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L Sheppard

Publications and source records attributed to L Sheppard.

At least 19 recordsLinked to original sources
PubMed2007

The interpretation of exposure effect estimates in chronic air pollution studies.

In this article we consider the interpretation of regression parameters used to represent 'chronic' or 'long-term' air pollution exposure effects. Although scientific interest typically lies in understanding such effects at the level of the individual, studies have generally employed a semi-ecological design; outcomes and confounder information are collected on individuals while exposure is only available at the aggregate-or group-level. A precise interpretation of results from a semi-ecological design must take into account the aggregated nature, both spatial and temporal, of the exposure measure. The most common analysis approach for assessing chronic exposure effects has been within the Cox proportional hazards model framework; specific analyses are tailored to accommodate the shortcomings of the available exposure information. We revisit the underlying assumptions of the Cox model and discuss the implications of two common aspects of chronic effects studies: time-dependent exposures and time-varying effects. Focusing on the consequences of temporal aggregation of exposure, we show that an estimate obtained from a time-aggregated semi-ecological design can correspond to very different underlying time-varying exposure and risk scenarios. Further, distinguishing which of these is correct is not possible from the semi-ecological data alone. Our goal is to highlight some statistical issues faced by existing studies of chronic air pollution effects, and aid in the development and planning of future studies.

Air Pollution↗
PubMed2006

The effects of growth hormone treatment on health-related quality of life in children.

BACKGROUND/AIMS: The effects of growth hormone deficiency (GHD) on linear growth in children are well documented, but there is less convincing evidence regarding the impact on health-related quality of life (QOL). We examined QOL in children aged 8-16 years with acquired GHD following treatment for malignancy (AGHD) or idiopathic GHD (IGHD) on commencing growth hormone treatment (GHT) over 6 months. We adopted a longitudinal design involving consecutive patients and their families attending clinic over an 18-month period. Mothers and children were invited to complete questionnaires before GHT (T1) and 6 months later (T2). METHODS: Mothers of 22 children (AGHD n = 14; IGHD n = 8) completed standardized measures of child QOL and behaviour. Children completed parallel measures of QOL, short-term memory tasks and fitness either in clinic or at the family home. RESULTS: For children with AGHD, QOL was significantly below population norms at T1 and improved over time. For children diagnosed with IGHD, QOL at T1 was below, but comparable with population norms. QOL improved over time, though not significantly. CONCLUSION: GHT is potentially valuable for improving QOL in children, especially in cases of AGHD. We conclude that benefits of GHT for QOL need to be evaluated independent of different diagnostic groups.

Adolescent↗
PubMed2006

International Programme for Resource Use in Critical Care (IPOC)--a methodology and initial results of cost and provision in four European countries.

BACKGROUND: A standardized top-down costing method is not currently available internationally. An internally validated method developed in the UK was modified for use in critical care in different countries. Costs could then be compared using the World Health Organization's Purchasing Power Parities (WHO PPPs). METHODS: This was an observational, retrospective, cross-sectional, multicentre study set in four European countries: France, UK, Germany and Hungary. A total of 329 adult intensive care units (ICUs) participated in the study. RESULTS: The costs are reported in international dollars ($) derived from the WHO PPP programme. The results show significant differences in resource use and costs of ICUs over the four countries. On the basis of the sum of the means for the major components, the average cost per patient day in UK hospitals was $1512, in French hospitals $934, in German hospitals $726 and in Hungarian hospitals $280. CONCLUSIONS: The reasons for such differences are poorly understood but warrant further investigation. This information will allow us to better adjust our measures of international ICU costs.

Costs and Cost Analysis↗
PubMed2006

The contribution of a comprehensive stroke unit to the outcome of Chinese stroke patients.

