CHARIOT: a phase I study of berzosertib with chemoradiotherapy in oesophageal and other solid cancers using time to event continual reassessment method.

BACKGROUND: Berzosertib (M6620) is a highly potent (IC50 = 19 nM) and selective, first-in-class ataxia telangiectasia-mutated and Rad3-related protein kinase (ATR) inhibitor. This trial assessed the safety, preliminary efficacy, and tolerance of berzosertib in oesophageal cancer (A1 cohort) with RT and advanced solid tumours (A2 cohort) with cisplatin and capecitabine. METHODS: Single-arm, open-label dose-escalation (Time-to-Event Continual Reassessment Method) trial with 16 patients in A1 and 18 in A2. A1 tested six dose levels of berzosertib with RT (35 Gy over 15 fractions in 3 weeks). RESULTS: No dose-limiting toxicities (DLTs) in A1. Eight grade 3 treatment-related AEs occurred in five patients, with rash being the most common. The highest dose (240 mg/m2) was determined as the recommended phase II dose (RP2D) for A1. Seven DLTs in two patients in A2. The RP2D of berzosertib was 140 mg/m2 once weekly. The most common grade ≥3 treatment-related AEs were neutropenia and thrombocytopenia. No treatment-related deaths were reported. CONCLUSIONS: Berzosertib combined with RT is feasible and well tolerated in oesophageal cancer patients at high palliative doses. Berzosertib with cisplatin and capecitabine was well tolerated in advanced cancer. Further investigation is warranted in a phase 2 setting. CLINICAL TRIALS IDENTIFIER: EU Clinical Trials Register (EudraCT) - 2015-003965-27 ClinicalTrials.gov - NCT03641547.

Occupational Fall Risk Assessment Tool for older workers.

BACKGROUND: No easy-to-use fall risk assessment tools have been devised to assess occupational fall risk in older workers. AIMS: To develop an Occupational Fall Risk Assessment Tool (OFRAT) and report its predictive validity and reliability in older workers. METHODS: The baseline fall risk assessment was completed by 1113 participants aged ≥60 years who worked ≥4 days/month in Saitama, Japan. Participants were followed up for falls during occupational activities for 1 year, and 30 participants were assessed twice for test-retest reliability. The following assessment measures were summed to form the OFRAT risk score: older age, male sex, history of falls, physical work participation, diabetes, use of medications increasing fall risk, reduced vision, poor hearing, executive dysfunction and slow stepping. The scores were then classified into four grades (0-2 points: very low, 3 points: low, 4 points: moderate and ≥5 points: high). RESULTS: During follow-up, 112 participants fell 214 times during work. The negative binomial regression model showed that participants with higher grades had a higher incidence rate ratio [95% confidence interval] for falls than those with very low grades (low: 1.64 [1.08-2.47], moderate: 4.23 [2.82-6.34] and high: 6.12 [3.83-9.76]). The intraclass correlation coefficient for risk score was 0.86 [0.72-0.93], and the weighted kappa coefficient for grade assessment was 0.74 [0.52-0.95]. CONCLUSIONS: The OFRAT is a valid and reliable tool for estimating the occupational fall risk in older workers. It may assist occupational physicians implement strategies to prevent falls in this group.

Radiogenomic analysis of primary breast cancer reveals [18F]-fluorodeoxglucose dynamic flux-constants are positively associated with immune pathways and outperform static uptake measures in associating with glucose metabolism.

