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Modelling lymphocytic leukaemia incidence in England and Wales using generalizations of the two-mutation model of carcinogenesis of Moolgavkar, Venzon and Knudson.

Generalizations of the two-mutation carcinogenesis model of Moolgavkar, Venzon and Knudson (MVK) are fitted to England and Wales lymphocytic leukaemia incidence data covering the period 1971-1988. Both acute lymphocytic leukaemia (ALL) and chronic lymphocytic leukaemia (CLL) can be fitted by a model with two mutations. These two-mutation models are such that the first (but not the second) mutation rate and the susceptible stem cell population vary rapidly with age. CLL is also adequately fitted by a model with three mutations, and the mutation rates and the variation in the stem cell population numbers implied by the three-mutation model are more plausible than those of the two-mutation model. For CLL there are no significant differences between the sexes in either of the optimal models fitted, but this is not the case for ALL. Thus the original MVK model adequately describes population rates of lymphocytic leukaemia in England and Wales.

Adolescent↗

Socioeconomic inequalities in cancer survival in England and Wales.

BACKGROUND: Cancer survival often has been reported as lower for the poor than the rich, but, to the authors' knowledge, systematic national estimates of deprivation gradients in survival over long periods of time have not been available. METHODS: The authors estimated national population-based survival rates for almost 3 million people who were diagnosed with 1 of 58 types of cancers (47 in adults, 11 in children) in England and Wales during the 20-year period 1971-1990 and followed through December 31, 1995. Cancer patients were assigned by their address at diagnosis to 1 of 5 categories (quintiles of the national distribution) of material deprivation by using a standard index derived from census data on unemployment, car ownership, household overcrowding, and social class that was available for all 109,000 census tracts in Great Britain. The authors used relative survival rates: the ratio of observed survival among the cancer patients to the survival that would have been expected if they had had the same background mortality as the general population. Background mortality differed widely among socioeconomic categories, and the authors constructed life tables from raw national mortality data by gender, single year of age, calendar period of death, and socioeconomic category to adjust for it. The authors used variance-weighted least squares regression to estimate both time trends in age standardized survival and socioeconomic gradients in survival. The number of avoidable deaths was estimated from the observed mortality excess compared with the expected mortality in each group of patients. RESULTS: Survival rose steadily for most cancers over 25 years to 1995 in England and Wales, but inequalities in survival between patients living in rich and poor areas were geographically widespread and persistent over this period of time. These patterns existed for 44 of 47 adult cancers examined but not for 11 childhood cancers. These inequalities in survival represented more than 2500 deaths that would have been avoided each year if all cancer patients had had the same chance of surviving up to 5 years after diagnosis as patients in the most affluent group. CONCLUSIONS: The largest national cancer survival study has provided strong evidence of systematic disadvantage in outcome among patients who lived in poorer districts compared with those who lived in wealthier districts.

Adolescent↗

Resting metabolic rate in a sample of girls in Malaysia and England.

This cross-sectional study of age matched (10-11 years), pre-menarcheal girls in England and Malaysia investigated the effect of ethnicity on resting metabolic rate (RMR). The children were recruited from schools in Oxford, England, and Kuala Lumpur, Malaysia, and all measurements were conducted in the schools. The Malaysian girls were shorter (143.7 +/- 6.5 cm and 140.1 +/- 5.3 cm (mean +/- SD) for the English and Malaysian girls respectively) and lighter (32.5 +/- 5.3 kg compared with 38.0 +/- 8.7 kg for the English girls) with a smaller fat mass and fat free mass (FFM) than the English girls. Energy expenditure was lower in the Malaysian girls (4555 +/- 531 kJ/day compared with 5178 +/- 688 kJ/day for the English girls). Although a difference in RMR was observed between the two groups, when corrected for body composition the difference was no longer significant. No effect of ethnicity on the relationship of FFM and RMR was shown when the data were analyzed using analysis of covariance.

