The role of Cathepsin S as a marker of prognosis and predictor of chemotherapy benefit in adjuvant CRC: a pilot study.

BACKGROUND: The aim of this pilot retrospective study was to investigate the immunohistochemical expression of Cathepsin S (CatS) in three cohorts of colorectal cancer (CRC) patients (n=560). METHODS: Prevalence and association with histopathological variables were assessed across all cohorts. Association with clinical outcomes was investigated in the Northern Ireland Adjuvant Chemotherapy Trial cohort (n=211), where stage II/III CRC patients were randomised between surgery-alone or surgery with adjuvant fluorouracil/folinic acid (FU/FA) treatment. RESULTS: Greater than 95% of tumours had detectable CatS expression with significantly increased staining in tumours compared with matched normal colon (P>0.001). Increasing CatS was associated with reduced recurrence-free survival (RFS; P=0.03) among patients treated with surgery alone. Adjuvant FU/FA significantly improved RFS (hazard ratio (HR), 0.33; 95% CI, 0.12-0.89) and overall survival (OS; HR, 0.25; 95% CI, 0.08-0.81) among 36 patients with high CatS. Treatment did not benefit the 66 patients with low CatS, with a RFS HR of 1.34 (95% CI, 0.60-3.19) and OS HR of 1.33 (95% CI, 0.56-3.15). Interaction between CatS and treatment status was significant for RFS (P=0.02) and OS (P=0.04) in a multivariate model adjusted for known prognostic markers. CONCLUSION: These results signify that CatS may be an important prognostic biomarker and predictive of response to adjuvant FU/FA in CRC.

The effect of topical phenytoin on healing in diabetic foot ulcers: a randomized controlled trial.

AIM: The aim of the study was to evaluate the effect of topical phenytoin on healing in diabetic foot ulcers. A randomized, controlled, double-blind, clinical trial was conducted. METHODS: A phenytoin dressing and a control dressing were manufactured. Individuals who were ≥ 18 years of age with peripheral neuropathy, an ankle brachial pressure index > 0.5 and a diabetic foot ulcer ≥ 4 weeks' duration were independently randomized to the phenytoin group (31 participants) or the control group (34 participants). Participants with renal disease, ankle brachial pressure index < 0.5, necrosis or osteomyelitis were excluded. Subjects received standard wound care and dressing application. Primary endpoint analysis (diabetic foot ulcer closed or not at 16 weeks) was calculated by survival analysis. RESULTS: Participants (n = 65, 52 with Type 2 diabetes) were treated for a maximum of 16 weeks. Sixty per cent of the diabetic foot ulcers closed overall (18 in the phenytoin group, 20 in the control group) with no statistically significant differences in complete healing or in diabetic foot ulcer area over time between the two groups. At 24-weeks follow-up, one diabetic foot ulcer had recurred. CONCLUSIONS: There were no differences in diabetic foot ulcer closure rates or in diabetic foot ulcer area over time between the two groups. This study does not support the use of phenytoin in the treatment of diabetic foot ulcers.

The burden of fatal and non-fatal injury in rural India.

BACKGROUND: Little is known about the burden or causes of injury in rural villages in India. OBJECTIVE: To examine injury-related mortality and morbidity in villages in the state of Andhra Pradesh, India. METHODS: A verbal-autopsy-based mortality surveillance study was used to collect mortality data on all ages from residents in 45 villages in 2003-2004. In early 2005, a morbidity survey in adults was carried out using stratified random sampling in 20 villages. Participants were asked about injuries sustained in the preceding 12 months. Both fatal and non-fatal injuries were coded using classification methods derived from ICD-10. RESULTS: Response rates for the mortality surveillance and morbidity survey were 98% and 81%, respectively. Injury was the second leading cause of death for all ages, responsible for 13% (95% CI 11% to 15%) of all deaths. The leading causes of fatal injury were self-harm (36%), falls (20%), and road traffic crashes (13%). Non-fatal injury was reported by 6.7% of survey participants, with the leading causes of injury being falls (38%), road traffic crashes (25%), and mechanical forces (16.1%). Falls were more common in women, with most (72.3%) attributable to slipping and tripping. Road traffic injuries were sustained mainly by men and were primarily the result of motorcycle crashes (48.8%). DISCUSSION: Injury is an important contributor to disease burden in rural India. The leading causes of injury-falls, road traffic crashes, and suicides-are all preventable. It is important that effective interventions are developed and implemented to minimize the impact of injury in this region.