INTRODUCTION: There are significant differences in stroke patterns and risk factors for cerebrovascular disease between Chinese subjects and Caucasians. The outcome of stroke unit care in a Chinese population has not been described in the medical literature. The present study aims to evaluate the outcome of stroke unit care in Chinese subjects. METHODS: By prospective comparative research, Chinese patients treated in the stroke unit were group-matched with those treated in the general medical ward by age, gender, premorbid functional status (by the Barthel Index), National Institute of Health Stroke Scale score, and stroke types. From April 2001 to April 2002, a total of 188 patients in the stroke unit group and 177 patients in the general ward group were recruited in the study. The main outcome measures included mortality at 28 and 120 days, and the length of inpatient stay. RESULTS: Stroke unit care significantly reduced mortality of patients with acute stroke after 28 and 120 days. After 28 days, mortality was 3.3 percent and 17.2 percent for the stroke unit group and general ward group, respectively (p-value is equal to or less than 0.01); whereas after 120 days, mortality was 5.0 percent and 24.7 percent for the stroke unit group and general ward group, respectively (p-value is equal to or less than 0.001). The stroke unit care was demonstrated, by logistic regression analysis, to have contributed to the reduction of mortality at 120 days (p-value is 0.014). At 28 days, there was only a trend for stroke unit care to contribute to the reduction of mortality by logistic regression analysis (p-value is 0.067). By Kaplan-Meier survival curves (log rank statistic is 10.46, p-value is 0.001) and a Cox regression (hazard ratio 0.253, 95 percent confidence interval 0.085 to 0.754, p-value is 0.014), the stroke unit care was further found to reduce mortality significantly. The mean length of inpatient stay of the stroke unit group was 37.1 days, while that of the general medical ward group was 69.3 days (p-value is equal to or less than 0.001). CONCLUSION: Chinese subjects receiving comprehensive stroke unit care are associated with less mortality and shorter length of hospital stay than those having conventional care in general medical wards.

Acute Disease↗
PubMed2005

Prospective noise induced changes to hearing among construction industry apprentices.

AIMS: To characterise the development of noise induced damage to hearing. METHODS: Hearing and noise exposure were prospectively monitored among a cohort of newly enrolled construction industry apprentices and a comparison group of graduate students, using standard pure tone audiometry and distortion product otoacoustic emissions (DPOAEs). A total of 328 subjects (632 ears) were monitored annually an average of 3.4 times. In parallel to these measures, noise exposure and hearing protection device (HPD) use were extensively monitored during construction work tasks. Recreational/non-occupational exposures also were queried and monitored in subgroups of subjects. Trade specific mean exposure L(eq) levels, with and without accounting for the variable use of hearing protection in each trade, were calculated and used to group subjects by trade specific exposure level. Mixed effects models were used to estimate the change in hearing outcomes over time for each exposure group. RESULTS: Small but significant exposure related changes in DPOAEs over time were observed, especially at 4 kHz with stimulus levels (L1) between 50 and 75 dB, with less clear but similar patterns observed at 3 kHz. After controlling for covariates, the high exposure group had annual changes in 4 kHz emissions of about 0.5 dB per year. Pure tone audiometric thresholds displayed only slight trends towards increased threshold levels with increasing exposure groups. Some unexpected results were observed, including an apparent increase in DPOAEs among controls over time, and improvement in behavioural thresholds among controls at 6 kHz only. CONCLUSIONS: Results indicate that construction apprentices in their first three years of work, with average noise exposures under 90 dBA, have measurable losses of hearing function. Despite numerous challenges in using DPOAEs for hearing surveillance in an industrial setting, they appear somewhat more sensitive to these early changes than is evident with standard pure tone audiometry.

Adult↗
PubMed2004

The cost of a hospital ward in Europe: is there a methodology available to accurately measure the costs?