Body Composition↗

Tay-Sachs disease in persons of French-Canadian heritage in northern New England.

This study sought to determine whether persons of French-Canadian heritage in northern New England are at high risk for the lethal infantile form of Tay-Sachs disease. In order to accomplish this, death records and laboratory diagnostic records were surveyed to ascertain Tay-Sachs deaths in a cohort of 372,000 live births between 1977-1986. The proportion of the total population with French-Canadian or Jewish heritage was determined from census and birth records, and the ethnic background of Tay-Sachs cases was determined from the corresponding birth records. In 1,860 births, both parents were of Ashkenazi Jewish heritage. One of those children was diagnosed with Tay-Sachs disease. In 41,000 births, both parents were of French-Canadian heritage, and in an additional 93,000 births, one parent was of French-Canadian heritage. No cases of Tay-Sachs disease were identified in the offspring of those individuals. Approximately 14 cases (95% confidence interval 8-20) would be expected, if the gene frequency approximated that reported for individuals of Ashkenazi Jewish heritage. Based on the results of this study, routine testing for Tay-Sachs disease heterozygosity is not indicated for persons of French-Canadian heritage in northern New England. This conclusion may not necessarily be valid for persons of French-Canadian heritage residing in other states. Further studies of Tay-Sachs disease mutations and prevalence among persons of French-Canadian heritage will be important to determine possible regional variations in gene frequencies.

Child↗

Maxillary sinusitis in Medieval Chichester, England.

Maxillary sinusitis is a common medical complaint, affecting more than 30 million people per year in the United States alone. Very little palaeopathological work on this disease has been carried out, probably because of the enclosed nature of the sinuses in intact skulls and the lack of a suitable method for examination. This study tested the hypothesis that maxillary sinusitis was more common in people with leprosy than in people without it in Medieval England. The prevalence of maxillary sinusitis by age and sex was recorded in 133 individuals, some diagnosed as being leprous, derived from a later Medieval (12th to 17th centuries AD) urban hospital population at Chichester, Sussex, England using both macroscopic and endoscopic methods of examination. Of the 133 individuals with one or both sinuses available for examination, 54.9% (73) had evidence of bone change within the sinuses. There was no difference in prevalence between those with leprosy and those without, although clinical studies suggest that over 50% of lepromatous leprous individuals may develop sinusitis. Comparison with another study on Medieval British sites with a 3.6% prevalence (3 of 83) indicates that the prevalence at Chichester is much greater. The problems with diagnosing sinusitis are addressed and reasons behind the high frequency in this study are discussed. Aetiological factors predisposing to maxillary sinusitis are considered with reference to possible environmental conditions prevailing in the later Medieval period in Britain.

Bone and Bones↗

Skeletal manifestations of rickets in infants and young children in a historic population from England.

Gross and radiographic changes characteristic of inadequate bone mineralization due to rickets are described in 21 immature skeletons from a 19th century urban population from Birmingham, England. The aims of the study are as follows: to evaluate and if possible augment existing dry-bone criteria for the recognition of rickets in immature skeletal remains; to investigate the value of radiography for the paleopathological diagnosis of rickets; and to compare and contrast the expression of rickets in this group with that previously documented for a rural agrarian population from Wharram Percy, England. Some gross skeletal signs of rickets which were not previously well-documented in paleopathological studies are noted. The worth of radiography for evaluating structural changes to both cortical and trabecular bone in the disease is demonstrated, and features useful for the interpretation of vitamin D deficiency are discussed. The pattern of skeletal elements affected and the severity of changes differs in the Birmingham group from that seen in the comparative rural population. It is emphasized that a variety of factors may influence the expression of rickets in paleopathological material, including rate of skeletal growth, age cohort affected, and intensity of vitamin D deficiency. Nevertheless, careful analysis, not only of the frequency of rickets but also of the degree of severity of lesions and the patterning with respect to skeletal elements affected, may enable more nuanced understanding of the biocultural context of the disease in earlier populations.