BACKGROUND: PET imaging of 18F-fluorodeoxygucose (FDG) is used widely for tumour staging and assessment of treatment response, but the biology associated with FDG uptake is still not fully elucidated. We therefore carried out gene set enrichment analyses (GSEA) of RNA sequencing data to find KEGG pathways associated with FDG uptake in primary breast cancers. METHODS: Pre-treatment data were analysed from a window-of-opportunity study in which 30 patients underwent static and dynamic FDG-PET and tumour biopsy. Kinetic models were fitted to dynamic images, and GSEA was performed for enrichment scores reflecting Pearson and Spearman coefficients of correlations between gene expression and imaging. RESULTS: A total of 38 pathways were associated with kinetic model flux-constants or static measures of FDG uptake, all positively. The associated pathways included glycolysis/gluconeogenesis ('GLYC-GLUC') which mediates FDG uptake and was associated with model flux-constants but not with static uptake measures, and 28 pathways related to immune-response or inflammation. More pathways, 32, were associated with the flux-constant K of the simple Patlak model than with any other imaging index. Numbers of pathways categorised as being associated with individual micro-parameters of the kinetic models were substantially fewer than numbers associated with flux-constants, and lay around levels expected by chance. CONCLUSIONS: In pre-treatment images GLYC-GLUC was associated with FDG kinetic flux-constants including Patlak K, but not with static uptake measures. Immune-related pathways were associated with flux-constants and static uptake. Patlak K was associated with more pathways than were the flux-constants of more complex kinetic models. On the basis of these results Patlak analysis of dynamic FDG-PET scans is advantageous, compared to other kinetic analyses or static imaging, in studies seeking to infer tumour-to-tumour differences in biology from differences in imaging. Trial registration NCT01266486, December 24th 2010.

Characterising 18F-fluciclovine uptake in breast cancer through the use of dynamic PET/CT imaging.

BACKGROUND: 18F-fluciclovine is a synthetic amino acid positron emission tomography (PET) radiotracer that is approved for use in prostate cancer. In this clinical study, we characterised the kinetic model best describing the uptake of 18F-fluciclovine in breast cancer and assessed differences in tracer kinetics and static parameters for different breast cancer receptor subtypes and tumour grades. METHODS: Thirty-nine patients with pathologically proven breast cancer underwent 20-min dynamic PET/computed tomography imaging following the administration of 18F-fluciclovine. Uptake into primary breast tumours was evaluated using one- and two-tissue reversible compartmental kinetic models and static parameters. RESULTS: A reversible one-tissue compartment model was shown to best describe tracer uptake in breast cancer. No significant differences were seen in kinetic or static parameters for different tumour receptor subtypes or grades. Kinetic and static parameters showed a good correlation. CONCLUSIONS: 18F-fluciclovine has potential in the imaging of primary breast cancer, but kinetic analysis may not have additional value over static measures of tracer uptake. CLINICAL TRIAL REGISTRATION: NCT03036943.

Visuospatial working memory and obstacle crossing in young and older people.

Obstacle crossing requires visuospatial working memory to guide the trailing leg trajectory when vision in unavailable. Visuospatial working memory, as assessed with neuropsychological tests, declines with age, however, this remains to be investigated functionally in obstacle crossing. There is also evidence that visuospatial encoding during a secondary task interferes with balance control during stepping and walking in older people. Here, we studied the interaction effects of age by delay (study 1) and age by secondary visuospatial task (study 2) conditions on obstacle clearance in a visuospatial working memory -guided obstacle crossing task. Healthy young adults aged 19 to 36 years (n = 20 in study 1 and n = 17 in study 2) and healthy older adults aged 66 to 83 years (n = 29 in study 1 and n = 21 in study 2) were instructed to step over an obstacle with their leading leg and straddle it for a delay period before completing the crossing with their trailing leg. In study 1, two obstacle height conditions (12 cm, 18 cm) and two delay durations (20 s, 60 s) were presented in random order. In study 2, participants were required to attend to either no secondary task (control), a visuospatial secondary (star movement) task, or a nonspatial secondary (arithmetic) task, while straddling the obstacle for a delay duration of 20 s, at obstacle heights of 12 cm and 18 cm, randomly presented. Trailing leg kinematics (mean and variability of maximum toe clearance over the obstacle) were determined via motion capture. There were no statistically significant age by delay or age by secondary task interactions. In study 1, toe clearance variability was significantly greater in young adults and increased with increasing delay duration in both groups. In study 2, compared with the control condition, toe clearance variability was significantly greater in the non-spatial secondary task condition but not in the visuospatial condition. Contrary to our hypotheses, these findings suggest that young and older adults alike can store an obstacle representation via visuospatial working memory for durations of at least 60 s and use this information to safely scale their trailing leg over an obstacle. However, the increase in trailing leg toe clearance variability with delay duration suggests that obstacle representation starts to deteriorate even within the first 20 s regardless of age. The finding that undertaking a concurrent arithmetic task impaired visuospatial working memory-guided obstacle clearance suggests a potential increased risk of tripping during obstacle crossing while dual-tasking in both young and older people.