Costing health care services has become a major requirement due to an increase in demand for health care and technological advances. Several studies have been published describing the computation of the costs of hospital wards. The objective of this article is to examine the methodologies utilised to try to describe the basic components of a standardised method, which could be applied throughout Europe. Cost measurement however is a complex matter and a lack of clarity exists in the terminology and the cost concepts utilised. The methods discussed in this review make it evident that there is a lack of standardized methodologies for the determination of accurate costs of hospital wards. A standardized costing methodology would facilitate comparisons, encourage economic evaluation within the ward and hence assist in the decision-making process with regard to the efficient allocation of resources.

Cost Allocation↗
PubMed2004

Accuracy of task recall for epidemiological exposure assessment to construction noise.

AIMS: To validate the accuracy of construction worker recall of task and environment based information; and to evaluate the effect of task recall on estimates of noise exposure. METHODS: A cohort of 25 construction workers recorded tasks daily and had dosimetry measurements weekly for six weeks. Worker recall of tasks reported on the daily activity cards was validated with research observations and compared directly to task recall at a six month interview. RESULTS: The mean L(EQ) noise exposure level (dBA) from dosimeter measurements was 89.9 (n = 61) and 83.3 (n = 47) for carpenters and electricians, respectively. The percentage time at tasks reported during the interview was compared to that calculated from daily activity cards; only 2/22 tasks were different at the nominal 5% significance level. The accuracy, based on bias and precision, of percentage time reported for tasks from the interview was 53-100% (median 91%). For carpenters, the difference in noise estimates derived from activity cards (mean 91.9 dBA) was not different from those derived from the questionnaire (mean 91.7 dBA). This trend held for electricians as well. For all subjects, noise estimates derived from the activity card and the questionnaire were strongly correlated with dosimetry measurements. The average difference between the noise estimate derived from the questionnaire and dosimetry measurements was 2.0 dBA, and was independent of the actual exposure level. CONCLUSIONS: Six months after tasks were performed, construction workers were able to accurately recall the percentage time they spent at various tasks. Estimates of noise exposure based on long term recall (questionnaire) were no different from estimates derived from daily activity cards and were strongly correlated with dosimetry measurements, overestimating the level on average by 2.0 dBA.

Adult↗
PubMed2004

Predictors of hearing threshold levels and distortion product otoacoustic emissions among noise exposed young adults.

AIM: To examine the relations between noise exposure and other risk factors with hearing function as measured by audiometric thresholds and distortion product otoacoustic emissions. METHODS: A total of 456 subjects were studied (393 apprentices in construction trades and 63 graduate students). Hearing and peripheral auditory function were quantified using standard, automated threshold audiometry, tympanometry, and distortion product otoacoustic emissions (DPOAEs). The analysis addressed relations of noise exposure history and other risk factors with hearing threshold levels (HTLs) and DPOAEs at the baseline test for the cohort. RESULTS: The cohort had a mean age of 27 (7) years. The construction apprentices reported more noise exposure than students in both their occupational and non-occupational exposure histories. A strong effect of age and years of work in construction was observed at 4, 6, and 8 kHz for both HTLs and DPOAEs. Each year of construction work reported prior to baseline was associated with a 0.7 dB increase in HTL or 0.2 dB decrease DPOAE amplitude. Overall, there was a very similar pattern of effects between the HTLs and DPOAEs. CONCLUSIONS: This analysis shows a relatively good correspondence between the associations of noise exposures and other risk factors with DPOAEs and the associations observed with pure-tone audiometric thresholds in a young adult working population. The results provide further evidence that DPOAEs can be used to assess damage to hearing from a variety of exposures including noise. Clarifying advantages of DPOAEs or HTLs in terms of sensitivity to early manifestations of noise insults, or their utility in predicting future loss in hearing will require longitudinal follow up.

Adult↗
PubMed2003

Exposure to ambient fine particulate matter and primary cardiac arrest among persons with and without clinically recognized heart disease.

