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1.  Trace elements in water and congenital malformations of the central nervous system in South Wales. 
The concentrations of 20 trace elements were determined by atomic absorption spectrophotometry on representative samples of tap-water collected from 48 local authority areas in South Wales. The associations between twelve trace elements and central nervous system (CNS) malformation rates for the 48 areas were examined. Significant correlations for four trace elements were observed. Of these, Al was positively correlated while for the remaining three-Ca, Ba, and Cu-negative associations were found. Regression analysis of the data suggested that the relationships between Ba and Cu with CNS malformation rates were improtant than those of Al and Ca.
PMCID: PMC478936  PMID: 949571
2.  Acanthamoeba keratitis in England and Wales: incidence, outcome, and risk factors 
AUTHOR:e-mail address please Aim: To determine the incidence, regional variation in frequency, outcome, and risk factors for acanthamoeba keratitis (AK) in England and Wales.
Methods: AK cases presenting from 1 October 1997 to 30 September 1999 were identified by the British Ophthalmic Surveillance Unit active reporting system. Clinical and patient postal questionnaire data were analysed.
Results: 106 reported cases met study criteria. The annual incidence for the 2 years was 1.26 and 1.13 per million adults and, for contact lens (CL) wearers, 21.14 and 17.53 per million. There was marked regional variation in incidence (0 to 85.13 per million adult CL wearers), with CL wearers in the south having a ninefold increased risk of AK compared with those resident in the north (95% confidence limits: 2.2–38.9, p<0.0001), and a threefold increased risk with hard as opposed to soft domestic water (95% confidence limits: 1.73 to 6.58, p<0.001). Treatment and outcome data were similar to those previously reported. 93/106 (88%) patients were CL wearers. Among these, 46/77 (60%) were disinfecting irregularly, and 20/63 (32%) had been swimming in CLs. One step hydrogen peroxide and chlorine release soft CL (SCL) disinfection systems were significantly over-represented among the cases. Among SCL users, one or more previously established risk factors for AK were identified in 50/55 (91%) patients.
Conclusions: The incidence was considerably higher than most previous estimates, and was static. The geographical variation in incidence may be partly related to the increase in risk associated with hard water. The fact that water quality can have such an effect on the risk of AK suggests that many CL wearers must be letting tapwater come into contact with their lenses or storage cases. Improved education for CL wearers and practitioners about hygiene practice and the variable efficacy of contact lens systems could be expected to reduce the incidence of this disease.
PMCID: PMC1771120  PMID: 11973250
acanthamoeba; keratitis; England and Wales
3.  Comparison of central nervous system malformations in spontaneous absortions in Northern Ireland and south-east England. 
British Medical Journal  1979;1(6175):1395-1397.
A study of 1140 pregnancies ending in spontaneous abortion disclosed a central nervous system (CNS) malformation in 4.9% of all complete conceptuses. Life-table analysis suggested that the incidence of CNS malformations is 16/1000 at the beginning of the eighth week of gestation. It was also estimated that only one-fifth of these infants are born alive, 41% being aborted spontaneously and 38% stillborn. A hypothesis that differences in the incidence of CNS malformations result from area differences in the mortality rate of malformed embryos and fetuses was examined by comparing the findings in Northern Ireland, an area of high incidence, with those in south-east England, an area of low incidence. In Northern Ireland 4.6% of complete conceptuses had a CNS malformation compared with 3.0% in south-east England, but the difference was not statistically significant. There is no evidence that in Northern Ireland a lower mortality rate among malformed fetuses and embryos is responsible for the high incidence of malformation at birth. The geographical variation of CNS malformations in the United Kingdom still awaits explanation.
PMCID: PMC1598902  PMID: 445098
4.  Congenital anterior abdominal wall defects in England and Wales 1987-93: retrospective analysis of OPCS data. 
BMJ : British Medical Journal  1996;313(7062):903-906.
OBJECTIVES: Analysis of incidence and characteristics of congenital abdominal wall defects, with special reference to the differences between the incidence of gastroschisis and exomphalos (omphalocele). DESIGN: Retrospective analysis using data from the Office of Population Censuses and Surveys (recoded to differentiate exomphalos and gastroschisis) and the National Congenital Malformation Notification Scheme. SETTING: England and Wales, 1987 to 1993. RESULTS: 1043 congenital anterior abdominal wall defects were notified within the seven year study period. Of these, 539 were classified as gastroschisis, 448 as exomphalos, 19 as "prune belly syndrome," and 37 as "unclassified." Gastroschisis doubled in incidence from 0.65 in 1987 to 1.35 per 10,000 total births in 1991, with little further change; the incidence of exomphalos decreased from 1.13 to 0.77 per 10000 births. The overall incidence of notified congenital abdominal wall defects was 2.15 per 10000 total births. Gastroschisis was associated with a lower overall maternal age than exomphalos and with a significantly lower proportion of additional reported congenital malformations (5.0%) than in the cohort with exomphalos (27.4%) (odds ratio 0.14, 95% confidence interval 0.09 to 0.22; P < 0.001). The sex ratio of the two cohorts was the same. The incidence of gastroschisis and exomphalos was higher in the northern regions of England than in the south east of the country. CONCLUSIONS: The national congenital malformation notification system showed an increasing trend in the incidence of fetuses born with gastroschisis and a progressive decreasing incidence of exomphalos in England and Wales between 1987 and 1993. Although the reasons for this are likely to be multifactorial, a true differential change seems likely. The observed increase in incidence of gastroschisis relative to exomphalos and the differentiation in maternal age have implications for resource management within the NHS and warrant further epidemiological monitoring. Regional differences may be due to a dietary or environmental factor, which requires further study.