Phonological complexity in intervention for Spanish-speaking children with speech sound disorder.

The efficiency of intervention for children with speech sound disorder may be influenced by linguistic complexity of the phonological intervention target. Complex targets, particularly, later-acquired, less-known consonants and consonant clusters, have been linked to greater post-intervention generalization to untargeted phonological structures. Yet there is little direct evidence to support target selection based on linguistic complexity for Spanish-speaking children with speech sound disorder. This intervention study utilizes an experimental single-case design to examine the efficacy of intervention in Spanish using different complex targets (i.e. /ɡɾ/, /bɾ/, and /l/). For each of the four Spanish-speaking children with speech sound disorder, sounds at 0% accuracy during baseline were monitored across the baseline period, during and post-intervention, and at one- and two-month follow-up visits. Over the course of intervention, only one participant achieved mastery of the targeted structure in practiced words. However, all participants demonstrated some amount of broad phonological generalization to untargeted consonants or clusters. Variable learning trajectories and broad phonological generalization are discussed as they relate to participant characteristics and linguistic complexity.

Prevalence of motor impairment in residents of New South Wales, Australia aged 55 years and over: cross-sectional survey of the 45 and Up cohort.

BACKGROUND: The population prevalence of many diseases is known. However, little is known of the population prevalence of motor impairments. METHODS: The aim of this study was to determine the point prevalence of specific motor impairments (weakness, fatigue, contracture, impaired balance and impaired coordination) in the population aged 55 years and older resident in New South Wales, Australia in 2018. 55,210 members of the 45 and Up cohort were invited to participate in a follow-up survey that included questions on motor impairment. Responses were received from 20,141 people (36%). Calibrated estimates of prevalence of specific motor impairments, and of having at least one motor impairment, were obtained using survey weights based on the known multivariate distributions of age, gender and geographical location (28 regions) in the population. RESULTS: More than one-third of adults aged over 55 residing in New South Wales have difficulty using their hands, arms or legs. The prevalence of each motor impairment (muscle weakness, fatigue, contracture, impaired balance or impaired coordination) in this population is between 4 and 12%. The prevalence of at least one of these impairments is 21%. The prevalence of at least one impairment in people aged 85 and over is 42%. Women consistently had more difficulty using hands, arms and legs, and more motor impairment, than men. Difficulty using hands, arms and legs and the prevalence of all motor impairments, especially poor balance, greatly increased with age. CONCLUSION: The prevalence of specific motor impairments in older Australian adults is high - comparable to that of the most prevalent diseases. There may be merit in considering motor impairment as a significant public health problem in its own right.

Risk factors for falls in patients with total hip arthroplasty and total knee arthroplasty: a systematic review and meta-analysis.