The authors studied the association between incidence of primary cardiac arrest and daily measures of fine particulate matter (</=2.5 micro m) using a case-crossover study of 1,206 Washington State out-of-hospital cardiac arrests (1985-1994) among persons with (n = 774) and without (n = 432) clinically recognized heart disease. The authors compared particulate matter levels on the day of the cardiac event and the 2 days preceding the event with levels from matched reference days. The estimated relative risk for a 13.8- micro g/m(3) increase in fine particulate matter (nephelometry: 0.54 x 10(-1) km(-1 )bsp) on the day prior to cardiac arrest was 0.94 (95% confidence interval: 0.88, 1.02). Pollutant levels measured on the same day as the event and on the 2 days preceding the event demonstrated similar results. No increased risk was found among all cases with preexisting cardiac disease (odds ratio = 0.97, 95% confidence interval: 0.89, 1.07); however, an unexpected association appeared between current smokers with preexisting heart disease and increased particulate matter levels 2 days prior to the event (odds ratio = 1.29, 95% confidence interval: 1.06, 1.55). This association was not present in the 0- or 1-day lag analyses or in persons with other diseases. There was no consistent association between increased levels of fine particulate matter and risk of primary cardiac arrest.

Aged↗
PubMed2001

Work practices of rural and remote physiotherapists.

Physiotherapists in rural and remote areas face challenges in their service delivery. The challenge is to provide accessible and comprehensive services to rural and remote Australians. Research was undertaken regarding the work practices of physiotherapists and the availability of other health professionals in rural and remote South Australia and Northern Territory. Rural and remote area physiotherapists in this study are likely to be sole practitioners with a generalist practice. The high number who have practising rights at public hospitals gives rise to service delivery with a wide range of clients and reduced opportunity for specialisation. In addition, the demand for physiotherapists to be multiskilled is increased with the lower number of resident medical specialists and allied health professionals in rural areas. Greater access to other professionals for rural and remote Australians may come from the development of resource networks supported by regional organisation of resources and infrastructure.

Health Services Accessibility↗
PubMed2001

Referent selection in case-crossover analyses of acute health effects of air pollution.

The case-crossover design was proposed for the study of a transient effect of an intermittent exposure on the subsequent occurrence of a rare acute-onset disease. This design can be an alternative to Poisson time series regression for studying the health effects of fine particulate matter air pollution. Characteristics of time-series of particulate matter, including long-term time trends, seasonal trends, and short-term autocorrelations, require that referent selection in the case-crossover design be considered carefully and adapted to minimize bias. We performed simulations to evaluate the bias associated with various referent selection strategies for a proposed case-crossover study of associations between particulate matter and primary cardiac arrest. Some a priori reasonable strategies were associated with a relative bias as large as 10%, but for most strategies the relative bias was less than 2% with confidence interval coverage within 1% of the nominal level. We show that referent selection for case-crossover designs raises the same issues as selection of smoothing method for time series analyses. In addition, conditional logistic regression analysis is not strictly valid for some case-crossover designs, introducing further bias.

Acute Disease↗
PubMed2001

A case-crossover analysis of particulate matter air pollution and out-of-hospital primary cardiac arrest.

Numerous epidemiologic studies have reported increases in the daily incidence of cardiovascular mortality and morbidity associated with increases in daily levels of particulate matter air pollution. We studied the association between the incidence of primary cardiac arrest and two daily measures of particulate matter using a case-crossover study of 362 cases of out-of-hospital cardiac arrest. All cases were attended by paramedics and had no history of clinically recognized heart disease or life-threatening comorbidities. We compared particulate matter levels at index times with particulate matter levels from referent days matched on day of week within strata defined by month and year. The estimated relative risk at a lag of 1 day for an interquartile range (IQR) change in nephelometry (0.51 x 10(-1) km(-1)) was 0.893 (95% CI = 0.779-1.024). The estimated relative risk at a lag of 1 day for an IQR change in PM10 (19.3 microg m(-3)) was 0.868 (95% CI = 0.744-1.012). Other lag periods gave similar results. We did not find evidence of confounding by carbon monoxide or sulfur dioxide. Analysis of effect modification by individual-level variables did not reveal any susceptible subgroups. These findings do no support an association between particulate matter and increased risk of primary cardiac arrest among persons without clinically recognized heart disease. The null results of this study may result from several factors, including the highly selected nature of this case series and the relatively low particulate matter levels in the Seattle metropolitan area.