Bone and Bones↗

Histological identification of syphilis in pre-Columbian England.

Microscopic analyses served to complement the macroscopic identification of venereal syphilis in two of four pre-Columbian skeletons from the site Hull Magistrates Court in England. Diagnosis was based on parameters presented by Schultz ([1994] Origin of Syphilis in Europe, Toulon: Centre Archaeologique du Var, p. 63-67; [2001] Yrbk. Phys. Anthropol. 44:106-147; [2003] Identification of Pathological Conditions in Human Remains, New York: Academic Press, p. 73-109), which characterized venereal syphilis at a histological level. Observation of the microarchitecture of these samples allowed a more comprehensive approach to identification of the disease (processes). In most samples, Polsters and Grenzstreifen (or remnants of such structures) could be identified, suggesting the presence of a chronic, inflammatory disease such as venereal syphilis. Sinous lacunae were also observed in all histological samples, pointing to lytic activity (osteitis). The combination of both proliferative and destructive processes is pathognomonic for syphilis, and histological analyses provided a more accurate diagnosis of this infectious disease in these four individuals. As a result, the histological evidence suggests that venereal syphilis was present in England prior to 1492. This secondary form of evidence supports the macroscopic identification of the disease, and shows the power of a multimethodological approach to paleopathological diagnoses.

Bone and Bones↗

The Oral Microbiome of King Richard III of England.

OBJECTIVES: Metagenomic investigations of ancient dental calculus provide insights into oral health, disease, and diet. Here, we analyze the dental calculus metagenome of King Richard III of England (1452-1485). MATERIALS AND METHODS: Dental calculus DNA was extracted from three teeth of King Richard III and shotgun sequenced to a depth of nearly 400 million reads. The metagenomic data were taxonomically profiled and compared to new and previously published dental calculus metagenomes from England, Ireland, the Netherlands, and Germany spanning the Neolithic to the present. Sequencing data were de novo assembled, and metagenome-assembled genomes assigned to the genus Tannerella were investigated for phylogenetic relatedness and virulence. Putative dietary DNA was assessed for authenticity. RESULTS: The dental calculus of King Richard III was well-preserved and yielded an exceptionally high quantity of DNA. Oral microbiome species diversity fell within the range previously observed among other northern European populations, suggesting that a royal lifestyle and a rich diet did not substantially impact his oral microbiota. The reconstructed Tannerella genomes contained many virulence factors found today among oral Tannerella species. No putative dietary DNA could be authenticated. DISCUSSION: The dental calculus of King Richard III produced one of the richest ancient oral metagenomes published to date, yet the species diversity was indistinguishable from that of commoners living in northern Europe over the last 7000 years. Insufficient plant and animal DNA were recovered to investigate diet, suggesting that dental calculus may not be a sufficient source of dietary DNA even when exceptionally well-preserved.

Humans↗

Policy, organisation and practice of specialist old age psychiatry in England.

OBJECTIVE: To describe and compare service arrangements in old age psychiatry across England according to three broad domains: (i) levels of professional autonomy; (ii) degree of community orientation (delivery of and links with community services) and (iii) degree of integration between health and social care provision. DESIGN: Cross sectional survey of consultants in old age psychiatry in England. Potential respondents were sourced from the Royal College of Psychiatrists and Regional Advisers in Old Age Psychiatry. MEASURES: A self-administered postal questionnaire was piloted and refined. The questionnaire domains listed above reflect core policy issues for older people's services, covering the domains above. RESULTS: There is marked variation in the deployment and use of professional staff in old age psychiatry, ranging from open access to multidisciplinary assessment to services only accessible by clinician referral. Patterns of linkage with primary care are likewise variable with only half of services providing the types of support recommended by the Audit Commission (2000). Community orientation was evident to a considerable extent in support to care homes and assessment practices. Links between health and social care appeared strongest in terms of liaison and training. There was less evidence of more formal integration through shared management of staff or for links with intensive home support for those with dementia. CONCLUSIONS: The data provide a unique picture and benchmark of the configuration of old age psychiatry, a core element of mental health care in old age, after some 25 years of development in the UK. There appears to be substantial variation on all three domains of comparison.