OBJECTIVE: Falls are common after total hip arthroplasty (THA) and total knee arthroplasty (TKA). While previous studies have investigated various risk factors for falls in patients following THA and TKA, no systematic reviews have summarized these risk factors. Therefore, the current systematic review aimed to summarize evidence regarding risk factors for falls in patients after THA and/or TKA. METHODS: MEDLINE, EMBASE, CINAHL, SPORTDiscus, and Physiotherapy Evidence Database (from inception to June 30, 2018) were searched. The methodological quality and quality of evidence of the included studies were assessed by two independent reviewers. Relevant data regarding participants' characteristics, study design, follow-up time points, and identified risk factors were extracted. Meta-analyses and narrative syntheses were performed. RESULTS: Twelve studies with a total of 1,292,689 participants were included. Twenty-nine identified risk factors for post-THA/TKA falls were classified into either inpatient or post-discharge risk factors. Key risk factors for both post-THA and/or post-TKA inpatient falls that showed moderate level of evidence included: postoperative complications or comorbidities and revision THA/TKA. Likewise, risk factors for post-discharge falls after THA and/or TKA that demonstrated moderate level of evidence included: medications, psychiatric diseases, living alone, prior history of TKA, falls history and female gender. The quality of the included studies varied and sample sizes were not justified. CONCLUSIONS: This review summarized both non-modifiable and modifiable risk factors for post-THA/TKA falls. Our findings highlight the importance of developing strategies to lower the falls risk among patients following THA/TKA.

A randomised phase II trial and feasibility study of palliative chemotherapy in frail or elderly patients with advanced gastroesophageal cancer (321GO).

BACKGROUND: Elderly patients are commonly under-represented in cancer clinical trials. The 321GO was undertaken in preparation for a definitive phase three trial assessing different chemotherapy regimens in a frail and/or elderly population with advanced gastroesophageal (GO) cancer. METHODS: Patients with advanced GO cancer considered unfit for conventional dose chemotherapy were randomly assigned in a 1 : 1 : 1 ratio to: epirubicin, oxaliplatin and capecitabine (EOX); oxaliplatin and capecitabine (OX); and capecitabine alone (X) (all 80% of full dose and unblinded). The primary end point was patient recruitment over an 18-month period. A registration study recorded treatment choice for all patients with advanced GO cancer at trial centres. RESULTS: A total of 313 patients were considered for palliative chemotherapy for GO cancer over the 18-month period: 115 received full dose treatment, 89 less than standard treatment or entered 321GO and 111 no treatment. Within 321GO, 55 patients were randomly assigned (19 to OX and X; 17 to EOX). Progression-free survival (PFS) for all patients was 4.4 months and by arm 5.4, 5.6 and 3.0 months for EOX, OX and X, respectively. The number of patients with a good overall treatment utility (OTU), a novel patient-centred endpoint, at 12 weeks was 3 (18%), 6 (32%) and 1 (6%) for EOX, OX and X, respectively. At 6 weeks, 22 patients (41%) had experienced a non-haematologic toxicity ⩾grade 3, most commonly lethargy or diarrhoea. The OTU was prognostic for overall survival in patients alive at week 12 (logrank test P=0.0001). CONCLUSIONS: It is feasible to recruit elderly and/or frail patients with advanced GO cancer to a randomised clinical trial. The OX is the preferred regimen for further study. Overall treatment utility shows promise as a comparator between treatment regimens for feasibility and randomised trials in the elderly and/or frail GO cancer population.

Strength measures are better than muscle mass measures in predicting health-related outcomes in older people: time to abandon the term sarcopenia?