PMCID: PMC2352268  PMID: 8876090
5.  Primary scene responses by Helicopter Emergency Medical Services in New South Wales Australia 2008–2009 
Despite numerous studies evaluating the benefits of Helicopter Emergency Medical Services (HEMS) in primary scene responses, little information exists on the scope of HEMS activities in Australia. We describe HEMS primary scene responses with respect to the time taken, the distances travelled relative to the closest designated trauma hospital and the receiving hospital; as well as the clinical characteristics of patients attended.
Clinical service data were retrospectively obtained from three HEMS in New South Wales between July 2008 and June 2009. All available primary scene response data were extracted and examined. Geographic Information System (GIS) based network analysis was used to estimate hypothetical ground transport distances from the locality of each primary scene response to firstly the closest designated trauma hospital and secondly the receiving hospital. Predictors of bypassing the closest designated trauma hospital were analysed using logistic regression.
Analyses included 596 primary missions. Overall the HEMS had a median return trip time of 94min including a median of 9min for activation, 34min travelling to the scene, 30min on-scene and 25min transporting patients to the receiving hospital. 72% of missions were within 100km of the receiving hospital and 87% of missions were in areas classified as ‘major cities’ or ‘inner regional’. The majority of incidents attended by HEMS were trauma-related, with road trauma the predominant cause (44%). The majority of trauma patients (81%) had normal physiology at HEMS arrival (RTS = 7.84). We found 62% of missions bypassed the closest designated trauma hospital. Multivariate predictors of bypass included: age; presence of spinal or burns trauma; the level of the closest designated trauma hospital; the transporting HEMS.
Our results document the large distances travelled by HEMS in NSW, especially in rural areas. The high proportion of HEMS missions that bypass the closest designated trauma hospital is a seldom mentioned benefit of HEMS transport. These results along with the characteristics of patients attended and the time HEMS take to complete primary scene responses are useful in understanding the benefit HEMS provides and the services it replaces.
PMCID: PMC3507904  PMID: 23152963
Wounds and injury; Trauma systems; Helicopter Emergency Medical Services; Patient acuity; Cost; Reimbursement
6.  Mortality from cardiovascular disease among interregional migrants in England and Wales. 
BMJ : British Medical Journal  1995;310(6977):423-427.
OBJECTIVE--To investigate the extent to which geographical variations in mortality from ischaemic heart disease and stroke in Britain are influenced by factors in early life or in adulthood. DESIGN--Longitudinal study of migrants. SUBJECTS--1% sample of residents in England and Wales born before October 1939 and enumerated at the 1971 census (the Office of Population Censuses and Surveys' longitudinal study). MAIN OUTCOME MEASURE--18,221 deaths from ischaemic heart disease and 9899 deaths from stroke during 1971-88 were analysed by areas of residence in 1939 and 1971. These included 2928 deaths from ischaemic heart disease and 1608 deaths from stroke among individuals moving between 14 areas defined by the major conurbations and nine standard administrative regions of England and Wales. RESULTS--The southeast to northwest gradient in mortality from ischaemic heart disease was related significantly to both the 1939 area (chi 2 = 6.09, df = 1) and area in 1971 (chi 2 = 5.05, df = 1). Geographical variations in mortality from stroke were related significantly to the 1939 area (chi 2 = 4.09, df = 1) but the effect of area in 1971 was greater (chi 2 = 8.07, df = 1). The effect of 1971 area on mortality from stroke was largely due to a lower risk of death from stroke among individuals moving into Greater London compared with migrants to the rest of the South East region (chi 2 = 4.54, df = 1). CONCLUSIONS--Geographical variations in mortality from cardiovascular disease in Britain may be partly determined by genetic factors, environmental exposures, or lifestyle acquired early in life, but the risk of fatal ischaemic heart disease and stroke changes on migration between areas with differing mortality. The low risk of death from stroke associated with residence in Greater London is acquired by individuals who move there.
PMCID: PMC2548815  PMID: 7873946
7.  Geographical variation in the standardized years of potential life lost ratio (SYPLR) in women dying from malignancies of the breast in England and Wales. 
British Journal of Cancer  1997;75(7):1069-1074.