In vivo macular pigment measurements: a comparison of resonance Raman spectroscopy and heterochromatic flicker photometry.

AIM: To investigate whether two methods of measuring macular pigment-namely, heterochromatic flicker photometry (HFP) and resonance Raman spectroscopy (RRS)--yield comparable data. METHODS: Macular pigment was measured using HFP and RRS in the right eye of 107 participants aged 20-79 years. Correlations between methods were sought and regression models generated. RRS was recorded as Raman counts and HFP as macular pigment optical density (MPOD). The average of the top three of five Raman counts was compared with MPOD obtained at 0.5 degrees eccentricity, and an integrated measure (spatial profile; MPODsp) computed from four stimulus sizes on HFP. RESULTS: The coefficient of variation was 12.0% for MPODsp and 13.5% for Raman counts. MPODsp exhibited significant correlations with Raman counts (r = 0.260, p = 0.012), whereas MPOD at 0.5 degrees did not correlate significantly (r = 0.163, p = 0.118). MPODsp was not significantly correlated with age (p = 0.062), whereas MPOD at 0.5 degrees was positively correlated (p = 0.011). Raman counts showed a significant decrease with age (p = 0.002) and were significantly lower when pupil size was smaller (p = 0.015). CONCLUSIONS: Despite a statistically significant correlation, the correlations were weak, with those in excess of 90% of the variance between MPODsp and Raman counts remaining unexplained, meriting further research.

Incidence and risk factors for injury in non-elite netball.

This paper identifies the risk and protective factors for injury in non-elite netball. Three-hundred and sixty-eight non-elite netballers completed a baseline questionnaire at the commencement of the 1997 preseason. Participants were telephoned each month during the 1997 and 1998 playing seasons to provide details of their exposure at training and games and any injury experiences in the previous 4 weeks. The incidence of injury in this study was 14 injuries per 1000 player hours. The risk factors for injury were identified as: not warming up before a game (IRR 1.11, 95% CI 1.00-1.23) and not being open to new ideas (IRR 1.04, 95% CI 1.00-1.07). Training for 4 or more hours per week (IRR 0.66, 95% CI 0.45-0.98) and not sustaining an injury in the previous 12 months (IRR 0.58, 95% CI 0.43-0.79) were found to be protective against injury. The risk and protective factors for injury identified in this study can be used as the basis for the development of evidence-based injury prevention strategies that seek to reduce the risk of injury in sport. Injury prevention strategies should focus on the development of effective training programs that include netball-specific skills, activities and movements. Further investigation into the mechanisms associated with the risk and protective factors identified would provide further understanding of why these factors increase or decrease the risk of injury.

Further validation of the Daily Living Tasks Dependent on Vision: identification of domains.

AIM: To examine the Daily Living Tasks Dependent on Vision (DLTV), a visual function questionnaire for domain structure, and redundancy. METHOD: 235 subjects underwent full ophthalmic assessment and completed the DLTV questionnaire by interview. Principal component analysis with varimax rotation and item response theory (IRT) were used to assign the items to domains. The internal consistency of each domain was examined using Cronbach's alpha. Redundancy was assessed by regressing each item in a domain against the remainder of items in that domain. RESULTS: Four domains were identified. Domain 1 was formed by nine items, which after applying IRT were seen to be among the most difficult questions in the instrument. Domain 2 contained eight items, all of which fell in the easier half of the instrument on applying IRT. Domain 3 contained only three items, all of which were among the easier questions and appear to deal with peripheral vision function. Domain 4 consisted of two items dealing with adaptation to light and dark conditions. Cronbach's alpha for each domain was 0.96, 0.93, 0.73, 0.66. Redundancy was found to be present in domain 1, which was therefore reduced by two items, with little effect on internal consistency. CONCLUSIONS: The authors believe using the domains identified in this report will optimise the information provided by patients on their ability to function on visually demanding tasks.