Adult↗
PubMed2000

Molecular breeding of viruses.

Genetic recombination is a major force driving the evolution of many viruses. Recombination between two copackaged retroviral genomes may occur at rates as high as 40% per replication cycle. This enables genetic information to be shuffled rapidly, leading to recombinants with new patterns of mutations and phenotypes. The in vitro process of DNA shuffling (molecular breeding) mimics this mechanism on a vastly parallel and accelerated scale. Multiple homologous parental sequences are recombined in parallel, leading to a diverse library of complex recombinants from which desired improvements can be selected. Different proteins and enzymes have been improved using DNA shuffling. We report here the first application of molecular breeding to viruses. A single round of shuffling envelope sequences from six murine leukaemia viruses (MLV) followed by selection yielded a chimaeric clone with a completely new tropism for Chinese Hamster Ovary (CHOK1) cells. The composition and properties of the selected clone indicated that this particular permutation of parental sequences cannot be readily attained by natural retroviral recombination. This example demonstrates that molecular breeding can enhance the inherently high evolutionary potential of retroviruses to obtain desired phenotypes. It can be an effective tool, when information is limited, to optimize viruses for gene therapy and vaccine applications when multiple complex functions must be simultaneously balanced.

3T3 Cells↗
PubMed2000

Asthma aggravation, combustion, and stagnant air.

BACKGROUND: The relationship between current concentrations of ambient air pollution and adverse health effects is controversial. We report a meteorological index of air stagnation that is associated with daily visits to the emergency department for asthma in two urban areas. METHODS: Data on daily values of a stagnation persistence index and visits to the emergency department for asthma were collected for approximately two years in Spokane, Washington, USA and for 15 months in Seattle, Washington, USA. The stagnation persistence index represents the number of hours during the 24 hour day when surface wind speeds are less than the annual hourly median value, an index readily available for most urban areas. Associations between the daily stagnation persistence index and daily emergency department visits for asthma were tested using a generalised additive Poisson regression model. A factor analysis of particulate matter (PM(2.5)) composition was performed to identify the pollutants associated with increased asthma visits. RESULTS: The relative rate of the association between a visit to the emergency department for asthma and the stagnation persistence index was 1. 12 (95% CI 1.05 to 1.19) in Spokane and 1.21 (95% CI 1.09 to 1.35) in Seattle for an increase of 11 and 10 hours, respectively, of low wind speed in a given day. The stagnation persistence index was only correlated with one set of factor loadings; that cluster included the stagnation persistence index, carbon monoxide, and organic/elemental carbon. CONCLUSION: Increased air stagnation was shown to be a surrogate for accumulation of the products of incomplete combustion, including carbon monoxide and fine particulate levels of organic and elemental carbon, and was more strongly associated with asthma aggravation than any one of the measured pollutants.

Air Pollutants↗
PubMed2000

Effects of ambient air pollution on symptoms of asthma in Seattle-area children enrolled in the CAMP study.

