Biomedical subjects
A Lovett
Publications and source records attributed to A Lovett.
Accidents to preschool children: comparing family and neighbourhood risk factors.
Accidental injury in young children is more common among poorer families and in deprived areas but little is known about how these factors interact. This paper describes a study to measure the contribution of individual family factors and area characteristics in determining risk of accidental injury among preschool children. We conducted a population based study of preschool accident and emergency attendances over two years in and around the city of Norwich, UK. Information on individual families was extracted from the district child health information system while "social areas" were constructed from adjacent census enumeration districts with homogeneous social and demographic characteristics. Statistical analysis was by multilevel modelling. Accidental injury rates were much higher in deprived urban neighbourhoods than in affluent areas but the multilevel analysis showed that, for all accidents, much of the variation in rates was accounted for by factors at the individual level i.e. male sex, young maternal age, number of elder siblings and distance from hospital, with a smaller, but independent, influence of living in a deprived neighbourhood. The model for more severe injuries was similar except single parenthood was now significant at the level of individuals and the effect of area deprivation was stronger. We conclude that preschool accidental injuries are influenced by factors operating at both the level of individual families and between areas. This evidence suggests that both social policy changes to improve child care among unsupported young families and targeting accident prevention measures at a local level towards deprived neighbourhoods would reduce accidents.
Effects of distances to hospital and GP surgery on hospital inpatient episodes, controlling for needs and provision.
Age and sex adjusted inpatient episode ratios were calculated from hospital records over a two year period for 555 census wards in Cambridgeshire, Norfolk and Suffolk, UK. Hospital episodes were divided into acute, psychiatric and geriatric specialties, and elective and emergency acute admissions were distinguished. Variations in inpatient episode ratios between wards were compared with census indicators of the 'needs' of local populations for inpatient services, measures of the local provision of hospital and other related services, and measures of the distance to the nearest general practitioner surgery and the distance to the nearest hospital. Hospital episodes were found to be strongly related to both distance measures, but the associations were partially explained by a tendency for the health status of local populations (measured by the needs indicators) to be worst in urban areas close to health services. Including needs and provision variables together with the distance variables explained most of the variations in age and sex adjusted inpatient ratios for small areas. Needs were the most important determinants of emergency acute and psychiatric inpatient rates, but service provision was more important for elective acute and geriatric inpatients. Controlling for needs and provision, distance to hospital produced 17% reduction in acute episodes, 37% reduction in psychiatric episodes and 23% reduction in geriatric episodes over the range of distances observed. Distance to nearest GP surgery reduced elective acute episodes by up to 15% after controlling for confounders. These results demonstrate that the NHS is falling short of its aim to provide fair access to services irrespective of geography, and new policies will be required if geographical inequities are to be reduced.
Effect of labour market conditions on reporting of limiting long-term illness and permanent sickness in England and Wales.
STUDY OBJECTIVE: To identify any bias in the reporting of limiting long term illness and permanent sickness due to labour market conditions, and show the absence of the effect in mortality rates. DESIGN: A geographically based study using data from the 1991 census. Standardised ratios for mortality and long term illness in people aged 0-64 years and permanent sickness in people of working age were compared with Carstairs deprivation scores in multilevel models which separated the effects operating at three geographical scales: census wards, travel to work areas, and standard regions. Holding ward and regional effects constant, variations between travel to work areas were compared with long term unemployment rates. SETTING: Altogether 8690 wards and 262 travel to work areas in England and Wales. MAIN RESULTS: Variations in mortality, limiting long term illness, and permanent sickness were related to Carstairs deprivation scores and standard region. With these relationships controlled, limiting long term illness and permanent sickness were significantly related to long term unemployment levels in travel to work areas, but mortality was not affected. Self reported morbidity was more sensitive to variations in long term unemployment rates in conditions of high social deprivation than in affluent populations. CONCLUSIONS: Limiting long term illness and permanent sickness measures may reflect a tendency for higher positive response in difficult labour market conditions. For average social deprivation conditions, standardised limiting long term illness for people aged 0-64 years was 20% higher in travel to work areas where employment prospects were relatively poor compared with areas with relatively good employment prospects. This casts doubt on the use of limiting long term illness as an indicator of objective health care needs for resource allocation purposes at national level.