Visual functioning and quality of life in the SubFoveal Radiotherapy Study (SFRADS): SFRADS report 2.

AIMS: To determine whether or not self reported visual functioning and quality of life in patients with choroidal neovascularisation caused by age related macular degeneration (AMD) is better in those treated with 12 Gy external beam radiotherapy in comparison with untreated subjects. METHODS: A multicentre single masked randomised controlled trial of 12 Gy of external beam radiation therapy (EBRT) delivered as 6 x 2 Gy fractions to the macula of an affected eye versus observation. Patients with AMD, aged 60 years or over, in three UK hospital units, who had subfoveal CNV and a visual acuity equal to or better than 6/60 (logMAR 1.0). METHODS: Data from 199 eligible participants who were randomly assigned to 12 Gy teletherapy or observation were available for analysis. Visual function assessment, ophthalmic examination, and fundus fluorescein angiography were undertaken at baseline and at 3, 6, 12, and 24 months after study entry. To assess patient centred outcomes, subjects were asked to complete the Daily Living Tasks Dependent on Vision (DLTV) and the SF-36 questionnaires at baseline, 6, 12, and 24 months after enrolment to the study. Cross sectional and longitudinal analyses were conducted using arm of study as grouping variable. Regression analysis was employed to adjust for the effect of baseline co-variates on outcome at 12 months and 24 months. RESULTS: Both control and treated subjects had significant losses in visual functioning as seen by a progressive decline in mean scores in the four dimensions of the DLTV. There were no statistically significant differences between treatment and control subjects in any of dimensions of the DLTV at 12 months or 24 months after study entry. Regression analysis confirmed that treatment status had no effect on the change in DLTV dimensional scores. CONCLUSIONS: The small benefits noted in clinical measures of vision in treated eyes did not translate into better self reported visual functioning in patients who received treatment when compared with the control arm. These findings have implications for the design of future clinical trials and studies.

Anoxia-induced changes in optimal substrate for peripheral nerve.

Hyperglycemia accentuates the injury produced by anoxia both in the central and peripheral nervous system. To understand whether this is a consequence of changes in metabolic pathways produced by anoxia, the effect of the metabolic substrate used by the rat peripheral nerve on the nerve action potential (NAP) was studied in the presence and absence of anoxia. In the continuously oxygenated state, the NAP was well preserved with glucose, lactate, as well as with high concentrations of sorbitol and fructose but not ß-hydroxybutyrate, acetate or galactose. With intermittent anoxia, the pattern of substrate effects on the NAP changed markedly so that low concentrations of fructose became able to support neurophysiologic activity but not high concentrations of glucose. These alterations occurred gradually with repeated episodes of anoxia as reflected by the progressive increase in the time needed for the NAP to disappear during anoxia when using glucose as substrate. This "preconditioning" effect was not seen with other substrates and an opposite effect was seen with lactate. In fact, the rate at which the NAP disappeared during anoxia was not simply related to degree of recovery after anoxia. These are distinct phenomena. For example, the NAP persisted longest during anoxia in the setting of hyperglycemia but this was the state in which the anoxic damage was most severe. Correlating the results with existing literature on the metabolic functions of Schwann cells and axons generates testable hypotheses for the mechanism of hyperglycemic damage during anoxia and lead to discussions of the role for a metabolic shuttle between Schwann cells and axons as well as a potential important role of glycogen.

Plasma norepinephrine and prediction of outcome in major depressive disorder.