Geographical variation in the standardized years of potential life lost ratio (SYPLR) in women aged 20-74 dying from breast cancer has been mapped by local authority district in England and Wales and compared with the variation as described by the standardized mortality ratio (SMR). The geographical distribution of areas of low and high SMRs is similar to that observed some 15 years earlier, showing an increase from north to south. In contrast, the pattern of SYPLRs shows a less obvious trend. Years of life lost because of breast cancer mortality were particularly high in eight of the 401 county districts (SYPLR 1.22-1.48) and particularly low in nine (0.60-0.86). Mapping SYPLRs for breast cancer gives a different pattern from mapping SMRs, and one which is possibly more appropriate for targeting resources in circumstances in which death at younger age will have major social consequences. Care is required in interpreting maps indicating high and low rates in the presence of multiple comparisons. However, the range of values observed is suggestive of the need to investigate districts with contrasting values of SYPLR with respect to the inter-relationships between sociodemographic characteristics, duration of symptoms, clinical presentation and treatment efficacy.
PMCID: PMC2222757  PMID: 9083345
8.  Area Differences in Spontaneous Abortion Rates in South Wales and Their Relation to Neural Tube Defect Incidence 
British Medical Journal  1973;4(5883):20-22.
Data are presented from the South Wales Congenital Malformation Survey (92,982 births 1964-6 inclusive) showing that within areas in South Wales there exists an inverse relation between previous spontaneous abortion rate and the prevalence at birth of neural tube defect (anencephaly or spina bifida cystica or both). This relation is independent of social class, parity, and maternal age, and is not likely to be explained by area differences in accuracy of reporting previous spontaneous abortions.
On the basis of these findings a hypothesis is advanced which proposes that the incidence of neural tube defects is uniform throughout South Wales and that the present substantial and relatively stable differences in area prevalence are controlled by small area differences in mortality of malformed embryos. This would seem to suggest that factors initiating the malformation are genetic and that any related environmental factors exert their effect on already abnormal fetuses by influencing, in one way or another, their capacity to survive.
PMCID: PMC1587098  PMID: 4585417
9.  Population based study of late onset cerebellar ataxia in south east Wales 
Objective: To determine the prevalence and causation of late onset cerebellar ataxia (LOCA) in south east Wales, United Kingdom.
Methods: A population based study of LOCA was conducted in a defined geographical region with a total population of 742 400. Multiple sources of ascertainment were used to identify all cases prevalent on 1 January 2001. The inclusion criteria were: a predominantly progressive cerebellar ataxia with onset of symptoms at age ⩾18 years; and disease duration of ⩾1 year. Cases with known acquired ataxias, ataxic syndromes with associated prominent autonomic dysfunction and/or atypical parkinsonism suggestive of multiple system atrophy and disorders with ataxia as a minor feature were excluded.
Results: We identified 76 index cases of LOCA, of whom 63 were sporadic, idiopathic LOCA (ILOCA) and 13 were familial LOCA, of whom six had either spinocerebellar ataxia type 6, Friedreich's ataxia or dominant episodic ataxia. The mean annual incidence rate for the period 1999–2001 was 0.3/100 000 population/year. The crude prevalence rates were 8.4 per 100 000 (95% CI 7.2 to 11.6) for ILOCA and 1.8 per 100 000 (95% CI 0.8 to 2.7) for inherited LOCA. Of the 54/63 (85.7%) patients with ILOCA who were assessed, mean (SD) age at onset of symptoms was 53.8 (14.1) years (range 19 to 78) with a male:female ratio of 2.1:1. The mean disease duration was 8.7 (6.3) years (range 1 to 31). The most frequent presenting complaint was disturbance in gait (90.7%). One-third had a relatively pure cerebellar syndrome (33.3%) and two-thirds (66.7%) had additional extracerebellar neurological features. The majority (92%) were ambulant but only 9.3% were independently self-caring.
Conclusion: This population based study provides insight into LOCA within a defined region and will inform decisions about the rational use of healthcare resources for patients with LOCA.
PMCID: PMC1739172  PMID: 15258214
10.  Dental caries in 14- and 15-year-olds in New South Wales, Australia 
BMC Public Health  2013;13:1060.
Dental caries remains one of the most common chronic diseases of adolescents. In Australia there have been few epidemiological studies of the caries experience of adolescents with most surveys focusing on children. The New South Wales (NSW) Teen Dental Survey 2010 is the second major survey undertaken by the Centre for Oral Health Strategy. The survey is part of a more systematic and efficient approach to support State and Local Health District dental service planning and will also be used for National reporting purposes.
Data for the NSW Teen Dental Survey were collected in 2010 from a random sample of Year 9 secondary school students aged 14 to 15 years from metropolitan and non-metropolitan schools under the jurisdiction of the NSW Department of Education and Training, the Catholic Education Commission and Independent Schools in New South Wales. Nineteen calibrated examiners performed 1269 clinical examinations at a total of 84 secondary schools across NSW. The survey was accompanied by a questionnaire looking at oral health related behaviours, risk factors and the usage of the Medicare Teen Dental Plan.