Aged↗

Does integration really make a difference? A comparison of old age psychiatry services in England and Northern Ireland.

OBJECTIVE: This paper seeks to address whether integrated structures are associated with more integrated forms of service. Northern Ireland has one of the most structurally integrated and comprehensive models of health and personal social services in Europe. Social and health services are jointly administered and this arrangement should, in theory, promote collaborative working and interdisciplinary arrangements. DESIGN: The study employed a cross-sectional survey of consultants in old age psychiatry in England and Northern Ireland. Potential respondents were sourced from the UK Royal College of Psychiatrists membership list and locally collected information. MEASURES: A self-administered postal questionnaire. Along with general service arrangements, the domains measured reflect core policy issues for older people's services. Under particular scrutiny in this study were the degree of integration of health and social service provision, as well as inter-professional team working. RESULTS: The integrated health and social care services in Northern Ireland do appear to provide more integrated patterns of working, primarily in managerial arrangements and in the location of staff. There was no evidence of the impact of integration on practice in areas such as: assessment, referral and medical screening. The factors found to be associated with greater integration of health and social care in the prediction model fell into three categories: provision of specialist services; provision of outreach activities; and shared policies by which the whole team worked. CONCLUSIONS: Health and personal social services in Northern Ireland have a distinct advantage over their counterparts in comparable areas of England. The results indicate that integrated structures in old age psychiatry services are associated more with integrated management systems and less with integrated practice-related activities. Further research is required on the effectiveness and cost effectiveness of integrating services in general. It is important that future intervention studies systematically measure the component parts, nature and extent of integration and their individual and joint contribution to the effectiveness and efficacy of services.

Aged↗

Sero-epidemiological patterns of Epstein-Barr and herpes simplex (HSV-1 and HSV-2) viruses in England and Wales.

The aim was to carry out a population-based sero-prevalence survey of Epstein-Barr virus (EBV) across a wide age range in England and Wales and to identify any associations between EBV and herpes simplex virus types one and two (HSV-1 and 2). Sera from an age-stratified sample of 2,893 individuals, submitted for diagnostic purposes to 15 public health laboratories in England and Wales in 1994, were tested for immunoglobulin G (IgG) antibody to EBV. The samples had been tested previously for IgG antibody to HSV-1 and HSV-2. The serological profile of EBV was consistent with an endemic infection with peaks in transmission in those less than 5 years old and in young adults. An age adjusted analysis found a significant association between EBV and HSV-1 seropositivity that is most likely explained by similarities in their mode of transmission. The very low seroprevalence of HSV-2 in this sample complicated the comparisons of EBV and HSV-1 with HSV-2. Any associations were most likely explained by chance. Given the association between EBV and HSV-1, it is likely that recently documented epidemiological changes in HSV-1 also apply to EBV. Continuing surveillance of these herpes viruses is necessary as the predicted changes could have a significant public health impact, especially in the young adult population.

Adolescent↗

Seroprevalence of antibodies to human herpesviruses in England and Hong Kong.

The age-related prevalence of antibodies to herpesviruses was compared in England and Hong Kong. Altogether 327 sera from England and 266 sera from Hong Kong were tested for antibodies to herpes simplex virus (HSV), varicella-zoster virus (VZV), Epstein-Barr virus (EBV), cytomegalovirus (CMV), and human herpesvirus 6 (HHV-6). Herpesvirus infections were common in both countries but generally were acquired earlier and were more prevalent in Hong Kong. Over 90% of children in Hong Kong were infected with VZV, EBV, and HHV-6 by 8 years of age. HSV and CMV were the least prevalent childhood infections in both countries, although, 30-40% of babies in Hong Kong became infected during the first year of life. CMV infections were rare throughout childhood in the English cohort. Overcrowding and early attendance at kindergarten may aid more efficient and earlier transmission of herpesvirus in Hong Kong. The high prevalence of CMV in particular may have implications for the management of young pregnant women and organ transplant recipients in Hong Kong.