Unemployment rate as an updatable health needs indicator for small areas.
BACKGROUND: The objective of the study was to compare updatable unemployment rates with the unemployment rate and composite deprivation indices from the 1991 Census as health needs indicators for small areas. METHODS: Townsend, Carstairs and Jarman indices and male unemployment rates were calculated from the 1991 Census, for 275 wards of the former East Anglian health region with unchanged boundaries between 1981 and 1991. Male unemployment rates were also derived from April 1991 unemployment benefit claimant figures, using both Office of Population Censuses and Surveys mid-year estimates of population and estimates derived from Family Health Services Authority patient registers as the denominator. Ward values were compared using Pearson product moment correlation. RESULTS: All three unemployment measures were closely related to each other and all were broadly as effective in predicting ward variations in mortality and long-term illness in 1991 as the compound deprivation indices of Jarman. Townsend and Carstairs. CONCLUSION: Updatable unemployment rates were as suitable as the composite indices as an indicator of relative health needs for small areas in the year of the Census and might be expected to be superior in inter-censal years.
Factors affecting non-response to cervical cytology screening in Norfolk, England.
A geographic information system was used to integrate information on the uptake of cervical cytology screening for general medical practices in Norfolk with other data on the characteristics of the practices and the population they served. Regression analysis was employed to explore the extent to which variations in non-response were associated with explanatory factors. Non-response to the earlier system of opportunistic screening was found to be associated with the size of practice, the presence of a female doctor, the District Health Authority in which the practice was located, the age structure of the practice population, its degree of socio-economic deprivation and levels of rural remoteness. Compared with the earlier system, the new population-based call and recall system was found to be reaching a larger proportion of the population at risk. The former relationships were weaker under the new system, but non-response was still significantly associated with both social and organisational factors.
Limiting long-term illness and its associations with mortality and indicators of social deprivation.
STUDY OBJECTIVE: To examine geographical variation in limiting long-term illness in England and Wales and assesses the extent of its similarity with the distribution of mortality rates and of deprivation. DESIGN: A geographically based study using data from the 1991 census on limiting long term illness. Maps and regression analysis are used to compare the distribution of standardised illness ratios with standardised mortality ratios and indicators of social deprivation. SETTING: A total of 401 local authority districts in England and Wales. PARTICIPANTS: The population of England and Wales enumerated in the 1991 census. MAIN RESULTS: The geographical pattern of limiting long term illness shows many similarities with that of mortality but there are also some differences. Both are positively associated with indicators of social deprivation, with limiting long term illness tending to show stronger correlations, particularly in the elderly. Most of Wales and many industrial areas of northern England have higher rates of long term illness than would be expected from their mortality rates, while much of south eastern England has lower than expected rates. CONCLUSIONS: Moves towards using data on limiting long term illness instead of standardised mortality rates would have important implications for NHS resource allocations. Further assessment of the reliability of these data on self reported morbidity is required. in particular, there is a need to assess how much they reflect real differences in ill health rather than the influence of socioeconomic or cultural factors affecting the likelihood of a positive answer to the census question on limiting long term illness.
Patients in fundholding and non-fundholding practices.
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Immunodominant T-cell epitopes of rubella virus structural proteins defined by synthetic peptides.
