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.

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.

Design of a bio-mathematical prediction model using serum tumor markers and immunohistochemistry in peritoneal carcinomatosis with ovarian involvement: a pilot study.

The diagnosis of disseminated intra-abdominal malignancy in women with ovarian involvement can be problematic. Whilst both blood tumor markers and use of immunohistochemical staining on tissue can help decide the origin of the tumor, this is done separately. This study looked at the blood and tissue marker profiles of 198 cases of disseminated malignancy to construct a model, which may help to determine tumor origin. The original histology material from 198 cases of disseminated intra-abdominal epithelial malignancy were reviewed, blind, and reassessed as to the likely site of origin. These cases had immunohistochemical (IHC) staining for cytokeratins (CK) 7 and 20, carcinoembryonic antigen (CEA) and CA125. Blood values for CEA and CA125 were also known at diagnosis. The histologic types of the tumors in this pilot study were of ovarian type morphologically in 130 cases (65.7%), nonovarian in 32 (16.1%), and not assigned in 36 cases (18.2%). The majority of the nonovarian cases were of mucinous type or too poorly differentiated to classify. Analysis showed an overall sensitivity and specificity of 93% and 69%, and positive predictive and negative predictive value of 92% and 71%, respectively, for a diagnosis of ovarian vs nonovarian origin using histology alone vs histology and IHC. Use of an ordinal regression developed a model which uses tissue staining for CK 7 and CEA along with blood levels of CEA to help determine the site of tumor origin.

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.

A cohort study of 20,822 young drivers: the DRIVE study methods and population.

BACKGROUND AND OBJECTIVE: Research on young drivers directly linking risk factors to serious injury and death outcomes is required. The DRIVE Study was established to facilitate this aim. This paper outlines the study methods and describes the population that has been recruited, in order to demonstrate that the necessary heterogeneity in risk factors has been attained. DESIGN, SETTING AND PARTICIPANTS: Drivers aged 17-24 years holding their first-stage provisional driver's licence from New South Wales, Australia, were recruited into a prospective cohort study. The participants were contacted by mail and asked to complete the study questionnaire at an online site or via a mailed questionnaire. Baseline data collection involved a questionnaire with questions to drivers about their training, risk perception, driver behavior, sensation-seeking behavior and mental health. Participants gave consent for prospective data linkage to their data on licensing, crashes and injuries, held in routinely collected databases. RESULTS: 20 822 drivers completed the baseline questionnaire, of whom 45.4% were men, 74.3% resided in capital cities and 25.7% in regional or remote areas. The recruited study population showed a wide variation in the risk factors under examination. For example, almost 40% of drivers reported drinking alcohol at hazardous levels and about 32% of participants seemed to be at a high or very high risk of psychological distress. Participants reported a mean of 67.3 h (median 60 h) of supervised driver training while holding their learner's permit. CONCLUSIONS: The DRIVE Study has a robust study design aimed at minimizing bias in the collection of outcome data. Analyses of baseline data showed substantial heterogeneity of risk factors in the study population. Subsequent prospective linkages comparing relative differences in exposures at baseline with the outcomes of interest have the potential to provide important new information needed to develop targeted interventions aimed at young drivers.

Prevalence of helmet use among motorcycle riders in Vietnam.

OBJECTIVES: To investigate the rate of helmet use among motorcycle drivers in Hai Duong province of Vietnam during winter/spring 2005, and to compare the rates of helmet use by road types. METHOD: Population-based observational surveys. RESULTS: 16,560 motorcyclists were observed across 37 road sites (incorporating 5 road categories). The overall weighted average of helmet use for motorcyclists was 29.94%, with male drivers more likely to wear helmets than female drivers (odds ratio (OR) 1.64, 95% confidence interval (CI) 1.53 to 1.76). Male pillion passengers were less likely to wear helmets than female pillion passengers (OR 0.78, 95% CI 0.72 to 0.85). The number of adult drivers using helmets is larger as compared with that of young drivers (OR 8.56, 95% CI 5.93 to 12.19). The rates of helmet use were significantly higher (p<0.001) on compulsory roads and were 59.01%, 39.97%, 24.22%, 12.7% and 9.54% for national, provincial, district, commune and Hai Duong inner-city roads, respectively. CONCLUSION: Helmet legislation has increased the rate of helmet use by motorcycle drivers on compulsory roads. Elsewhere, rate of helmet use is very low, indicating that in the absence of legislation and enforcement, motorcyclists in Vietnam will not wear a helmet.

