Space-time clustering of acute lymphoblastic leukaemia in parts of the U.K. (1984-1993).

Age-related differences in the incidence and immunological subtypes of acute lymphoblastic leukaemia (ALL) suggest that it may be composed of more than one disease entity, each with different aetiologies. Childhood leukaemia (of which the majority of cases are ALL) has been suspected of having an infectious aetiology, but few studies have systematically examined ALL for clustering by age group. The aim of this study was to examine ALL for evidence of space-time clustering of date and place of diagnosis by age group. Knox space-time analysis was carried out separately for three different age groups: childhood (0-14 years), young adult (15-34 years) and older adults (35-79 years). Data on 968 cases of ALL aged 0-79 years, arising during 1984-1993 in the areas covered by a specialist population based register of leukaemias and lymphomas in parts of the U.K., were used in the analysis. Space-time clustering of diagnoses was limited to children aged 0-14 years. It was more prominent in those diagnosed in the period 1984-1988, than in those diagnosed in 1989-1993. The clustering may indicate an infectious aetiology for childhood ALL, or could be the result of episodic exposures to some environmental hazard.

Space-time clustering of Hodgkin's Disease in parts of the UK, 1984-1993.

The object of this study was to examine cases of Hodgkin's Disease (HD) for evidence of space-time clustering of onsets by age group, sex and disease subtype. Data comprised 2024 cases of HD aged 0-79 years arising throughout the period 1984 to 1993 in the areas covered by a specialist population based register of leukaemias and lymphomas. Knox space-time analysis was used separately for 3 different age groups: childhood (0-14 years), young adult (15-34 years) and older adults (35-79 years); for adult cases separate analysis was carried out by sex and for the nodular and non-nodular sclerosing subtypes. Results showed that space-time clustering of onsets was limited to the nodular sclerosing cases. It was more prominent in young adult nodular sclerosing cases aged 15-34 years (particularly females) diagnosed in the period 1984-88, than in those diagnosed in 1989-93. We conclude that clustering may provide further evidence that an infectious process is involved in the aetiology of young adult nodular sclerosing cases of HD.

Hazard proximities of childhood cancers in Great Britain from 1953-80.

STUDY OBJECTIVES: Firstly, to examine relationships between the birth and death addresses of children dying from leukaemia and cancer in Great Britain, and the sites of potential environmental hazards; and secondly to measure relative case densities close to, and at increasing distances from, different hazard types. DESIGN: Home address postcodes (PCs) and their map coordinates were identified at birth and at death in children who died from leukaemia or cancer. Potentially hazardous industrial addresses and PCs were listed from business and other directories, and map coordinates obtained from the Central Postcode Directory or else located directly on Ordnance Survey (OS) maps. Railway lines and motorways were digitised from OS maps. Numbers of deaths (and births) at successive radial distances from these hazards were counted and compared with expected numbers. The latter were based on a count of all PCs at similar distances. Relative case density ratios at successive distances from the hazards were obtained from observed and expected numbers, aggregated over similar sites. This was repeated for different hazard types and results were tested for evidence of systematic centrifugal case density gradients. PARTICIPANTS AND SETTING: All 22,458 children dying from leukaemia or cancer aged 0-15 years, in England, Wales, and Scotland, between 1953 and 1980. MAIN RESULTS: Relative excesses of leukaemias and of solid cancers were found near the following: (1) oil refineries, major oil storage installations, railside oil distribution terminals and factories making bitumen products; (2) motor car factories, coach builders, and car body repairers; (3) major users of petroleum products including manufacturers of solvents, paint sprayers, fibreglass fabricators, paint and varnish makers, plastics and detergent manufacturers, and galvanisers; (4) users of kilns and furnaces including steelworks, power stations, galvanisers, cement makers, brickworks, crematoria and aluminium, zinc, and iron/steel foundries; (5) airfields, railways, motorways and harbours. The findings for leukaemias and for solid cancers were indistinguishable. The hazard proximities of birth addresses were stronger than for death addresses. For children who had moved house between birth and death, the proximity effect was limited to the birth addresses. CONCLUSIONS: Childhood cancers are geographically associated with two main types of industrial atmospheric effluent namely: (1) petroleum derived volatiles and (2) kiln and furnace smoke and gases, and effluents from internal combustion engines.