BACKGROUND: Several epidemiologic and clinical factors have been shown to predict long term outcome in major depressive disorder (MDD). The value of biological predictors has not been extensively studied. This study examined whether plasma norepinephrine may be useful in predicting outcome in MDD. METHODS: Forty patients were followed up 8 years after an index major depressive episode. Three outcome variables were assessed: time to first recurrence (the primary outcome measure), the Lee and Murray criteria and the Depression Outcome Scale (DOS). The results were examined against plasma norepinephrine value, at the index episode, using survival analysis and linear regression. RESULTS: High plasma norepinephrine at the index episode was positively and significantly associated with time to first recurrence for patients with nonpsychotic MDD (n = 31, chi 2 = 8.38, on 1 df, p < .01). Similarly, plasma norepinephrine was significantly associated with good global outcome, both using Lee and Murray criteria (n = 34, adjusted R2 = .24, p < .01) and DOS criteria (n = 31, adjusted R2 = .17, p < .01) for this group of patients. In contrast, plasma norepinephrine was not significantly related to outcome for MDD with psychotic features. CONCLUSIONS: Plasma norepinephrine at index episode seems to be a predictor of outcome in MDD.

A case-control study of traffic risk factors and child pedestrian injury.

BACKGROUND: Pedestrian injuries in children constitute an important cause of mortality and morbidity. Specific hazards which contribute to these injuries need to be identified to enable the development of preventive strategies. METHODS: A population-based case-control study was conducted in which 40 aspects of traffic and road environment that contribute to the likelihood of childhood pedestrian injury were examined. The factors of interest were measured at 100 places of injury and 200 control sites between December 1991 and December 1993. RESULTS: The volume of traffic (odds ratio [OR] = 2.16 for an increase of 100 vehicles per hour) in combination with the proportion of vehicles exceeding the speed limit (OR = 1.04) for each 1% increase in average speed, and the presence of footpaths (OR = 11.0) were associated with significant increase in the risk of injury. A graded inverse relationship was present between socioeconomic status and the odds of pedestrian injury. CONCLUSIONS: These findings have obvious implications for public health as features of the physical environment are potentially modifiable.

Visual outcomes in the subfoveal radiotherapy study: a randomized controlled trial of teletherapy for age-related macular degeneration.

OBJECTIVE: To determine whether teletherapy with 6-mV photons can reduce visual loss in patients with subfoveal choroidal neovascularization in age-related macular degeneration. DESIGN: A multicenter, single-masked, randomized controlled trial of 12 Gy of external beam radiation therapy delivered to the macula of an affected eye vs observation only. SETTING: Three United Kingdom-based hospital units. PARTICIPANTS: Patients with age-related macular degeneration, aged 60 years and older, who had subfoveal choroidal neovascularization and a visual acuity of 20/200 (logMAR 1.0) or better. METHODS: Two hundred three patients were randomly assigned to radiotherapy or observation. Treatment was undertaken at designated radiotherapy centers, and patients assigned to the treatment group received a total dosage of 12 Gy of 6-mV photons in 6 fractions. Follow-up was scheduled at 3, 6, 12, and 24 months. After excluding protocol violators, the data from 199 patients were analyzed. MAIN OUTCOME MEASURES: The primary outcome measure was mean loss of distance visual acuity in the study eye at 12 and 24 months. Other outcome variables analyzed were near visual acuity and contrast sensitivity. The proportions of patients losing 3 or more or 6 or more lines of distance and near acuity and 0.3 or more or 0.6 or more log units of contrast sensitivity at each follow-up were also analyzed. RESULTS: At all time points, mean distance visual acuity was better in the radiotherapy-treated group than in the control group, but the differences did not reach statistical significance. At 24 months, analysis of the proportions of patients with loss of 3 or more (moderate) (P =.08) or 6 or more (severe) (P =.29) lines of distance vision showed that fewer treated patients had severe losses, but there was no statistically significant difference between groups. For near visual acuity, although there was no evidence of treatment benefit at 12 and 24 months, a significant difference in favor of treatment was present at 6 months (P =.048). When analyzed by the proportions of patients losing 3 lines of contrast sensitivity, there was a significant difference in favor of treatment at 24 months (P =.02). No adverse retinal effects were observed during the study, but transient disturbance of the precorneal tear film was noted in treated patients. CONCLUSION: The results of the present trial do not support the routine clinical use of external beam radiation therapy in subjects with subfoveal choroidal neovascularization in age-related macular degeneration.

A vision specific functional index for use in patients with age related macular degeneration.