There is no clear consensus on definition, cut-points or standardised assessments of sarcopenia. We found a lower limb strength assessment was at least as effective in predicting balance, mobility and falls in 419 older people as muscle mass-based measures of sarcopenia. INTRODUCTION: There is currently no consensus on the definition, cut-points or standardised assessments of sarcopenia. This study aimed to investigate whether several published definitions of sarcopenia differentiate between older people with respect to important functional and health outcomes. METHODS: Four hundred nineteen community-living older adults (mean age 81.2 ± 4.5, 49 % female) completed assessments of body composition (dual-energy X-ray absorptiometry), strength, balance, mobility and disability. Falls were recorded prospectively for a year using monthly calendars. Sarcopenia was defined according to four skeletal mass-based definitions, two strength-based definitions (handgrip or knee extensor force) and a consensus algorithm (low mass and low strength or slow gait speed). Obesity was defined according to percentage fat mass or waist circumference. RESULTS: The four skeletal mass-based definitions varied considerably with respect to the percentage of participants classified as sarcopenic and their predictive accuracy for functional and health outcomes. The knee extension strength-based definition was equivalent to or better than the mass-based and consensus algorithm definitions; i.e. weaker participants performed poorly in tests of leaning balance, stepping reaction time, gait speed and mobility. They also had higher physiological fall risk scores and were 43 % more likely to fall at home than their stronger counterparts. Adding obesity to sarcopenia definitions identified participants with greater self-reported disability. CONCLUSIONS: A simple lower limb strength assessment was at least as effective in predicting balance, functional mobility and falls in older people as more expensive and time-consuming muscle mass-based measures. These findings imply that functional terms such as muscle weakness or motor impairment are preferable to sarcopenia.

Fall-related hospitalization in people with Parkinson's disease.

BACKGROUND AND PURPOSE: Falls are common in people with Parkinson's disease (PD) but few data exist on fall-related hospitalizations in this group. This population-based study compared fall-related hospital admissions, injury rates and consequences in people with and without PD, and determined whether PD was an independent predictor of fall-related hospital length of stay. METHODS: This was a retrospective study using probabilistic linkage of hospital data in people aged ≥65 years hospitalized for a fall between 1 July 2005 and 31 December 2013 in New South Wales, Australia. Rates of hospital admissions and injuries per person admitted over the study period were compared between people with and without PD using Poisson or negative binomial regression. Multilevel linear modelling was used to analyse length of stay by clustering individuals and adjusting for possible confounders. RESULTS: There were 342 265 fall-related hospital admissions in people aged ≥65 years during the study period, of which 8487 (2.5%) were for people with PD. Sixty-seven per cent of fall-related PD admissions were associated with injury and 35% were associated with fracture. People with PD had higher rate ratios for fall admissions (1.63, 95% confidence interval 1.59-1.67) and injury (1.47, 95% confidence interval 1.43-1.51) and longer median length of stay [9 (interquartile range 1-27) vs. 6 (interquartile range 1-20) days in people without PD; P < 0.001]. PD remained associated with increased length of stay after controlling for comorbidity, age, sex and injury (P < 0.001). CONCLUSIONS: This study provides important benchmark data for hospitalizations for falls and fall injuries for older people with PD, which may be used to monitor the effect of fall prevention programmes.

Use of a physiological profile to document motor impairment in ageing and in clinical groups.

Ageing decreases exercise performance and is frequently accompanied by reductions in cognitive performance. Deterioration in the physiological capacity to stand, locomote and exercise can manifest itself as falling over and represents a significant deterioration in sensorimotor control. In the elderly, falling leads to serious morbidity and mortality with major societal costs. Measurement of a suite of physiological capacities that are required for successful motor performance (including vision, muscle strength, proprioception and balance) has been used to produce a physiological profile assessment (PPA) which has been tracked over the age spectrum and in different diseases (e.g. multiple sclerosis, Parkinson's disease). As well as measures of specific physiological capacities, the PPA generates an overall 'score' which quantitatively measures an individual's cumulative risk of falling. The present review collates data from the PPA (and the physiological capacities it measures) as well as its use in strategies to reduce falls in the elderly and those with different diseases. We emphasise that (i) motor impairment arises via reductions in a wide range of sensorimotor abilities; (ii) the PPA approach not only gives a snapshot of the physiological capacity of an individual, but it also gives insight into the deficits among groups of individuals with particular diseases; and (iii) deficits in seemingly restricted and disparate physiological domains (e.g. vision, strength, cognition) are funnelled into impairments in tasks requiring upright balance. Motor impairments become more prevalent with ageing but careful physiological measurement and appropriate interventions offer a way to maximise health across the lifespan.