Sets of overlapping synthetic peptides containing predicted T-cell epitope motifs were designed from the murine monoclonal antibody-defined map of linear B-cell epitope domains within each of the structural proteins of rubella virus (RV). The peptides represented well-defined subsequences of two capsid domains (C1 to C29 and C64 to C97), of a domain of glycoprotein E1 containing neutralizing determinants (E1(202) to E1(283), and of a domain of glycoprotein E2 (E2(31) to E2(105). With the exception of peptides representing C64 to C97, each set of peptides stimulated varied but individually specific lymphoproliferative responses in peripheral blood mononuclear cells from 25 to 50% of a representatively large number of normal, RV-immune human donors with diverse human leukocyte antigen (HLA) backgrounds. Responses were mediated by CD4+ T cells in association with HLA class II antigens, though lymphoproliferative responses to a given peptide were usually not HLA-DR allele specific. Correlation analysis of responses to overlapping peptides suggests that there is an immunodominant T-proliferative epitope within C14 to C29 recognized by approximately 50% of the donor population. However, limiting-dilution analysis indicated much variability between individuals in lymphocyte recognition of this T-cell determinant, even within similar HLA-DR contexts. Thus, the fine specificity of relatively immunodominant T-cell epitopes may vary from individual to individual. Synthetic peptides with predicted T-cell motifs have proved to be useful probes of the molecular determinants of cellular immunity to RV and should expand the rational basis for the design of synthetic RV vaccines.
An antibody- and synthetic peptide-defined rubella virus E1 glycoprotein neutralization domain.
We previously described a monoclonal antibody (MAb) library generated by infecting BALB/c mice with rubella virus (RV) and selected by an enzyme-linked immunosorbent assay (ELISA) using purified virion targets. Plasmid pARV02-01, which expresses the fusion protein RecA1-35-GIGDLGSP-E1(202)-E1(283)-GDP-LacZ9-1015 in Escherichia coli, was shown to be a ligand for MAbs E1-18 and E1-20 (J. S. Wolinsky, M. McCarthy, O. Allen-Cannady, W. T. Moore, R. Jin, S. N. Cao, A. Lovett, and D. Simmons, J. Virol. 65:3986-3994, 1991). Both of these MAbs neutralize RV infectivity. A series of five overlapping synthetic peptides was made to further explore the requirements of this MAb binding domain. One of these peptides (SP15; E1(208) to E1(239)) proved an effective ligand for both MAbs in the ELISA. Stepwise synthesis of SP15 defined the minimal amino-terminal requirement for binding MAb E1-18 as E1(221) and that of MAb E1-20 as E1(223); the minimal carboxyl-terminal requirement is uncertain but does not exceed E1(239). Immunization of mice and rabbits with SP15 induced polyvalent antibody reactive with SP15, with other overlapped and related but not unrelated synthetic peptides, and with RV. The rabbit anti-SP15 antibody showed neutralization activity to RV similar to that of MAbs E1-18 and E1-20 but lacked hemagglutination inhibition activity. These data define a neutralization domain on E1 and suggest that the RV epitopes conserved by SP15 may be critical for protective host humoral immune responses.
Monoclonal antibody-defined epitope map of expressed rubella virus protein domains.
An expanded library of murine monoclonal antibodies (MAbs) was generated by infecting BALB/C mice with the Therien strain of rubella virus (RV) and selecting secreting hybrids by enzyme-linked immunosorbent assay (ELISA) using purified virion targets. A panel of plasmids containing specified RV cDNA fragments was also constructed by using a variety of strategies with pGE374- and pGE374-derived expression vectors. Hybrid RecA-RV-beta-galactosidase (LacZ)- or RecA-RV-truncated LacZ-containing proteins collectively representing the entire open reading frame of the structural proteins of RV were overexpressed in Escherichia coli. Bacterial lysates were then probed by ELISA with selected MAbs and by immunoblot following separation by electrophoresis under denaturing conditions. With this approach, MAbs that appeared to react with linear determinants defined epitopes localized within the following domains: MAbs C-1, C-2, and C-8 bind epitopes within the predicted amino-terminal 21 amino acids of the capsid region C9 to C29; MAb C-9 binds to a domain bounded by C64 and C97; MAbs E2-1 through E2-6 bind to the E2 glycoprotein backbone region from E2(1) to E2(115); MAbs E1-18 and E1-20 bind to the E1 glycoprotein region from E1(202) to E1(283). MAb E1-18 neutralizes RV infectivity; MAb E1-20 neutralizes infectivity and modestly inhibits hemagglutination. Analyses with selected synthetic peptides have confirmed several of the molecular domains deduced with the expressed proteins. These plasmid constructions and peptides have proven useful in beginning to unravel the molecular organization of several antigenic sites of this human pathogen.
Living with support.
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