Spatial clustering of childhood cancers in Great Britain.

STUDY OBJECTIVES: Firstly, to identify spatially close pairs and triplets of childhood leukaemias and cancers in Britain. Secondly, to compare pair frequencies with random expectations, identify excesses, and measure the diameters of any clusters. Thirdly, to infer possible causes. DESIGN AND SETTING: Stratified Poisson analyses of two comprehensive sets of childhood leukaemia and cancer data in Great Britain: seeking home address pairs within particular census enumeration districts (EDs) or postcodes (PCs). Numbers of pairs/triplets of leukaemia registrations sharing single or adjacent EDs were compared with Poisson, expectations in national ED strata with different numbers of households (HHs). Pairs/triplets of leukaemia/cancer deaths (and births) sharing a single PC were compared with Poisson expectations in national PC strata with different numbers of postal delivery points (DPs). Same and adjacent house pairs were identified individually among the same PC death pairs. Areal case densities were estimated around a sample of index cases, using their own PC grid coordinates, and those recorded in the central PC directory. PARTICIPANTS: These comprised, firstly, all cases of childhood leukaemia and non-Hodgkin lymphoma registered between 1966 and 1983 in England and Wales (ED analysis) and, secondly, all childhood leukaemia and cancer deaths between 1953 and 1980, in England, Wales, and Scotland (PC analyses at birth and at death). MAIN RESULTS: Short range spatial clustering was demonstrated (a) for leukaemia at place of registration, and (b) for leukaemia and cancer (separately and jointly) at both birth and death addresses. There was evidence of additional case pairing in adjacent PCs. Both data sets showed a relative local pair excess of about 1.5, within diameters of 300 metres. Secondary case densities, measured within 600 metres of a sample of unpaired index cases, were raised by the same ratio. The raised risk then tapered with increasing distance to about 3 km. Forty-four non-twin pairs had died at exactly the same address, far in excess of random expectation. This same house excess was due entirely to 31 sibling pairs. They also showed a relative excess of central nervous system and other solid tumours; but without the exact tumour type sibling concordances sometimes seen in MZ twins. The sibling pairs were only a small part of the overall excess of same PC pairs. CONCLUSIONS: Short range geographical clustering probably reflects two separate causes of childhood cancer, namely (a) an uncommon familial susceptibility to solid cancers, probably inherited, and (b) a group of long standing focal environmental hazards, most effective within a few hundred metres of the source, but detectable as far as 3 km.

Childhood cancers: space-time distribution in Britain.

STUDY OBJECTIVES: To examine a national data set of all childhood cancers for evidence of space-time interactions within three distinct sets of dates and places (at birth, at diagnosis, and at death), to show whether the patterns found for these events represent separate phenomena or statistically interdependent processes, and to see whether the childhood leukaemias and the childhood solid cancers have separate distinctive patterns in these respects. DESIGN: This was a space-time cluster analysis. The large number of cases enabled division of the data into two sets, one for hypothesis generation and the other for hypothesis testing. SETTING: England, Scotland, and Wales. SUBJECTS: A national collection of 22,360 children aged 0-15 years with fatal cancers and leukaemias in the period 1953 to 1980. MAIN RESULTS: There was significant clustering among the leukaemias and lymphomas on date and place of birth (particularly among cases born within 1 km and up to 5 months apart), and on date and place of diagnosis (particularly among cases diagnosed from 3 to 5 km apart and up to 9 months apart). There was no clustering among the solid cancers. These findings were confirmed in two separate analyses of two separate sets of data. CONCLUSIONS: The birth clustering was significant among pairs diagnosed at differing ages, and diagnosis clustering was significant among pairs born at different times, and it was concluded that the two types of clustering must be regarded as separate and statistically independent phenomena. Both the birth and the diagnosis clusters comprised many independent pairs of cases, with no large multiple case clusters. This suggests the involvement of multiple time-space localised exposures to hazards with short and constant latent intervals; probably an infectious agent or an environmental toxin. Given the separate nature of the two types of clustering, exposure to more than one hazard may be involved.