The performance of risk prediction models for pre-eclampsia using routinely collected maternal characteristics and comparison with models that include specialised tests and with clinical guideline decision rules: a systematic review.

BACKGROUND: Risk prediction models may be valuable to identify women at risk of pre-eclampsia to guide aspirin prophylaxis in early pregnancy. OBJECTIVE: To assess the performance of 'simple' risk models for pre-eclampsia that use routinely collected maternal characteristics; compare with 'specialised' models that include specialised tests; and to guideline recommended decision rules. SEARCH STRATEGY: MEDLINE, Embase and PubMed were searched to June 2014. SELECTION CRITERIA: We included studies that developed or validated pre-eclampsia risk models using maternal characteristics with or without specialised tests and reported model performance. DATA COLLECTION AND ANALYSIS: We extracted data on study characteristics; model predictors, validation and performance including area under the curve (AUC), sensitivity and specificity. MAIN RESULTS: We identified 29 studies that developed 70 models including 22 simple models. Studies included 151-9149 women with a pre-eclampsia prevalence of 1.2-9.5%. No single predictor was included in all models. Four simple models were externally validated, with a model using parity, pre-eclampsia history, race, chronic hypertension and conception method to predict early-onset pre-eclampsia achieving the highest AUC (0.76, 95% CI 0.74-0.77). Nine studies comparing simple versus specialized models in the same population reported AUC favouring specialised models. A simple model achieved fewer false positives than a guideline recommended risk factor list, but sensitivity to classify risk for aspirin prophylaxis was not assessed. CONCLUSION: Validated simple pre-eclampsia risk models demonstrate good risk discrimination that can be improved with specialised tests. Further research is needed to determine their clinical value to guide aspirin prophylaxis compared with decision rules. TWEETABLE ABSTRACT: Pre-eclampsia risk models using maternal factors show good risk discrimination to guide aspirin prophylaxis.

Health and social support services in older adults recently discharged from hospital: service utilisation and costs and exploration of the impact of a home-exercise intervention.

BACKGROUND: Admission to hospital can lead to persistent deterioration in physical functioning, particularly for the more vulnerable older population. As a result of this physical deterioration, older people who have been recently discharged from hospital may be particularly high users of health and social support services. Quantify usage and costs of services in older adults after hospitalisation and explore the impact of a home-exercise intervention on service usage. METHOD: The present study was a secondary analysis of data from a randomised controlled trial (ACTRN12607000563460). The trial involved 340 participants aged 60 years and over with recent hospitalisation. Service use and costs were compared between intervention (12 months of home-exercise prescribed in 10 visits from a physiotherapist) and control groups. RESULTS: 33 % of participants were re-admitted to hospital, 100 % consulted a General Medical Practitioner and 63 % used social services. 56 % of costs were associated with hospital admission and 22 % with social services. There was reduction in General Medical Practitioner services provided in the home in the intervention group (IRR 0.23, CI 0.1 to 0.545, p < 0.01) but no significant between-group difference in service use or in costs for other service categories. CONCLUSION: There appears to be substantial hospital and social service use and costs in this population of older people. No significant impact of a home-based exercise program was evident on service use or costs. TRIAL REGISTRATION: Australian and New Zealand Clinical Trial Registry ACTRN12607000563460 >TrialSearch.

Validity and reliability of a simple 'low-tech' test for measuring choice stepping reaction time in older people.