175 schools were contacted, with 84 (48%) accepting the invitation to participate in the study. A total of 5,357 student consent forms and parent information packages were sent out and 1,256 students were examined; leading to a student participation rate of 23%. The survey reported a mean DMFT for 14 and 15 year olds of 1.2 and it was identified that 45.4% of students had an experience of dental caries. Major variations in caries experience reported occurred by remoteness, water fluoridation status, socio-economic status and household income levels.
The NSW Teen Dental Survey provided state-wide data that will contribute to the national picture on adolescent oral health. The mean DMFT score of 1.2 is similar to the national caries experience data for this age group from the Australian Child Dental Health Survey in 2009.
PMCID: PMC3840655  PMID: 24209635
Teen dental survey; School children; Adolescents; Caries experience
11.  An objective index of walkability for research and planning in the Sydney Metropolitan Region of New South Wales, Australia: an ecological study 
Walkability describes the capacity of the built environment to support walking for various purposes. This paper describes the construction and validation of two objective walkability indexes for Sydney, Australia.
Walkability indexes using residential density, intersection density, land use mix, with and without retail floor area ratio were calculated for 5,858 Sydney Census Collection Districts in a geographical information system. Associations between variables were evaluated using Spearman’s rho (ρ). Internal consistency and factor structure of indexes were estimated with Cronbach’s alpha and principal components analysis; convergent and predictive validity were measured using weighted kappa (κw) and by comparison with reported walking to work at the 2006 Australian Census using logistic regression. Spatial variation in walkability was assessed using choropleth maps and Moran’s I.
A three-attribute abridged Sydney Walkability Index comprising residential density, intersection density and land use mix was constructed for all Sydney as retail floor area was only available for 5.3% of Census Collection Districts. A four-attribute full index including retail floor area ratio was calculated for 263 Census Collection Districts in the Sydney Central Business District. Abridged and full walkability index scores for these 263 areas were strongly correlated (ρ=0.93) and there was good agreement between walkability quartiles (κw=0.73). Internal consistency ranged from 0.60 to 0.71, and all index variables loaded highly on a single factor. The percentage of employed persons who walked to work increased with increasing walkability: 3.0% in low income-low walkability areas versus 7.9% in low income-high walkability areas; and 2.1% in high income-low walkability areas versus 11% in high income-high walkability areas. The adjusted odds of walking to work were 1.05 (0.96–1.15), 1.58 (1.45–1.71) and 3.02 (2.76–3.30) times higher in medium, high and very high compared to low walkability areas. Associations were similar for full and abridged indexes.
The abridged Sydney Walkability Index has predictive validity for utilitarian walking, will inform urban planning in Sydney, and will be used as an objective measure of neighbourhood walkability in a large population cohort. Abridged walkability indexes may be useful in settings where retail floor area data are unavailable.
PMCID: PMC3877990  PMID: 24365133
12.  Disease Presentation in Relation to Infection Foci for Non-Pregnancy-Associated Human Listeriosis in England and Wales, 2001 to 2007▿  
Journal of Clinical Microbiology  2009;47(10):3301-3307.
Listeriosis is a rare but severe food-borne disease, affecting unborn or newly delivered infants, the elderly, and the immunocompromised. The epidemiology of listeriosis in England and Wales changed between 2001 and 2007, with more patients ≥60 years old presenting with bacteremia (but without central nervous system [CNS] involvement). In order to explain this increase and understand the altered disease presentation, clinical, microbiological, and seasonal data on bacteremic cases of Listeria monocytogenes infection identified through national surveillance were compared with those for patients with CNS infections. Logistic regression analysis was applied while controlling for age. Bacteremic patients, who presented more frequently with gastrointestinal symptoms, were more likely to have underlying medical conditions than CNS patients. This was most marked in patients with malignancies, particularly digestive organ malignancies. Treatment to reduce stomach acid secretion modified the effect of nonmalignant underlying conditions on outcome, i.e., patients with an underlying condition who were not taking acid-suppressing medication were equally likely to have a bacteremic or a CNS infection. However, this type of therapy did not modify the effect of malignancies on the likelihood of having a bacteremic or a CNS infection. The increase in the incidence of human listeriosis among patients ≥60 years old in England and Wales between 2001 and 2007 appears to have occurred in those with cancer or other conditions whose treatment included acid-suppressing medication. Therefore, this vulnerable patient group needs specific dietary advice on avoiding risk factors for listeriosis.
PMCID: PMC2756898  PMID: 19675217
13.  Incidence of leukaemia and lymphoma in young people in the vicinity of the petrochemical plant at Baglan Bay, South Wales, 1974 to 1991. 
OBJECTIVE--To determine whether there was an increased incidence of leukaemias and lymphomas in young people aged less than 25 years in the locality of a petrochemical plant at Baglan Bay, South Wales. METHODS--Geographical population based study to compare the observed and expected incidence of leukaemia and lymphoma with onset before the age of 25, in the years 1974 to 1991. The population was aged 0-24 years and lived within 1.5 and 3 km of the plant. The observed number of cases in various categories were compared with the expected numbers of cases calculated from the Welsh cancer registration rates. RESULTS--Although the observed numbers were generally greater than would be expected, none of the comparisons showed significant excess of leukaemias or lymphomas for any period of years. CONCLUSIONS--The study shows that the incidence of leukaemias and lymphomas in children and young people in the area around the BP Chemical site at Baglan Bay, South Wales, between the years 1974 and 1991 was not significantly greater than normal.