Migration patterns of children with cancer in Britain.

OBJECTIVES: To investigate the early migration patterns of children who later developed cancer. To test a prior hypothesis that some cancers are initiated by early exposures to toxic atmospheric pollutants from point sources. DESIGN: Address changes in children dying from cancer are examined in relation to potentially hazardous sites of several different types. The relative proximities of birth addresses and death addresses to these sites, are compared. The approach is based upon the premise that a local exposure, effective only at an early age, must be preferentially linked with an early address. SETTING AND SUBJECTS: Records of 22,458 children dying from leukaemia or other cancer under the age of 16 years in Great Britain between 1953 and 1980: including 9224 who moved house between birth and death. The migration analysis was based upon birth and death addresses, converted first to postcodes and thence to map coordinates. The geographical locations of potentially toxic industrial sites were obtained through direct map searches and from commercial directories. RESULTS: Systematic asymmetries were found between measured distances from birth and death addresses to sources emitting volatile organic compounds, or using large scale combustion processes. The children had more often moved away from these hazards than towards them. Many of the sources had already been identified as hazardous using other methods. There was also a birth association with areas of dense habitation; possibly because of unidentified toxic sources contained within them. All forms of cancer were involved although some effluents were associated preferentially with specific types. CONCLUSIONS: The main findings of an earlier study, based upon a different and independent method, were confirmed. Proximities to several types of industrial source, around the time of birth, were followed by a raised risk of childhood cancer. Combustion products and volatile organic compounds were especially implicated. Within the 16 year limit of the study, the increased risk did not decay with advancing age. Low atmospheric concentrations of many carcinogenic substances suggest that the mother acts as a cumulative filter and passes them to the fetus across the placenta or in breast milk.

Effect of anti-inflammatory drugs on overall risk of common cancer: case-control study in general practice research database.

OBJECTIVE: To examine whether anti-inflammatory drug treatment protects against the commoner cancers in the United Kingdom. DESIGN: Case-control study using the general practice research database. SETTING: Practices throughout United Kingdom providing data to the database. SUBJECTS: Patients who had a first diagnosis of five gastrointestinal (oesophagus, stomach, colon, rectum, and pancreas) cancers and four non-gastrointestinal (bladder, breast, lung, and prostate) cancers in 1993-5 for whom prescription data were available for the at least the previous 36 months. Each case was matched for age, sex, and general practice with three controls. MAIN OUTCOME MEASURE: Risk of cancer. RESULTS: In 12 174 cancer cases and 34 934 controls overall risk of the nine cancers was not significantly reduced among those who had received at least seven prescriptions in the 13-36 months before cancer diagnosis (odds ratio 0.98, 95% confidence interval 0.89 to 1.07). Findings were nevertheless compatible with protective effects from anti-inflammatory drugs against cancers of the oesophagus (0.64, 0. 41 to 0.98), stomach (0.51, 0.33 to 0.79), colon (0.76, 0.58 to 1. 00), and rectum (0.75, 0.49 to 1.14) with dose related trends. The risk of pancreatic cancer (1.49, 1.02 to 2.18) and prostatic cancer (1.33, 1.07 to1.64) was increased among patients who had received at least seven prescriptions, but the trend was dose related for only pancreatic cancer. CONCLUSIONS: Anti-inflammatory drugs may protect against oesophageal and gastric cancer as well as colon and rectal cancer. The increased risks of pancreatic and prostatic cancer could be due to chance or to undetected biases and warrant further investigation.

EUHASS: The European Haemophilia Safety Surveillance system.