The impact of driver distraction on road safety: results from a representative survey in two Australian states.

OBJECTIVE: To quantify the prevalence and effects of distracting activities while driving. DESIGN: Cross sectional driver survey. SETTING: New South Wales and Western Australia, Australia. PARTICIPANTS: 1347 licensed drivers aged between 18 and 65 years. Data were weighted to reflect the corresponding driving population. MAIN OUTCOME MEASURES: Prevalence of distracting activities while driving; perceived risks and adverse outcomes due to distractions. RESULTS: The most common distracting activities during the most recent driving trip were lack of concentration (weighted percentage (standard error, SE) 71.8% (1.4%) of drivers); adjusting in-vehicle equipment (68.7% (1.5%)); outside people, objects or events (57.8% (1.6%)); and talking to passengers (39.8% (1.6%)). On average, a driver engaged in a distracting activity once every six minutes. One in five crashes (21%) during the last three years, involving one in 20 drivers (5.0% (0.7%)), was attributed to driver distraction based on self-report. In the population under study, this equated to 242,188 (SE 34,417) drivers. Younger drivers (18-30 years) were significantly more likely to report distracting activities, to perceive distracting activities as less dangerous, and to have crashed as a result. CONCLUSIONS: Distracting activities while driving are common and can result in driving errors. Driver distraction is an important cause of crashes. Further research is needed to estimate the risk conferred by different distracting activities and the circumstances during which activities pose greatest risk. These results suggest that a strategy to minimize distracting activities while driving, with a focus on young drivers, is indicated.

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.

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.

The effect of nicotine on basophil histamine release.

BACKGROUND: Changes in the immune and inflammatory response are induced by smoking tobacco but underlying mechanisms remain to be elucidated. OBJECTIVE: This study investigated the effect of nicotine agonists on histamine release from human basophils. METHODS: Peripheral blood basophils were obtained from healthy volunteers. The effect of the nicotine agonists [-]-1-methyl-2-[3-pyridyl]pyrrolidine and (+)-nicotine di-p-toluoyltartrate salt on cell viability and anti-IgE induced histamine release was investigated. RESULTS: Cell viability was not altered by preincubation with the agents for 15 min. Anti-IgE induced histamine release was significantly inhibited by preincubation (15 min, 37 degrees C) with [-]-1-methyl-2-[3-pyridyl]pyrrolidine at the highest concentration tested 10(-)3 M (p<0.01). Preincubation (15 min, 37 degrees C) with (+)-nicotine di-p-toluoyltartrate salt significantly inhibited anti-IgE induced histamine release at 10(-3)M and 10(-5) M (p<0.05). CONCLUSIONS: This study has demonstrated that nicotine agonists inhibit histamine release from human basophils. Further studies examining the effect of smoking on basophil activation are required.

Community-based study of the association of high myopia in children with ocular and systemic disease.

PURPOSE: High myopia in childhood is associated with important ocular and systemic conditions. However in the UK, high myopia in early childhood is not specifically identified in current ophthalmology, optometry, or orthoptic protocols for screening, referral, or investigation. An ongoing study in the West Midlands, UK, is investigating high myopia presenting to community health care clinics with the aim of compiling guidelines for assessment and subsequent referral. METHODS: Children with high myopia were identified from community optometric and orthoptic sources and invited for an ophthalmology and optometry examination to ascertain possible ocular or systemic disease. RESULTS: High myopia with no associated ocular or systemic condition was present in 15 (56%) of the children. In seven children (25%), associated ocular problems were found including unrecognized retinal dystrophies and amblyopia. Systemic disorders associated with high myopia were found in five children (19%) and included Sticklers syndrome, Weill-Marchesani syndrome, and homocystinuria. In one child, the diagnosis made before this study was found to be incorrect, and in another child, the results were inconclusive. In two cases, the diagnosis of a systemic condition in the child led to the identification of the disease in at least one relative. CONCLUSIONS: There is a high prevalence of ocular and systemic abnormality in young children seen in the community. Optometric and ophthalmologic assessment of children less than 10 years with myopia > or =5 D is likely to identify significant ocular or systemic disease, a proportion of which will respond to medical intervention. Detection and prompt referral of these cases by community health care services may be expected to prolong vision and possibly life expectancy.