PMCID: PMC1128199  PMID: 7795736
14.  Mortality from congenital malformations in England and Wales: variations by mother's country of birth. 
Archives of Disease in Childhood  1989;64(10):1457-1462.
Stillbirth and infant mortality from congenital malformations in England and Wales during 1981-5 was investigated according to the mother's country of birth. Significant differences remained after standardising for maternal age and social class. The highest overall mortality was in infants of mothers born in Pakistan (standardised mortality ratio 237), followed by infants of mothers born in India (standardised mortality ratio 134), East Africa (standardised mortality ratio 126), and Bangladesh (standardised mortality ratio 118). Caribbean and West African mothers showed an overall deficit. Mortality was inversely related to social class in all groups except the Afro-Caribbean. Infants of mothers born in Pakistan had the highest mortality in every social class except I, and for most anomalies investigated. Their ratios were particularly high for limb and musculoskeletal anomalies (standardised mortality ratio 362), genitourinary anomalies (standardised mortality ratio 268), and central nervous system anomalies (standardised mortality ratio 239). Our findings highlight the need for further research to identify the causes underlying these differences.
PMCID: PMC1792797  PMID: 2817931
15.  Empirical determinants of measles metapopulation dynamics in England and Wales. 
A key issue in metapopulation dynamics is the relative impact of internal patch dynamics and coupling between patches. This problem can be addressed by analysing large spatiotemporal data sets, recording the local and global dynamics of metapopulations. In this paper, we analyse the dynamics of measles meta-populations in a large spatiotemporal case notification data set, collected during the pre-vaccination era in England and Wales. Specifically, we use generalized linear statistical models to quantify the relative importance of local influences (birth rate and population size) and regional coupling on local epidemic dynamics. Apart from the proportional effect of local population size on case totals, the models indicate patterns of local and regional dynamic influences which depend on the current state of epidemics. Birth rate and geographic coupling are not associated with the size of major epidemics. By contrast, minor epidemics--and especially the incidence of local extinction of infection--are influenced both by birth rate and geographical coupling. Birth rate at a lag of four years provides the best fit, reflecting the delayed recruitment of susceptibles to school cohorts. A hierarchical index of spatial coupling to large centres provides the best spatial model. The model also indicates that minor epidemics and extinction patterns are more strongly influenced by this regional effect than the local impact of birth rate.
PMCID: PMC1688869  PMID: 9493407
16.  Cancer incidence in migrants to New South Wales from England, Wales, Scotland and Ireland. 
British Journal of Cancer  1990;62(6):992-995.
Cancer incidence in migrants to New South Wales (NSW) from individual countries within the British Isles has been compared with that in the Australian-born population using data from the NSW Central Cancer Registry for the period 1972-84. Indirectly age-standardised incidence ratios (SIR) showed that, for cancer at all sites combined, Scottish migrants had a significantly higher, and English migrants a lower, incidence than the native-born Australians. Melanoma of skin was less common in migrants from all four countries while lung cancer was more common. In all except the Irish migrants, stomach cancer was more frequent than in the Australian-born. Raised SIRs for bladder cancer were found in men from all the countries and for breast cancer in all except the Irish women but only in the English migrants were these ratios significant. English migrants differed from those from Wales, Scotland and Ireland in that, compared with the Australian-born, they had significantly lower SIRs for cancer of the colon (both sexes), head and neck, larynx and prostate (men), gallbladder and kidney (women), and a higher SIR for ovarian cancer. Bone cancer was relatively more common in men born in Wales. 'Other genital' cancers (penis and scrotum; vulva and vagina) tended to be more frequent in migrants from each country than in the Australian-born.
PMCID: PMC1971585  PMID: 2257232
17.  Multiple sclerosis distribution in England and Wales and parts of Europe 
The Journal of Hygiene  1971;69(3):373-389.
Scotland and Ireland have the highest death rates from multiple sclerosis and high rates are recorded in an area extending south-eastward from Britain through central Europe. The rates tend to diminish with rising latitude and longitude. In England and Wales the county boroughs with notably high rates during 1958-67 were mostly textile towns with cotton and wool mills, situated in the area recording the lowest average levels of sunshine. In the London area mortality from multiple sclerosis was high in those western boroughs and adjacent counties most exposed to the noise of aircraft using the airports of London. The geographical pattern in England suggests that noise and vibration of particular kinds may be a factor in causation along with a climatic factor, but this hypothesis is speculative until further evidence is found to support it.
PMCID: PMC2130897  PMID: 5285941
18.  Environmental and State-Level Regulatory Factors Affect the Incidence of Autism and Intellectual Disability 
PLoS Computational Biology  2014;10(3):e1003518.