AIM: To develop and evaluate a new vision specific functional index for use in individuals with age related macular degeneration (AMD). METHODS: Following consultation with patients with AMD and healthcare professionals, a questionnaire entitled the Daily Living Tasks Dependent on Vision (DLTV) was constructed. It was administered by interview to three separate groups of individuals aged 50 years or older: people with AMD, people with cataract, and people with no visual disability. The relations between DLTV, distance visual acuity, and disorder were examined using Pearson's product moment correlation coefficients, stepwise regression, and principal component analysis. RESULTS: There was a positive correlation between DLTV items and distance visual acuity in the better eye. Principal component analysis showed that the DLTV has a major single dimension within it. This first principal component accounted for 59% of the variation and correlated well with distance visual acuity in the better eye. Other components were found, one of which correlated with the difference in vision in the two eyes and one which featured in the differentiation of AMD subjects from individuals with cataracts. CONCLUSIONS: The DLTV provided information on visual impairment in patients over and above that obtained from a measure of visual acuity. It also showed that patients with AMD experience greater difficulty with daily living tasks for any given level of acuity than do patients with cataract.

Reduced vision in older adults with age related macular degeneration interferes with ability to care for self and impairs role as carer.

AIM: To study the relation between visual impairment and ability to care for oneself or a dependant in older people with age related macular degeneration (AMD). METHOD: Cross sectional study of older people with visual impairment due to AMD in a specialised retinal service clinic. 199 subjects who underwent visual function assessment (fully corrected distance and near acuity and contrast sensitivity in both eyes), followed by completion of a package of questionnaires dealing with general health status (SF36), visual functioning (Daily Living Tasks Dependent on Vision, DLTV) and ability to care for self or provide care to others. The outcome measure was self reported ability to care for self and others. Three levels of self reported ability to care were identified--inability to care for self (level 1), ability to care for self but not others (level 2), and ability to care for self and others (level 3). RESULTS: People who reported good general health status and visual functioning (that is, had high scores on SF36 and DLTV) were more likely to state that they were able to care for self and others. Similarly people with good vision in the better seeing eye were more likely to report ability to care for self and others. People with a distance visual acuity (DVA) worse than 0.4 logMAR (Snellen 6/15) had less than 50% probability of assigning themselves to care level 3 and those with DVA worse than 1.0 logMAR (Snellen 6/60) had a probability of greater than 50% or for assigning themselves to care level 1. Regression analyses with level of care as the dependent variable and demographic factors, DLTV subscales, and SF36 dimensions as the explanatory variables confirmed that the DLTV subscale 1 was the most important variable in the transition from care level 3 to care level 2. The regression analyses also confirmed that the DLTV subscale 2 was the most important in the transition from care level 3 to care level 1. CONCLUSIONS: Ability to care for self and dependants has a strong relation with self reported visual functioning and quality of life and is adversely influenced by visual impairment. The acuity at which the balance of probability shifts in the direction of diminished ability to care for self or others is lower than the level set by social care agencies for provision of support. These findings have implications for those involved with visual rehabilitation and for studies of the cost effectiveness of interventions in AMD.

Macular degeneration: do conventional measurements of impaired visual function equate with visual disability?

AIMS: To examine the relation between measures of vision and ability to perform daily living tasks in those visually impaired with macular degeneration. METHODS: A visual functioning index (daily living tasks dependent on vision: DLTV) was used to evaluate patients' perception of their ability to perform vision dependent tasks. Distance visual acuity, near visual acuity, reading speed, and contrast sensitivity were measured in all patients. In addition, a new measure of reading ability was derived, designated the reading index. This takes into account both the size of the text read and the time to read it and is equivalent to the reading speed in words per minute divided by text size in M. RESULTS: The reading index was found to show best associations with the majority of items within the DLTV. Stepwise regression identified the combination of reading index and distance visual acuity as having the best associations with DLTV items. The present study also demonstrated that specific levels of vision as measured by acuity, reading index, and contrast sensitivity corresponded with different perceived amounts of difficulty in the performance of daily living tasks. CONCLUSIONS: This study showed that reading index is valuable in predicting the ability to perform daily living tasks and therefore may be useful in the visual assessment of the visually impaired individual. In addition, this study identified specific levels of vision at which individuals reported different degrees of difficulty in performing daily living tasks.

