kimberley Aboriginal Health Planning Forum Research Sub-committee. Results will be disseminated widely through peer-reviewed manuscripts, reports, conference presentations and the media.
Article summary
Article focus
To establish the need for prevalence data on FASD in remote Australia and for improved awareness and diagnosis of FASD.
To describe the protocol used in Australia's first population-based study of FASD prevalence using active case ascertainment in remote Aboriginal communities.
To demonstrate a process of community consultation and clinical research that respects the priorities, language and culture of Aboriginal communities.
Key messages
Accurate prevalence data on FASD and other health and developmental outcomes will inform prevention, service provision and policy in child health, education and justice.
This research will provide immediate and direct benefits to participants and the broader community, including a feasible and transferable model of FASD diagnosis and a model for culturally responsive research with Aboriginal communities.
Strengths and limitations of this study
The study was a response to a local community initiative and followed extensive community consultation.
The population-based active method of case ascertainment will provide the most accurate prevalence data for diagnoses on the entire FASD spectrum and other health and developmental outcomes.
Standardised and locally developed clinical assessments whose interpretation is less biased by culture and language have been chosen carefully with cross-cultural considerations in mind and are considered valid for the purpose of the study.
There are no normative data for Aboriginal children for the assessments used in the study.
Study findings may not generalise to all children born in the Fitzroy Valley following the introduction of community-led alcohol restrictions in 2007, after which time FASD prevalence may have decreased.
PMCID: PMC3346942  PMID: 22556161
15.  The basement membrane of hair follicle stem cells is a muscle cell niche 
Cell  2011;144(4):577-589.
The hair follicle bulge in the epidermis associates with the arrector pili muscle (APM) that is responsible for piloerection (commonly called "goosebumps"). We show that deposition of nephronectin into the basement membrane by bulge stem cells mediates selective adhesion of α8β1 integrin-expressing mesenchymal cells, including APM progenitors. Nephronectin induces α8 integrin-positive cells to upregulate smooth muscle markers. In nephronectin-null skin, the number of APM is reduced and those that form insert above the bulge, where there is compensatory upregulation of the nephronectin family member EGFL6. Deletion of α8 integrin also abolishes the selectivity of APM anchorage to the bulge. Nephronectin is a Wnt target gene; epidermal β-catenin activation upregulates epidermal nephronectin and dermal α8 integrin expression. We conclude that by expressing nephronectin bulge stem cells provide a smooth muscle cell niche and act as tendon cells for the APM. The results also reveal a functional role for basement membrane heterogeneity in tissue patterning.
PMCID: PMC3056115  PMID: 21335239
16.  Triggers for an episode of sudden onset low back pain: study protocol 
Most research on risk factors for low back pain has focused on long term exposures rather than factors immediately preceding the onset of low back pain. The aim of this study is to quantify the transient increase in risk of a sudden episode of low back pain associated with acute exposure to a range of common physical and psychological factors.
This study uses a case-crossover design. One thousand adults with a sudden onset of low back pain presenting to primary care clinicians will be recruited. Basic demographic and clinical information including exposure to putative triggers will be collected using a questionnaire. These triggers include exposure to hazardous manual tasks, physical activity, a slip/trip or fall, consumption of alcohol, sexual activity, being distracted, and being fatigued or tired. Exposures in the case window (0-2 hours from the time when participants first notice their back pain) will be compared to exposures in two control time-windows (one 24-26 hours and another 48-50 hours before the case window).
The completion of this study will provide the first-research based estimates of the increase in risk of a sudden episode of acute low back pain associated with transient exposure to a range of common factors thought to trigger low back pain.
PMCID: PMC3292970  PMID: 22273001
17.  The patient-specific functional scale is more responsive than the Roland Morris disability questionnaire when activity limitation is low 
European Spine Journal  2010;20(1):79-86.
The primary objective of this study was to determine which questionnaire, the Roland Morris disability questionnaire (RMDQ) or the patient-specific functional scale (PSFS), was better at detecting change in activity limitation in a large cohort of patients with low back pain undergoing rehabilitation. A secondary aim was to determine if the responsiveness of the questionnaires was influenced by the patient’s level of activity limitation at baseline. Responsiveness statistics, including effect size statistics, Pearson’s r correlations and receiver operative characteristic (ROC) curve analysis were used to determine ability to detect change in activity limitation on 831 patients with low back pain. Data were analysed at two time points; directly after treatment (termed short-term) and several weeks post-treatment (termed mid-term). The data were subsequently re-analysed on sub-sets of the full cohort according to the level of activity limitation from RMDQ baseline scores. In the total cohort we found that the PSFS was more responsive than the RMDQ; however, in the subgroup with high activity limitation this pattern was not observed. This is true for time points up to 6 months post-treatment. In conclusion, the RMDQ and PSFS both demonstrate good responsiveness according to the definitions given in previous guidelines. The PSFS is more responsive than the RMDQ for patients with low levels of activity limitation but not for patients with high levels of activity limitation.