Many factors affect the risks for neurodevelopmental maladies such as autism spectrum disorders (ASD) and intellectual disability (ID). To compare environmental, phenotypic, socioeconomic and state-policy factors in a unified geospatial framework, we analyzed the spatial incidence patterns of ASD and ID using an insurance claims dataset covering nearly one third of the US population. Following epidemiologic evidence, we used the rate of congenital malformations of the reproductive system as a surrogate for environmental exposure of parents to unmeasured developmental risk factors, including toxins. Adjusted for gender, ethnic, socioeconomic, and geopolitical factors, the ASD incidence rates were strongly linked to population-normalized rates of congenital malformations of the reproductive system in males (an increase in ASD incidence by 283% for every percent increase in incidence of malformations, 95% CI: [91%, 576%], p<6×10−5). Such congenital malformations were barely significant for ID (94% increase, 95% CI: [1%, 250%], p = 0.0384). Other congenital malformations in males (excluding those affecting the reproductive system) appeared to significantly affect both phenotypes: 31.8% ASD rate increase (CI: [12%, 52%], p<6×10−5), and 43% ID rate increase (CI: [23%, 67%], p<6×10−5). Furthermore, the state-mandated rigor of diagnosis of ASD by a pediatrician or clinician for consideration in the special education system was predictive of a considerable decrease in ASD and ID incidence rates (98.6%, CI: [28%, 99.99%], p = 0.02475 and 99% CI: [68%, 99.99%], p = 0.00637 respectively). Thus, the observed spatial variability of both ID and ASD rates is associated with environmental and state-level regulatory factors; the magnitude of influence of compound environmental predictors was approximately three times greater than that of state-level incentives. The estimated county-level random effects exhibited marked spatial clustering, strongly indicating existence of as yet unidentified localized factors driving apparent disease incidence. Finally, we found that the rates of ASD and ID at the county level were weakly but significantly correlated (Pearson product-moment correlation 0.0589, p = 0.00101), while for females the correlation was much stronger (0.197, p<2.26×10−16).
Author Summary
Disease clusters are defined as geographically compact areas where a particular disease, such as a cancer, shows a significantly increased rate. It is presently unclear how common such clusters are for neurodevelopmental maladies, such as autism spectrum disorders (ASD) and intellectual disability (ID). In this study, examining data for one third of the whole US population, the authors show that (1) ASD and ID display strong clustering across US counties; (2) counties with high ASD rates also appear to have high ID rates, and (3) the spatial variation of both phenotypes appears to be driven by environmental, and, to a lesser extent, economic incentives at the state level.
PMCID: PMC3952819  PMID: 24625521
19.  Predicting cardiovascular risk in England and Wales: prospective derivation and validation of QRISK2 
BMJ : British Medical Journal  2008;336(7659):1475-1482.
Objective To develop and validate version two of the QRISK cardiovascular disease risk algorithm (QRISK2) to provide accurate estimates of cardiovascular risk in patients from different ethnic groups in England and Wales and to compare its performance with the modified version of Framingham score recommended by the National Institute for Health and Clinical Excellence (NICE).
Design Prospective open cohort study with routinely collected data from general practice, 1 January 1993 to 31 March 2008.
Setting 531 practices in England and Wales contributing to the national QRESEARCH database.
Participants 2.3 million patients aged 35-74 (over 16 million person years) with 140 000 cardiovascular events. Overall population (derivation and validation cohorts) comprised 2.22 million people who were white or whose ethnic group was not recorded, 22 013 south Asian, 11 595 black African, 10 402 black Caribbean, and 19 792 from Chinese or other Asian or other ethnic groups.
Main outcome measures First (incident) diagnosis of cardiovascular disease (coronary heart disease, stroke, and transient ischaemic attack) recorded in general practice records or linked Office for National Statistics death certificates. Risk factors included self assigned ethnicity, age, sex, smoking status, systolic blood pressure, ratio of total serum cholesterol:high density lipoprotein cholesterol, body mass index, family history of coronary heart disease in first degree relative under 60 years, Townsend deprivation score, treated hypertension, type 2 diabetes, renal disease, atrial fibrillation, and rheumatoid arthritis.
Results The validation statistics indicated that QRISK2 had improved discrimination and calibration compared with the modified Framingham score. The QRISK2 algorithm explained 43% of the variation in women and 38% in men compared with 39% and 35%, respectively, by the modified Framingham score. Of the 112 156 patients classified as high risk (that is, ≥20% risk over 10 years) by the modified Framingham score, 46 094 (41.1%) would be reclassified at low risk with QRISK2. The 10 year observed risk among these reclassified patients was 16.6% (95% confidence interval 16.1% to 17.0%)—that is, below the 20% treatment threshold. Of the 78 024 patients classified at high risk on QRISK2, 11 962 (15.3%) would be reclassified at low risk by the modified Framingham score. The 10 year observed risk among these patients was 23.3% (22.2% to 24.4%)—that is, above the 20% threshold. In the validation cohort, the annual incidence rate of cardiovascular events among those with a QRISK2 score of ≥20% was 30.6 per 1000 person years (29.8 to 31.5) for women and 32.5 per 1000 person years (31.9 to 33.1) for men. The corresponding figures for the modified Framingham equation were 25.7 per 1000 person years (25.0 to 26.3) for women and 26.4 (26.0 to 26.8) for men). At the 20% threshold, the population identified by QRISK2 was at higher risk of a CV event than the population identified by the Framingham score.