OBJECTIVE: To establish the psychometric properties of a simple 'low-tech' choice stepping reaction time test (CSRT-M) by investigating its validity and test-retest reliability. DESIGN: Cross-sectional. SETTING: Community. SUBJECTS: A total of 169 older people from the control arm of a clinical trial and a convenience sample of 30 older people. MAIN MEASURES: Demographic, physical, cognitive and prospective falls data were collected in addition to CSRT-M. The CSRT-M time was taken as the total time to complete 20 steps onto four targets printed on a portable rubber mat. Assessment of the original electronic version (CSRT-E) and re-administration of the CSRT-M the next day was done in 30 participants. RESULTS: Multivariate regression analysis showed that the CSRT-M time was best explained by leaning balance control, quadriceps strength and cognitive functioning (R2 = 0.44). Performance on the CSRT-M was worse in older participants and participants with a presence of fall risk factors, supporting good discriminant validity. The odds of suffering multiple future falls increased by 74% (odds ratio (OR) = 1.74, 95% CI (confidence interval) = 1.14-2.65, p = 0.010) for each standard deviation increase in CSRT-M, supporting good predictive validity. Criterion validity was confirmed by a strong bivariate correlation between CSRT-M and CSRT-E (0.81, p < 0.001). Test-retest reliability for the CSRT-M was good (intraclass correlation coefficient = 0.74, 95% CI = 0.45-0.88, p < 0.001). CONCLUSIONS: A simple test of unplanned volitional stepping (CSRT-M) has excellent predictive validity for future falls, good inter-day test-retest reliability and excellent criterion validity with respect to the well-validated CSRT-E. The CSRT-M, therefore, may be a useful fall risk screening tool for older people.

Imaging tumour hypoxia with positron emission tomography.

Hypoxia, a hallmark of most solid tumours, is a negative prognostic factor due to its association with an aggressive tumour phenotype and therapeutic resistance. Given its prominent role in oncology, accurate detection of hypoxia is important, as it impacts on prognosis and could influence treatment planning. A variety of approaches have been explored over the years for detecting and monitoring changes in hypoxia in tumours, including biological markers and noninvasive imaging techniques. Positron emission tomography (PET) is the preferred method for imaging tumour hypoxia due to its high specificity and sensitivity to probe physiological processes in vivo, as well as the ability to provide information about intracellular oxygenation levels. This review provides an overview of imaging hypoxia with PET, with an emphasis on the advantages and limitations of the currently available hypoxia radiotracers.

MIC-1/GDF15 in Barrett's oesophagus and oesophageal adenocarcinoma.

BACKGROUND: Biomarkers are needed to improve current diagnosis and surveillance strategies for patients with Barrett's oesophagus (BO) and oesophageal adenocarcinoma (OAC). Macrophage inhibitory cytokine 1/growth differentiation factor 15 (MIC-1/GDF15) tissue and plasma levels have been shown to predict disease progression in other cancer types and was therefore evaluated in BO/OAC. METHODS: One hundred thirty-eight patients were studied: 45 normal oesophagus (NE), 37 BO, 16 BO with low-grade dysplasia (LGD) and 40 OAC. RESULTS: Median tissue expression of MIC-1/GDF15 mRNA was ⩾25-fold higher in BO and LGD compared to NE (P<0.001); two-fold higher in OAC vs BO (P=0.039); and 47-fold higher in OAC vs NE (P<0.001). Relative MIC-1/GDF15 tissue expression >720 discriminated between the presence of either OAC or LGD vs NE with 94% sensitivity and 71% specificity (ROC AUC 0.86, 95% CI 0.73-0.96; P<0.001). Macrophage inhibitory cytokine 1/growth differentiation factor 15 plasma values were also elevated in patients with OAC vs NE (P<0.001) or BO (P=0.015).High MIC-1/GDF15 plasma levels (⩾1140 pg ml(-1)) were an independent predictor of poor survival for patients with OAC (HR 3.87, 95% CI 1.01-14.75; P=0.047). CONCLUSIONS: Plasma and tissue levels of MIC-1/GDF15 are significantly elevated in patients with BO, LGD and OAC. Plasma MIC-1/GDF15 may have value in diagnosis and monitoring of Barrett's disease.

Falls in people with MS--an individual data meta-analysis from studies from Australia, Sweden, United Kingdom and the United States.