PMCID: PMC3036014  PMID: 20628767
Back pain; Disability; Activity limitation; Rehabilitation; Responsiveness
18.  Back Complaints in the Elders (BACE); design of cohort studies in primary care: an international consortium 
Although back complaints are common among older people, limited information is available in the literature about the clinical course of back pain in older people and the identification of older persons at risk for the transition from acute back complaints to chronic back pain.
The aim of this study is to assess the course of back complaints and identify prognostic factors for the transition from acute back complaints to chronic back complaints in older people who visit a primary health care physician.
The design is a prospective cohort study with one-year follow-up. There will be no interference with usual care. Patients older than 55 years who consult a primary health care physician with a new episode of back complaints will be included in this study.
Data will be collected using a questionnaire, physical examination and X-ray at baseline, and follow-up questionnaires after 6 weeks and 3, 6, 9 and 12 months.
The study 'Back Complaints in the Elders' (BACE) will take place in different countries: starting in the Netherlands, Brazil and Australia. The research groups collaborate in the BACE consortium. The design and basic objectives of the study will be the same across the studies.
This consortium is a collaboration between different research groups, aiming to provide insight into the course of back complaints in older people and to identify prognostic factors for the transition from acute back complaints to chronic back complaints in older persons. The BACE consortium allows to investigate differences between older people with back complaints and the health care systems in the different countries and to increase the statistical power by enabling meta-analyses using the individual patient data. Additional research groups worldwide are invited to join the BACE consortium.
PMCID: PMC3182961  PMID: 21854620
19.  TNF-α Regulates the Effects of Irradiation in the Mouse Bone Marrow Microenvironment 
PLoS ONE  2010;5(2):e8980.
Secondary bone marrow (BM) myelodysplastic syndromes (MDS) are increasingly common, as a result of radio or chemotherapy administered to a majority of cancer patients. Patients with secondary MDS have increased BM cell apoptosis, which results in BM dysfunction (cytopenias), and an increased risk of developing fatal acute leukemias. In the present study we asked whether TNF-α, known to regulate cell apoptosis, could modulate the onset of secondary MDS.
Principal Findings
We show that TNF-α is induced by irradiation and regulates BM cells apoptosis in vitro and in vivo. In contrast to irradiated wild type (WT) mice, TNF-α deficient (TNF-α KO) mice or WT mice treated with a TNF-α-neutralizing antibody were partially protected from the apoptotic effects of irradiation. Next we established a 3-cycle irradiation protocol, in which mice were sub-lethally irradiated once monthly over a 3 month period. In this model, irradiated WT mice presented loss of microsatellite markers on BM cells, low white blood cell (WBC) counts, reduced megakaryocyte (MK) and platelet levels (thrombocytopenia) and macrocytic anemia, phenoypes that suggest the irradiation protocol resulted in BM dysfunction with clinical features of MDS. In contrast, TNF-α KO mice were protected from the irradiation effects: BM cell apoptosis following irradiation was significantly reduced, concomitant with sustained BM MK numbers and absence of other cytopenias. Moreover, irradiated WT mice with long term (≥5 months) BM dysfunction had increased BM angiogenesis, MMPs and VEGF and NFkB p65, suggestive of disease progression.
Taken together, our data shows that TNF-α induction following irradiation modulates BM cell apoptosis and is a crucial event in BM dysfunction, secondary MDS onset and progression.
PMCID: PMC2813873  PMID: 20126546
20.  Applying Joint Mobilization at Different Cervical Vertebral Levels does not Influence Immediate Pain Reduction in Patients with Chronic Neck Pain: A Randomized Clinical Trial 
The aim of the present study was to compare the effects of applying joint mobilization at symptomatic and asymptomatic cervical levels in patients with chronic nonspecific neck pain. Forty-eight patients aged between 18 and 65 years and presenting nonspecific neck pain with a minimum duration of 3 months were recruited for the study. Included patients were randomized to one of two treatment groups: (i) control group: the most symptomatic vertebral level was mobilized; (ii) experimental group: a randomly selected vertebral level was chosen and mobilized. All patients received one treatment session. Pain intensity in resting position during the most painful active cervical movement as well as during vertebral palpation was quantified using an 11-point pain scale. Follow-up measures were taken immediately after intervention by a blinded assessor. The results showed no significant difference in pain intensity immediately after treatment between groups (symptomatic level treated vs. randomly chosen cervical vertebral level treated) during resting position, painful active movement, or vertebral palpation. Within-group comparisons showed significant pain relief after treatment during the most painful active movement as well as during vertebral palpation for both groups, but not during resting position. Significant change in immediate pain intensity during painful active movement and vertebral palpation was achieved after vertebral mobilization. however, both groups presented similar pain reductions suggesting that pain reduction due to joint mobilization is not specific to the vertebral level being mobilized.