We observed a panel of 133 children (5-13 years of age) with asthma residing in the greater Seattle, Washington, area for an average of 58 days (range 28-112 days) during screening for enrollment in the Childhood Asthma Management Program (CAMP) study. Daily self-reports of asthma symptoms were obtained from study diaries and compared with ambient air pollution levels in marginal repeated measures logistic regression models. We defined days with asthma symptoms as any day a child reported at least one mild asthma episode. All analyses were controlled for subject-specific variables [age, race, sex, baseline height, and FEV(1) PC(20) concentration (methacholine provocative concentration required to produce a 20% decrease in forced expiratory volume in 1 sec)] and potential time-dependent confounders (day of week, season, and temperature). Because of variable observation periods for participants, we estimated both between- and within-subject air pollutant effects. Our primary interest was in the within-subject effects: the effect of air pollutant excursions from typical levels in each child's observation period on the odds of asthma symptoms. In single-pollutant models, the population average estimates indicated a 30% [95% confidence interval (CI), 11-52%] increase for a 1-ppm increment in carbon monoxide lagged 1 day, an 18% (95% CI, 5-33%) increase for a 10-microg/m(3) increment in same-day particulate matter < 1.0 microm (PM(1.0)), and an 11% (95% CI, 3-20%) increase for a 10-microg/m(3) increment in particulate matter < 10 microm (PM(10)) lagged 1 day. Conditional on the previous day's asthma symptoms, we estimated 25% (95% CI, 10-42%), 14% (95% CI, 4-26%), and 10% (95% CI, 3-16%) increases in the odds of asthma symptoms associated with increases in CO, PM(1.0), and PM(10), respectively. We did not find any association between sulfur dioxide (SO(2)) and the odds of asthma symptoms. In multipollutant models, the separate pollutant effects were smaller. The overall effect of an increase in both CO and PM(1. 0) was a 31% (95% CI, 11-55%) increase in the odds of symptoms of asthma. We conclude that there is an association between change in short-term air pollution levels, as indexed by PM and CO, and the occurrence of asthma symptoms among children in Seattle. Although PM effects on asthma have been found in other studies, it is likely that CO is a marker for vehicle exhaust and other combustion by-products that aggravate asthma.

Adolescent↗
PubMed2000

A case-crossover analysis of fine particulate matter air pollution and out-of-hospital sudden cardiac arrest.

Numerous recent epidemiologic studies report increases in the daily incidence of cardiovascular disease mortality and morbidity related to increases in daily levels of fine particulate matter (PM)* air pollution. This study sought to evaluate the possible association between the occurrence of out-of-hospital sudden cardiac arrest (SCA) and daily PM levels in the Seattle metropolitan area. The underlying hypothesis was that PM exposure may act as a cardiovascular trigger for SCA. A case-crossover study was conducted among 362 SCA cases identified by paramedics from October 1988 through June 1994. Cases were King County WA residents who were married, aged 25 to 74 years at the time of their SCA, with no prior history of clinically recognized heart disease or other life-threatening comorbid conditions. Daily averages of regional PM monitoring data for nephelometry measures of PM (reported in units of bsp, referred to as coefficient of light scattering) and PM10 (particulate matter 10 microm or smaller in aerodynamic diameter) from three monitoring sites were used as indicators of exposure. In the case-crossover analysis, PM levels during index times of cases within the five days preceding an SCA were compared with PM levels at referent days, defined as the same days of the week during the month of SCA occurrence. Lag periods for index days of 0 to 5 days were investigated. The estimated relative risk (RR) at a lag of 1 day for an interquartile range (IQR) change in nephelometry (0.51 bsp) was 0.893 (95% confidence interval [CI] 0.779-1.024). Varying the lag period had only minimal change on the observed association. The estimated relative risk at a lag of 1 day for an IQR change of PM10 (19.3 microg/m3) was 0.868 (95% CI 0.744-1.012). There was no evidence of confounding by ambient daily exposures to carbon monoxide or sulfur dioxide. Analysis of effect modification by individual-level variables, including age, cigarette smoke exposure, physical activity, and other risk or protective factors for cardiovascular disease did not reveal any susceptible subgroups. The null results of this study may be due to several factors; these include: the highly selected nature of this SCA case series; the fact that cases were free of prior clinically recognized heart disease or major life-threatening comorbidity; and the possibility that PM exposures at the relatively low levels seen in the Seattle metropolitan area do not trigger cardiovascular toxic mechanisms that culminate in SCA.

Adult↗