Adolescent↗

Cancer in adolescents and young adults aged 15-24 years: a report from the North of England young person's malignant disease registry, UK.

BACKGROUND: Descriptions of population-based data have rarely been published specifically for adolescents and young adults with cancer. PROCEDURE: Data on young adults (15-24 years) diagnosed with cancer in the North of England from 1968 to 1997 were obtained from the Northern Region Young Person's Malignant Disease Registry. Temporal changes in incidence and survival rates were investigated. RESULTS: There were 2,329 first cancers diagnosed over the study period (M:F 1.22:1). Overall age standardized incidence was 174 cases per million 15-24 years old, per year, 190 for males and 157 for females. The most common cancers in young adults were Hodgkin disease (19%), carcinomas (15%), central nervous system tumors (14%), germ cell tumors (13%), and leukemia (11%). Comparing incidence for 1968-1977 with 1988-1997 there were significant increases in the incidence of bone tumors (rate ratio 1.72, 95% CI 1.10-2.68), testicular tumors (rate ratio 1.64, 95% CI 1.16-2.32), thyroid cancer (rate ratio 2.63, 95% CI 1.37-5.02), and malignant melanoma (rate ratio 2.04, 95% CI 1.36-3.08). Survival rates improved significantly (P < 0.001) over the study period; 5-year survival rates over the three time periods 1968-1977, 1978-1987, 1988-1997 for all cancers were 45% (95% CI 41%-49%), 62% (95% CI 58%-65%), and 74% (95% CI 71%-77%) respectively. CONCLUSIONS: Survival rates improved and there were significant increases in incidence for specific cancers in young adults in the North of England. Further research is required to identify the reasons for changing incidence and to investigate the late effects of treatment among survivors.

Adolescent↗

Trends and influences on use of antidiabetic drugs in England, 1992-2003.

OBJECTIVE: To describe trends in prescribing for glycaemic control in diabetes mellitus in England, 1993-2003, and to examine the effects of new clinical evidence or national guidance on these. DESIGN: Observational study of prescribing adjusted for extrapolated changes in epidemiology of insulin and non-insulin treated diabetes. SETTING: Primary care in England, 1992-2003. DATA SOURCES: Three monthly prescribing data from the Prescription Pricing Authority. MAIN OUTCOME MEASURES: Defined daily doses/patient/quarter of oral hypoglycaemics and of insulin. RESULTS: There was an increase in the prevalence of both insulin treated (85%) and non-insulin treated (80%) diabetes. There were increases in all drug use, which were largely explained by this: for example, sulphonylurea use increased by 101% in total but only 11% after correction for change in prevalence and population; insulin use increased by 140% in total, but 33% after correction. Neither guidances from the National Institute of Clinical Excellence nor new clinical evidence had any discernible effect on this. An exception was metformin use, which increased by 495% in total, and by 277% after correction. This increase occurred mainly from early 1998 and seemed to coincide with the publication of evidence of the specific benefits of metformin. CONCLUSIONS: There has been a trend towards more aggressive treatment of diabetes. National guidance may have reinforced this but has not altered the trend. Specific evidence around metformin may have been very influential in increasing its use.

Diabetes Mellitus↗

Trends in primary care antibiotic prescribing in England 1994-1998.