CNV subtype in first eyes predicts severity of ARM in fellow eyes.

AIM: To examine the relation between the type of choroidal neovascularisation (CNV) in the first eye and age related maculopathy (ARM) severity in the fellow eye. METHODS: Colour fundus photographs and fluorescein angiograms from 67 subjects with a clinical diagnosis of CNV in one eye were scrutinised. CNV was classified as wholly classic, predominantly classic, minimally classic, or occult based on the proportion of classic leakage within the lesion. ARM changes in the fellow eye were assigned a severity stage using the system described by the Rotterdam Eye Study. Logistic regression analysis was employed to examine the association between CNV subtype and ARM stage. RESULTS: Of subjects with classic or predominantly classic CNV in the first eye 78% exhibited least no or early ARM features in the fellow eye. By contrast, 85% of subjects with minimally classic or occult CNV in the first eye exhibited more advanced ARM features in the fellow eye. Kruskall-Wallis one way ANOVA by ranks showed that this was highly significant (p = 0.002). Logistic regression analysis showed that as the proportion of occult CNV increased in the first eye, fellow eyes of subjects in this category were more likely to have been assigned to a higher ARM stage (p = 0.019). The area occupied by the CNV in the first eye also influenced severity of ARM changes in the fellow eye. CONCLUSION: The type and extent of CNV in the first affected eye has a distinct relation to ARM severity in the fellow eye. Fellow eyes of subjects with minimally classic or occult CNV in the first affected eye show widespread ARM changes suggestive of retinal pigment epithelial dysfunction. These findings suggest that classic CNV may be focal disease while occult CNV is essentially a more widespread retinal pigment epithelial disorder.

Behavioural factors as predictors of motor vehicle crashes: differentials between young urban and rural drivers.

OBJECTIVE: To describe the driver and behavioural factors that predispose young drivers to crash in the first 12 months of driving and to compare whether these factors differ between young urban and rural drivers. METHODS: A cohort comprising 1,796 newly licensed urban and rural drivers from Western Australia was recruited and followed over the first 12 months of driving. Using Cox proportional hazard analysis, driver and behavioural factors were assessed to determine whether they predicted the likelihood of a crash. RESULTS: The incidence rate for a motor vehicle crash was marginally higher for urban drivers compared with rural drivers (Urban: IR=4.2/10,000 driving days; Rural: IR=3.7/10,000 driving days). There was no significant difference in the time to crash between urban and rural drivers. Two factors, namely the frequency of driving before obtaining a learner-driver permit and the driver's level of risk taking, were significantly associated with a motor vehicle crash in the first year of driving. CONCLUSION: Irrespective of whether the driver is licensed in a rural or urban area, high risk-taking drivers are at an elevated risk of a motor vehicle crash in the first 12 months of driving. IMPLICATIONS: Aspects of Graduated Driver Training and Licensing Programs (GDTLP) could be effective in targeting this at-risk group.

At risk in two worlds: injury mortality among indigenous people in the US and Australia, 1990-92.

This paper outlines the commonalties and unique differences in injury experience among the indigenous people in the United States and Australia. Injury mortality rates among Indigenous people in the United States and Australia are approximately 2-3 times greater than rates for the non-Indigenous population in each country. Motor vehicle-related injuries accounted for one-third of the injury deaths for Native Americans and Australian Aboriginals. Suicide accounted for more deaths in Native Americans (15.5 per 100,000) than it did for Australian Aboriginals (11.1 per 100,000), whereas the injury death rate in Australian Aboriginals due to poisoning was almost twice that of Native Americans. Culturally appropriate interventions tailored to specific local settings and problems will be necessary to reduce injury mortality among Indigenous people.

Walking to school and traffic exposure in Australian children.