Pharmacovigilance is an essential element of any drug treatment and considering the history of adverse events due to products used to treat inherited bleeding disorders, it should be an integral component of modern haemophilia treatment. Because inherited bleeding disorders and adverse events are rare, a multicentre, preferably multinational, adverse event reporting scheme for all clotting factor products is required. EUHASS is a European, prospective, multicentre adverse event reporting scheme in the field of inherited bleeding disorders.

Geographical distribution of birth places of children with cancer in the UK.

Using birth addresses, we examined the geographical variation in risk for all types of childhood cancers in the UK, on a scale corresponding to the 10-km squares of the National Grid. The effects of socioeconomic and environmental factors, including natural background radiation, were investigated and their relative importance assessed using Poisson regression. Data came from a national collection of all fatal cancers between 1953 and 1980 in children aged 0-15 years and consisted of 9363 children of known place of birth from 12 complete annual cohorts born in the period 1953-64. For solid cancers, as well as for leukaemias and lymphomas, there was marked variation of cumulative mortality according to place of birth. High mortalities were associated with areas characterized as having high social class, higher incomes and good housing conditions, but also with high population densities (births per hectare). Each of these contrasting social indicators operated independently of the other, indicating complex determining mechanisms. Mortalities increased with increased radon exposure, and the relationship operated independently of the socioeconomic factors. At this scale of analysis, we found no increased mortality in industrialized areas. A population-mixing infective hypothesis, which postulates high rates of leukaemia when highly exposed urban populations are introduced to isolated rural areas, was supported by observations of high mortalities in 'growth areas' and New Towns, but was not readily reconcilable with the high rates seen in the high-density areas. If these correlations do indeed represent an infective mechanism, then the outcomes are not limited to malignancies of the immune system alone.

Injury patterns with snowboarding.

Snowboarding is a winter sport that has shown a considerable increase in popularity during the last 2 decades. As a result, there has been a continued rise in the number of visits to the emergency department (ED) for injuries sustained while snowboarding. Previous studies have concluded that those injured tend to be male, younger, and more inexperienced than their alpine skiing counterparts. This study examines the injury patterns seen in one ED during peak winter sport recreational months over a 5-year period. This retrospective review describes 71 patients with a broad spectrum of injury patterns, but reports a higher incidence of head and spinal injuries than previously documented. Furthermore, recommendations to prevent future injuries as well as education for first responders and physicians regarding the high likelihood of serious injury is discussed.

Descriptive epidemiology of gastrointestinal non-Hodgkin's lymphoma in a population-based registry.

The incidence of non-Hodgkin's lymphoma (NHL), particularly at certain extranodal sites, has been demonstrated to be rising, at least in the USA, more than for any other malignancy. One of the major sites of extranodal NHL is the gastrointestinal tract, though little is known of its epidemiological characteristics. Over an 8-year period (1986 to 1993) 1069 primary gastrointestinal NHL cases were reported to the Leukaemia Research Fund Data Collection Survey which covers many parts of England and Wales. Age-standardized incidence rates of gastrointestinal NHL at all sites (0.58/10(5) per year), gastric (0.24/10(5) per year), small bowel (0.17/10(5) per year) and large bowel (0.06/1(5) per year) confirmed that the UK has the lowest rates of gastrointestinal NHL in Europe. An excess of males was observed at all ages and for all sites. Time-trend analyses showed annual increases in incidence rates for gastric (6.3%) and small bowel (5.9%) NHL although a concomitant decrease in gastrointestinal NHL of unknown site suggested that at least part of these increases had resulted from more accurate diagnoses. Overall, the incidence of gastrointestinal NHL significantly increased by 2.7% per annum and was limited to the population aged over 50 years in this series.

Childhood cancers and their association with pregnancy drugs and illnesses.