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.

Smoking, atopy and certain furry pets are major determinants of respiratory symptoms in children: the International Study of Asthma and Allergies in Childhood Study (Ireland).

BACKGROUND: Environmental, cultural and health care differences may account for variation among countries in the prevalence of asthma and respiratory symptoms in teenagers. OBJECTIVE: To examine the prevalence of respiratory symptoms and the level of diagnosis, and to compare determinants of asthma and severe wheeze in two countries. METHODS: Self-completion questionnaires based on the International Study of Asthma and Allergies in Childhood (ISAAC) protocol were provided to school children in Ireland (Republic and Northern Ireland). In the Republic of Ireland, all children in classes largely aged 13-14 years from 30 post-primary schools were selected by random sampling stratified by school size, composition and Health Board in Spring 1995. In Northern Ireland, all children largely aged 13-14 years of age from 26 post-primary schools were selected by random sampling stratified by school type, composition and Education and Library Board in Spring 1996. RESULTS: Questionnaires were completed by 2,364 children from Northern Ireland and 2,671 from the Republic, about 90% of those eligible to participate. The prevalences of wheeze at various levels of severity, of diagnosed asthma and of treated wheeze were very similar in Northern Ireland and the Republic of Ireland. A significant proportion of those reporting more severe symptomatology (four or more attacks of wheeze in the past 12 months and/or one or more nights disturbed and/or moderate or greater disruption of daily activities and/or speech restriction due to wheeze) had been neither diagnosed nor treated for asthma (20-37%). To investigate the determinants of the more severe symptomatology of asthma or treated wheeze a series of stepwise multiple regression analyses was performed. A history of atopy, cigarette smoking, the possession of a furry pet other than a dog or cat and age were each independently associated with severe wheeze, whilst atopy, a furry pet (as above) and gender were each independently associated with asthma or treated wheeze. CONCLUSIONS: Cigarette smoking is closely associated with the reporting of significant respiratory symptoms together with atopy and exposure to furry pets. Some 20-37% of severe symptoms were neither diagnosed nor treated as asthma.

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.

Improvements in measures of vision and self-reported visual function after cataract extraction in patients with late-stage age-related maculopathy.

PURPOSE: A recent study indicated that patients with cataracts and early age-related maculopathy may benefit from cataract extraction. To ascertain whether cataract extraction in the presence of concurrent advanced age-related maculopathy was also associated with a clear benefit, we studied visual function and self-reported visual functioning in a cohort of 12 patients pre- and post-phakoemulsification. METHODS. All 12 patients had a diagnosis of advanced age-related maculopathy in the eye scheduled for cataract surgery. Preoperative assessment included refraction and recording of best corrected distance and near acuity and contrast sensitivity in both eyes. The Daily Living Tasks Dependent on Vision questionnaire was administered. After phakoemulsification and intraocular lens implantation, all patients were reviewed and assessed. RESULTS: After surgery, improvement in acuity was recorded in nine operated eyes, whereas acuity remained unchanged in three eyes. Improvement in contrast sensitivity in the operated eye occurred in 10 patients, but in two patients contrast was reduced postoperatively. In terms of self-reported visual functioning, improvement in the ability to undertake many daily living tasks dependent on vision was recorded after cataract surgery. CONCLUSIONS: Significant improvements in specific areas of self-reported visual functioning and measures of vision were recorded after cataract surgery. During the follow-up period, none of the operated eyes suffered a fall in visual acuity. There was also no evidence of worsening of the pre-existing macular lesion as judged by clinical examination and fundus photography.

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.