Daily patterns of pedestrian activity in young children have important health implications, primarily because of the risk of road traffic injury, but also because they may reflect the commencement of exercise habits with long-term consequences. A cross-sectional survey in two Australian cities, Melbourne and Perth, aimed to collect, by parent self-administered questionnaire, population-based data on modes of travel, numbers of street crossings (both accompanied and unaccompanied by an adult), and sociodemographic factors for six- and nine-year-old children. Results indicate that 35 per cent (95 per cent confidence interval (CI) 31 to 39 per cent) and 31 per cent (CI 28 to 34 per cent) walk to school in Melbourne and Perth respectively, while over 60 per cent are driven to school by car, with very small proportions riding bicycles or taking public transport. A higher level of walking was associated with lower levels of several indicators of socioeconomic status. Logistic regression analysis showed that the strongest predictor of walking activity was school type (government versus independent), and after adjusting for this, lesser car ownership, non-English-speaking background and lower occupational category were associated with walking to school, while a different set of predictors--age, sex and maternal education--was associated with the unaccompanied crossing of streets. There was little difference in overall walking levels between boys and girls, but boys were significantly more likely to cross streets unaccompanied (adjusted odds ratio 1.41, CI 1.14 to 1.72), providing a partial explanation of documented sex differences in injury rates.

The validity of children's self-reported exposure to traffic.

This paper reports on a series of studies of the validity of children's self-reported exposure to traffic. The studies were conducted within a larger case-control study carried out in the metropolitan area of Perth, Western Australia. For these validity studies, subjects were randomly selected from the original pool of case (n = 100) and control (n = 400) subjects. Three techniques were used to assess the validity of the self-reported 'habitual exposure', namely, the 'moving observer' technique, pedestrian diaries, and a test of construct validity. The child's regular walking activities during the course of a typical week was considered the child's 'habitual exposure'. The 'moving observer' technique involved either the researcher or research assistant following a random sample of children on their walking trips. A further sample of children maintained a 'diary' of their weekly walking trips, and a number of constructs, in this case variables which related, indirectly, to the child's level of exposure to the road environment, were included in the interview schedule. As two researchers were involved in all aspects of this study, intra- and inter-rater reliability were assessed and tape-recordings of the interviews were used to determine the reliability of the coded data. No significant differences were found between the child's reported exposure to the road environment and either the observed exposure or exposure recorded in pedestrian diaries. For some exposure variables, namely, the number and duration of walking trips, children tended to underestimate their exposure (when compared to the observations of the researchers). For case subjects, the number of roads crossed was also underestimated. The test of construct validity indicated that time spent in 'out-of-home activities' (activities other than going to or from school, which involved time spent in the road environment) does not correlate strongly with 'habitual exposure'. Intra- and inter-rater reliability and the reliability of transcribed data from taped interviews were all found to be very sound. The studies indicate that children's self-reported 'habitual exposure' data is a valid measure of his or her actual exposure in the road environment.

Validation of an outcome scale for use in adult psychiatric practice.

OBJECTIVE: To clarify the usefulness, acceptability, sensitivity, and validity of version 4 of the Health of the Nation Outcome Scale (HoNOS), a scale developed to meet the requirement for a clinically acceptable outcome scale for routine use in mental illness services. DESIGN: Patients with a range of mental illnesses were rated on the HoNOS at the beginning and end of an episode by interviews with mental health professionals. SUBJECTS: 934 patients from eight diagnostic categories were rated by 129 mental health professionals at 17 sites; 250 were also rated on a range of comparison scales. OUTCOME MEASURES: Comparison of patients' scores at the beginning and end of an episode using individual item scores, dimensional subscores, and the total score. RESULTS: HoNOS scores decreased by almost 50% between the beginning and end of episodes. They varied with the severity of the setting and discriminant analysis showed that the HoNOS had a moderate level of discriminatory power. Correlation analysis showed acceptable levels of agreement with independent scales, although the accuracy of ratings of some items at the beginning of an episode was affected by information deficits. CONCLUSION: The findings indicate that HoNOS is sensitive to change across time and to differences in illness type and severity, and has a sufficient degree of both construct and criterion related validity to fulfil the requirements of a mental health outcome scale for routine use in clinical settings.