PMCID: PMC2700500  PMID: 20046551
Manual Therapy; Mobilization; Neck Pain; Randomized Clinical Trial
21.  An activating β1 integrin mutation increases conversion of benign to malignant skin tumours 
Cancer research  2009;69(4):1334-1342.
A major challenge is to identify the physiological relevance of cancer-associated genetic polymorphisms. Several changes in the coding sequence of β integrin subunits have now been described in human tumours. One of these, T188Iβ1, was identified as a heterozygous mutation in a poorly differentiated squamous cell carcinoma (SCC) and shown to activate extracellular matrix adhesion and inhibit keratinocyte differentiation in vitro. To study its contribution to tumour development, we overexpressed the mutant or wild-type (WT) human β1 subunit in the basal layer of mouse epidermis using the keratin 14 promoter. The transgenic integrins were expressed at the cell surface and were functional, T188Iβ1 promoting cell spreading to a greater extent than WTβ1. Epidermal proliferation and differentiation were unaffected and no expansion of the stem cell compartment was detected. During chemical carcinogenesis both transgenes increased papilloma formation, but only the T188Iβ1 transgene stimulated conversion of papillomas to SCCs. Papillomas bearing the mutation showed increased Erk activity and reduced differentiation. SCCs expressing T188Iβ1 were less well differentiated than those expressing WTβ1. These observations establish that expression of a genetic variant in the I-like domain of β1 integrins does not affect normal epidermal homeostasis, but increases tumour susceptibility and influences tumour type.
PMCID: PMC2644725  PMID: 19190332
22.  Responsiveness of the Brazilian–Portuguese version of the Oswestry Disability Index in subjects with low back pain 
European Spine Journal  2008;17(8):1101-1106.
When quality of life questionnaires are used as measures of treatment outcomes, it is essential to know how well these can respond to clinical changes. The objective of this study is to examine the responsiveness of the Brazilian–Portuguese version of the Oswestry Disability Index (ODI-Brazil) in subjects with chronic low back pain submitted to a physical therapy program. Thirty subjects with chronic low back pain completed the ODI-Brazil questionnaire, along with an 11-point pain visual analogue scale (Pain VAS), and the Brazilian–Portuguese version of Roland–Morris disability questionnaire before and after the program. All patients also completed a global perception of change Likert scale in condition after the program. This scale was collapsed to produce a dichotomous variable outcome: improved and non-improved. Responsiveness was determined using effect size statistics and receiver operating characteristic curve (ROC curve), with best cut-point analysis. The best change score cut-off was identified when equally balanced sensitivity and specificity was found, as an expression of the minimum clinically important difference (MCID). After treatment, 19 patients considered themselves improved. Both the effect size (0.37) and the area under the ROC curve (0.73) for ODI-Brazil score in relation to global outcome after program indicated that the ODI-Brazil showed responsiveness. The ROC curve for ODI-Brazil was distributed at the upper corners of the diagonal line, indicating that the questionnaire presents discriminative ability. The best cut-off point for ODI-Brazil was approximately 4.45 points (63.2% sensitivity, 81.8% specificity). The Brazilian–Portuguese version of ODI has comparable responsiveness to other commonly used functional status measures and is appropriate for use in chronic low back pain patients receiving conservative care.
PMCID: PMC2518761  PMID: 18512083
Low back pain; Disability; Oswestry Disability Index; Responsiveness
23.  A randomized controlled trial of tai chi for long-term low back pain (TAI CHI): Study rationale, design, and methods 
Low back pain persisting for longer than 3 months is a common and costly condition for which many current treatments have low-moderate success rates at best. Exercise is among the more successful treatments for this condition, however, the type and dosage of exercise that elicits the best results is not clearly defined. Tai chi is a gentle form of low intensity exercise that uses controlled movements in combination with relaxation techniques and is currently used as a safe form of exercise for people suffering from other chronic pain conditions such as arthritis. To date, there has been no scientific evaluation of tai chi as an intervention for people with back pain. Thus the aim of this study will be to examine the effects of a tai chi exercise program on pain and disability in people with long-term low back pain.