BACKGROUND: Falls are common in people with multiple sclerosis (PwMS). Previous studies have generally included small samples and had varied methods. OBJECTIVES: The objectives of this paper are to compile fall rates across a broad range of ages and disease severity and to definitively assess the extent to which MS-associated and demographic factors influence fall rates. METHODS: Individual data from studies in four countries that prospectively measured falls for three months were analyzed. We determined fall rates, prevalence of fallers (≥1 falls) and frequent fallers (≥2 falls), location and timing of falls, and fall-related demographic factors. RESULTS: A total of 537 participants reported 1721 falls: 56% were fallers and 37% frequent fallers. Most falls occurred indoors (65%) between 6 a.m. and 6 p.m. (75%). Primary progressive MS was associated with significantly increased odds of being a faller (odds ratio (OR) 2.02; CI 1.08-3.78). Fall risk peaked at EDSS levels of 4.0 and 6.0 with significant ORs between 5.30 (2.23-12.64) and 5.10 (2.08-12.47). The fall rate was lower in women than men (relative risk (RR) 0.80; CI 0.67-0.94) and decreased with increasing age (RR 0.97 for each year, CI 0.95-0.98). CONCLUSION: PwMS are at high risk of falls and there are important associations between falls and MS-associated disability, gender and age.

The effect of a workplace intervention programme on return to work after stroke: a randomised controlled trial.

OBJECTIVE: To determine the effect of a workplace intervention programme on the rate of return to work of previously employed stroke survivors in the Gauteng province of South Africa. DESIGN: A randomised controlled trial. SETTING: Participants' workplaces and three hospitals with stroke rehabilitation facilities. SUBJECTS: Eighty stroke survivors between the ages of 18 and 60 years who were employed at the time of stroke onset. INTERVENTION: The workplace intervention programme was tailored according to functional ability and workplace challenges of each stroke survivor. The control group received usual stroke care which took into consideration job requirements but without workplace intervention. MAIN OUTCOMES: The primary outcome was return to work rate. Secondary outcomes included activities of daily living (ADLs), mobility, basic cognitive function and perceived quality of life. RESULTS: At six months follow-up 60% (n = 24) of stroke survivors in the intervention group returned to work compared to 20% (n = 8) in the control group (P <0.001). The odds ratio for return to work for stroke survivors in the intervention group was 5.2. For every unit increase in the ADLs and cognitive assessment score, the odds of return to work increased by 1.7 and 1.3 respectively; those who returned to work had better quality of life than those who did not return to work (P = 0.05). CONCLUSION: A workplace intervention consisting of workability assessments and workplace visits was effective in facilitating return to work for stroke survivors in the Gauteng province of South Africa.

Walleye Sander vitreus (Mitchill) are relatively resistant to experimental infection with VHSV IVb and extant walleye strains vary in susceptibility.

Compared to fathead minnow, walleye demonstrate low susceptibility to experimental infection with VHSV IVb, regardless of route of exposure or water temperature at time of infection. In triplicate and duplicate groups, walleye were intraperitoneally (i.p.) injected (102 -108  pfu/fish) or waterborne-exposed (w; 1.4 × 107  pfu mL-1 ) with VHSV IVb. High cumulative mortality (64-100%) and severe gross lesions associated with VHSV IVb infection were evident only in fish i.p. injected with 108  pfu at 12 °C. These fish had multifocal necrosis of several tissues including the gill and heart. There was no difference in mortality between walleye infected (w or i.p.) at 12 °C (spring stocking) compared with a declining temperature profile from 18 to 12 °C (fall stocking). There were significant differences (P < 0.05) in mortality between four extant walleye strains following i.p. infection, indicating that the choice of walleye strain for stocking might be an important consideration. Viral antigen was found in both i.p. and w-exposed walleye using immunohistochemistry, mostly within the gill and skin of w-exposed fish and most prominently in dermal fibrocytes. VHSV IVb was detected in multiple tissues from 6 to 21 days post-infection using reverse transcriptase quantitative polymerase chain reaction (RT-qPCR).