Conclusions Incorporating ethnicity, deprivation, and other clinical conditions into the QRISK2 algorithm for risk of cardiovascular disease improves the accuracy of identification of those at high risk in a nationally representative population. At the 20% threshold, QRISK2 is likely to be a more efficient and equitable tool for treatment decisions for the primary prevention of cardiovascular disease. As the validation was performed in a similar population to the population from which the algorithm was derived, it potentially has a “home advantage.” Further validation in other populations is therefore advised.
PMCID: PMC2440904  PMID: 18573856
20.  Why is mortality higher in poorer areas and in more northern areas of England and Wales? 
STUDY OBJECTIVE: To identify and quantify the factors responsible for the differences in mortality between affluent and deprived areas, the north and the south, and urban and rural areas in England and Wales. DESIGN: A multiple Poisson regression analysis of cause specific mortality in the 403 local authority districts, each classified by deprivation (using the Jarman Index), latitude (from 50 degrees to 55 degrees north) and urbanisation, adjusting for age, sex, and proportion of ethnic minorities. SETTING: England and Wales 1992. MAIN RESULTS: All cause mortality was 15% higher in the districts comprising the most compared with the least deprived tenth of the population, 23% higher in the most northern (55 degrees) than in the most southern (50 degrees) districts, and 4% higher in metropolitan (within large cities) than rural districts. Nationally these differences were associated with 40,000, 65,000, and 15,000 excess deaths respectively. More than two thirds of the overall excess mortality with deprivation, latitude, and urbanisation was from three diseases--ischaemic heart disease, lung cancer, and chronic bronchitis and emphysema. The excess mortality from these and other diseases closely matched that predicted from differences according to deprivation and latitude in smoking, heavy alcohol consumption, Helicobacter pylori infection, and temperature, and thus could be attributed to these causes. About 85% of the overall excess mortality with deprivation was attributable to heavier smoking and 6% to heavier alcohol consumption, but diet varied little. Deaths more directly related to deprivation (such as those caused by H pylori infection, drug misuse, psychoses) accounted for an estimated 12% of the excess deaths, but variation in provision and uptake of healthcare services only 1%. The direct effects of deprivation are more strongly related to morbidity than mortality. Of the difference in mortality with latitude, about 45% was attributable to differences in smoking, and 25% to climate (mainly the association of cardiovascular and respiratory disease with cold). The differences with urbanisation were mainly because of smoking. CONCLUSIONS: Differences in the prevalence of smoking account for much of the variation in mortality between areas. Alcohol accounts for some, diet little. The more direct material effect of deprivation contributes to the variation in mortality but is particularly important with respect to differences in morbidity.
PMCID: PMC1756726  PMID: 9764254
21.  Seasonality of coronary artery deaths in New South Wales, Australia 
Heart  2002;88(1):30-34.
Background: Complex temporal variations in coronary deaths, including diurnal, weekly, and seasonal trends, have been reported worldwide.
Objective: To describe the magnitude of seasonal changes in coronary artery deaths in New South Wales, Australia.
Design: Hospital morbidity data, mortality statistics, and meteorological data were modelled using time series techniques to determine seasonality of coronary deaths. Data were also analysed to determine whether there was an increase in deaths before or after the Christmas and New Year holidays.
Results: A clear seasonality of coronary deaths was shown, with a peak in July. A mean of 2.8 excess coronary deaths per 100 deaths was estimated to occur from June to August each year, with a mean annual excess of 224 winter deaths a year. Mortality data did not show an increase in coronary death ratios before (p = 0.626) or after (p = 0.813) the Christmas and New Year holidays in December.
Conclusions: There is a higher incidence of coronary deaths in winter, which may reflect winter respiratory infections, the direct effect of cold, seasonal changes in lipid concentration, and other factors associated with winter. Hospitals should have contingency plans during the winter months to manage larger numbers of cardiac admissions.
PMCID: PMC1767180  PMID: 12067938
coronary artery disease; mortality; seasonality
22.  Variations in cancer mortality among local authority areas in England and Wales: relations with environmental factors and search for causes. 
Geographical variations in specific causes of mortality among the 1366 local authority areas of England and Wales as defined at 1971 were studied by examining extracts from death certificates held on computer tape. Five items of information on each death--year of death, age at death, sex, local authority area of residence, and the underlying cause of death, during the 11 years 1968-78--permitted a more detailed investigation than had been possible before. Analysis of some early results of the study--including maps of mortality for pleural mesothelioma, nasal cancer and bladder cancer--suggested that, despite the known limitations of death certification, systematic study of the mortality of small areas may give clues to aetiological factors in the environment. Analyses relating mortality to the distribution of environmental factors and examining disease profiles of each area may also provide clues. These will be followed up by other methods of study, such as case-control techniques.