PURPOSE: To investigate the changing decisions to prescribe antibiotics as manifest in the patterns of prescriptions dispensed in England, and to investigate antibiotic prescribing in different types of practice. METHODS: Antibiotic prescribing data and practice characteristics collected for every practice in England for the years 1994/5-1997/8. Morbidity data for common infections was also obtained from published sources. RESULTS: Antibiotic prescribing was related to practice characteristics, with high prescribing in deprived and single-handed practices in particular. There was a fall in antibiotic prescribing in all types of practice of practice over the period of the study. Morbidity data from other sources shows a fall in diagnosed morbidity from some infectious diseases over the same period. There were no differences in choice of antibiotic in different types of practice. CONCLUSIONS: The fall in antibiotic prescribing is universal across all kinds of practices and is possibly related to the fall in diagnoses. It is uncertain whether this reflects true morbidity.

Age Factors↗

An integrated assessment of long-term changes in the hydrology of three lowland rivers in eastern England.

The flow records of the Rivers Bure, Nar and Wensum in eastern England have been examined with the aim of identifying long-term changes in flow behaviour relating to variations in rainfall amount, land use, land drainage intensity and water resources use. In the study area, and since 1931, there is no evidence of long-term change in rainfall amount or distribution, on either an annual or seasonal basis. Despite changes in water resources use and catchment characteristics since the beginning of the century, such as the ending of water milling and increased land drainage and arable farming, rainfall-runoff modelling over the period 1964-1992 showed that the relationship between rainfall and runoff has remained essentially unchanged in the three study rivers. A catchment resource model used to 'naturalise' the historic flow records for the period 1971-1992 to account for the net effect of water supply abstractions and discharges revealed that mean river flows have been altered by surface water and groundwater abstractions, although the average losses to mean weekly flows due to net abstractions for all water uses was no greater than 3%. Greater losses occurred during drought periods as a result of increased consumptive use of water for spray irrigation and amounted to a maximum loss of 24% in the Nar catchment. In lowland areas such as eastern England that are prone to summer dry weather and periodic drought conditions, an integrated approach to river basin management, as advocated by the EU Framework Directive, is recommended for future management of surface and groundwater resources for public water supplies, river regulation purposes and industrial and agricultural demands.

Conservation of Natural Resources↗

Genetic variants of cytoplasmic malate dehydrogenase (MDH:EC:1.1.1.37) in populations in England and the Indian subcontinent. A new S-MDH variant.

A new variant malate dehydrogenase is described, designated S-MDHInd to indicate its discovery in the Indian subcontinent pending full comparison with all other variants. It occurred during a survey of the incidence of variant S-MDH phenotypes in 4149 subjects in north-east England and 1494 subjects from several populations in the Indian region. The variants previously thought to be restricted to the New Guinea region and to African populations occurred in three English subjects in northeast England. The incidence of variant S-MDH phenotypes in other populations is summarised.

Bangladesh↗

Hospital discharges for inflammatory bowel disease. Time trends from England and the United States.

The present study analyzes time trends of inflammatory bowel disease (IBD) in England-Wales and the United States based on nationwide hospitalization statistics. Because these statistics cover the total population of each country, they may give a more representative picture of the true trends than previous analyses concerning only one region or health center. The Hospital In-patient Enquiry was used to evaluate time trends in England-Wales from 1962 to 1985, data from the National Hospital Discharge Survey and the Commission on Professional Activities were used for trends in the United States from 1970 to 1987. A rise of Crohn's disease persisted unabated in the old age groups throughout the observation period. It was less marked in those aged under 35 and reached a plateau during the most recent decade. In ulcerative colitis, discharge rates increased in the older age groups, but remained constant or declined in the middle or younger age groups, respectively. Similar trends were observed in all three surveys. The hospitalization data confirm similar age-specific trends of mortality. The difference between younger and older age groups suggests that generations born 60-80 years ago have become more likely to be affected by IBD leading to hospitalization and mortality. As these high-risk generations grow older, there is a relative rise of hospitalization and mortality from IBD in these subjects.

Adult↗