Methods and design
The study will recruit 160 healthy individuals from the community setting to be randomised to either a tai chi intervention group or a wait-list control group. Individuals in the tai chi group will attend 2 tai chi sessions (40 minutes)/week for 8 weeks followed by 1 tai chi session/week for 2 weeks. The wait-list control will continue their usual health care practices and have the opportunity to participate in the tai chi program once they have completed the follow-up assessments. The primary outcome will be bothersomeness of back symptoms measured with a 0–10 numerical rating scale. Secondary outcomes include, self-reports of pain-related disability, health-related quality of life and global perceived effect of treatment. Statistical analysis of primary and secondary outcomes will be based on the intention to treat principle. Linear mixed models will be used to test for the effect of treatment on outcome at 10 weeks follow up. This trial has received ethics approval from The University of Sydney Human Research Ethics Committee. HREC Approval No.10452
This study will be the first trial in this area and the information on its effectiveness will allow patients, clinicians and treatment funders to make informed choices regarding this treatment.
Trial Registration
This trial has been registered with Australian New Zealand Clinical Trials Registry. ACTRN12608000270314
PMCID: PMC2702312  PMID: 19473546
24.  Ultrasonographic Measurement of Neck Muscle Recruitment: A Preliminary Investigation 
Chronic cervical pain is a common source of disability in society, and evidence suggests that individuals with neck pain have impairment of the deep cervical flexor (DCF) muscles. This study investigated the recruitment pattern of the neck muscles, particularly the DCF, during the Craniocervical Flexion Test (CCFT), using ultrasound measurement of muscle activity in asymptomatic subjects. In a cross-sectional design, 10 subjects, of both sexes, with no history of neck pain participated in the study. Participants were instructed to perform the CCFT, and changes in thickness from resting baseline values during the five incremental stages of the test were obtained for DCF and sternocleidomastoid (SCM) muscles using ultrasonography. The most significant changes found in DCF thickness were between phase 1 and phases 4 (p<0.001) and 5 (p= <0.001). For SCM, differences were most significant between phases 1 and 3 (p<0.001), 4 (p<0.001), and 5 (p<0.001); and between phases 3 and 5 (p<0.003). No differences were found between DCF and SCM muscles. The present study confirms the evidence that CCFT increases DCF recruitment. However, the ultrasonography test protocol did not identify differences in recruitment between deep and superficial neck muscles. The present study confirms the evidence that the CCFT challenges the cervical spine and that DCF activity is increased during this maneuver.
PMCID: PMC2565110  PMID: 19119393
Craniocervical Flextion Test; Motor Control; Neck Muscles; Ultrasonography
25.  Drugs for relief of pain in patients with sciatica: systematic review and meta-analysis 
Objective To investigate the efficacy and tolerability of analgesic and adjuvant pain drugs typically administered in primary care for the management of patients with sciatica.
Design Systematic review.
Data source International Pharmaceutical Abstracts, PsycINFO, Medline, Embase, Cochrane Central Register of Clinical Trials (CENTRAL), CINAHL, and LILACS.
Study selection Randomised controlled trials assessing the efficacy and tolerability of drugs versus placebo or other treatment for sciatica.
Data extraction Two independent reviewers extracted data and assessed methodological quality using the PEDro scale. Pain and disability outcomes were converted to a common 0 to 100 scale. Data were pooled with a random effects model, and the GRADE approach was used in summary conclusions.
Results Twenty three published reports met the inclusion criteria. The evidence to judge the efficacy of non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, antidepressants, anticonvulsants, muscle relaxants, and opioid analgesics ranged from moderate to low quality. Most of the pooled estimates did not favour the active treatment over placebo. The pooled results of two trials of corticosteroids (mean difference in overall and leg pain −12.2, 95% confidence interval −20.9 to −3.4) and a single trial of the anticonvulsant gabapentin for chronic sciatica (mean difference in overall pain relief −26.6, −38.3 to −14.9) showed some benefits but only in the short term. The median rate of adverse events was 17% (interquartile range 10-30%) for the active drugs and 11% (3-23%) for placebo. Trial limitations included failure to use validated outcome measures, lack of long term follow-up, and small sample size.
Conclusions As the existing evidence from clinical trials is of low quality, the efficacy and tolerability of drugs commonly prescribed for the management of sciatica in primary care is unclear.
PMCID: PMC3278391  PMID: 22331277

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