PMCID: PMC1496383  PMID: 6802227
23.  Geographical mapping of type 1 diabetes in children and adolescents in south east Sweden 
Study objective: As earlier studies have shown space-time clusters at onset of type 1 diabetes in the south east region of Sweden we investigated if there also has been any geographical clusters of diabetes in this region.
Design: The place of residence (coordinates) at the time of diagnosis were geocoded in a geographical information system (GIS). All children diagnosed with type 1 diabetes up to 16 years of age at diagnosis between 1977–1995 were included. The population at risk was obtained directly from the population registry for the respective years and geographical area levels.
Setting: South east region of Sweden containing 5 counties, 49 municipalities, and 525 parishes.
Main results: A significant geographical variation in incidence rate were found between the municipalities (p<0.001) but not between the counties. The variation became somewhat weaker when excluding the six largest municipalities (p<0.02). In municipalities with increased risk (>35.1/100 000) the major contribution comes from children in age group 6–10 years of age at diagnosis. There were no obvious differences between the age groups in municipalities with decreased risk (<20.1/100 000). Boys and girls had about the same degree of geographical variation.
Conclusions: Apart from chance, the most probable explanation for the geographical variation in the risk for children and adolescents to develop type 1 diabetes between the municipalities in the region is that local environmental factors play a part in the process leading to the disease.
PMCID: PMC1732763  PMID: 15082736
24.  Ethnic variations in incidence of asthma episodes in England & Wales:national study of 502,482 patients in primary care 
Respiratory Research  2005;6(1):120.
Recent studies have demonstrated marked international variations in the prevalence of asthma, but less is known about ethnic variations in asthma epidemiology within individual countries and in particular the impact of migration on risk of developing asthma. Recent within country comparisons have however revealed that despite originating from areas of the world with a low risk for developing asthma, South Asian and Afro-Caribbean people in the UK are significantly (3× and 2× respectively) more likely to be admitted to hospital for asthma related problems than Whites.
Using data from the Fourth National Study of Morbidity Statistics in General Practice, a one-percent broadly representative prospective cohort study of consultations in general practice, we investigated ethnic variations in incident asthma consultations (defined as new or first consultations), and compared consultation rates between those born inside and outside the UK (migrant status). Logistic regression models were used to examine the combined effects of ethnicity and migration on asthma incident consultations.
Results showed significantly lower new/first asthma consultation rates for Whites than for each of the ethnic minority groups studied (mean age-adjusted consultation rates per 1000 patient-years: Whites 26.4 (95%CI 26.4, 26.4); South Asians 30.4 (95%CI 30.3, 30.5); Afro-Caribbeans 35.1 (95%CI 34.9, 35.3); and Others 27.8 (27.7, 28.0). Within each of these ethnic groups, those born outside of the UK showed consistently lower rates of incident asthma consultations. Modelling the combined effects of ethnic and migrant status revealed that UK-born South Asians and Afro-Caribbeans experienced comparable risks for incident GP consultations for asthma to UK-born Whites. Non-UK born Whites however experienced reduced risks (adjusted OR 0.82, 95%CI 0.69, 0.97) whilst non-UK born South Asians experienced increased risks (adjusted OR 1.33, 95%CI 1.04, 1.70) compared to UK-born Whites.
These findings strongly suggest that ethnicity and migration have significant and independent effects on asthma incidence. The known poorer asthma outcomes in UK South Asians and Afro-Caribbeans may in part be explained by the offspring of migrants experiencing an increased risk of developing asthma when compared to UK-born Whites. This is the first study to find heterogeneity for incident asthma consultations in Whites by migrant status.
PMCID: PMC1276818  PMID: 16242029
25.  Health service accessibility and deaths from asthma in 401 local authority districts in England and Wales, 1988-92 
Thorax  1997;52(3):218-222.
BACKGROUND: The possible contribution of health service accessibility to asthma mortality has not previously been studied in the UK. METHODS: Using regression analysis, the relationship between geographical isolation from large acute hospital services and mortality from asthma for 401 local authority districts in England and Wales was examined for the period 1988-92. RESULTS: Asthma mortality was found to be strongly associated with the proportion of district households where the head was of social class 4 or 5 (adjusted relative risk 1.61, 95% confidence interval (CI) 1.12 to 2.33), and the proportion of households without access to a car (adjusted relative risk 1.59, 95% CI 0.97 to 2.62). After controlling for these factors, there was a tendency for mortality to rise with increasing distance from hospital, with a relative risk of 1.01 for an increase in distance of one kilometre (95% CI 1.00 to 1.02). CONCLUSIONS: The findings suggest that problems of accessibility of care may mean that the control of asthma amongst sufferers living in districts most remote from major health service units might be less than optimal, and this could result in a number of potentially avoidable deaths. 

PMCID: PMC1758521  PMID: 9093335

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