In a case/control study of 8059 matched pairs, the effect of maternal exposure to drugs and illnesses during pregnancy on the relative risk (RR) of cancer in the child was investigated using conditional logistic regression techniques. Acute respiratory infections, particularly viral infections such as influenza, were associated with a significantly increased RR of all childhood cancers and of neoplasms of the reticulo-endothelial system (RES) in particular, (RR = 1.69 all cancers, RR = 1.81 RES neoplasms, RR = 1.59 solid cancers). An analysis of illnesses according to their physiological effects yielded a significant association between childhood leukaemia and febrile illnesses (RR = 1.27 RES neoplasms). A significant increase in RR was associated with maternal history of epilepsy (RR = 1.31 all cancers) rather than with exposure to anticonvulsant drugs. Vaccines showed a pattern of RR similar to that of acute viral infections. Consumption of antipyretics and analgesics significantly increased the RR of childhood cancer (RR = 1.36 all cancers). An analysis of drugs according to their metabolic reactions yielded a significant association between those undergoing amino acid conjugation (predominantly antipyretics and analgesics) and childhood cancer risk (RR = 1.76 solid cancers).

The onset of the excess of childhood cancer in Seascale, Cumbria.

BACKGROUND: The objective of this study was to formally investigate the onset of the Seascale cluster of childhood and young person's cancer. This has not previously been attempted. METHODS: A mortality study within the Whitehaven registration district was set up and death records were abstracted for 1906-1970. They were categorized as death from leukaemias, lymphomas, other cancers and all other causes in persons aged 0-14, 0-24 and 25-84. The number of deaths, death rates and standardized mortality ratios were calculated. RESULTS: The mortality of persons aged 25-84 in Seascale civil parish, Gosforth civil parish and the rest of the Whitehaven district was unremarkable compared with national data 1906-1970. There were no cancer deaths aged 0-24 in Gosforth civil parish during 1906-1970. In Seascale civil parish a hitherto unrecorded childhood cancer case was revealed, dying in 1954. No cancer deaths aged 0-24 were found before that date. In the period 1946-1955 three cancer deaths gave a statistically significant excess owing to non-leukaemia cases, whereas in the period 1956-1965 a statistical excess of all types of leukaemia occurred as a result of two deaths. There was no case excess (based on one leukaemia death) in the period 1966-1970. CONCLUSION: We found no clear temporal associations of the case excesses either with the periods of significant nuclear activity on the Sellafield site or with the main periods of population growth in the area.

Leukaemia incidence near coastal features.

BACKGROUND: The aim of the study was to independently test the hypothesis that leukaemia incidence is higher in proximity to estuaries. METHODS: Electoral wards were classified as to whether they included estuarine, coastal or only inland features. Rates of different adult and childhood leukaemias were computed for each ward category; that is, acute lymphoblastic leukaemia (ALL), acute myeloid leukaemia (AML), chronic myeloid leukaemia (CML) aged 0-79 and for all childhood leukaemias combined (aged 0-14). RESULTS: Poisson regression analysis controlling for the effects of sex, age, and socioeconomic and urban-rural status, showed no statistically significant differences in incidence between wards with different levels of estuarine classification. CONCLUSION: The hypothesis created from an earlier dataset that a link exists between leukaemia and residence near estuaries is not upheld.

Epidemiology of multiple myeloma in parts of England, 1984-1993.

This paper presents a new analysis of aspects of the descriptive epidemiology of multiple myeloma (MM) for parts of the U.K., 1984-1993. It provides no indication for geographical heterogeneity, nor is there evidence of a decline in rates over the decade. There is, however, evidence that cancer registration inflates MM rates in the elderly.

Home antipyretic use in children brought to the emergency department.

OBJECTIVE: To determine how often children with a complaint of fever receive antipyretics at home and if any demographic factors are associated with correct dosing. METHODS: A prospective, descriptive study of children 3 to 36 months old presenting with complaint of fever was conducted. Caregivers were questioned about demographics and antipyretic given. The ability of demographics to predict proper dosing was tested first individually and then with a regression model. The effect of proper home dosing on presence of fever and height of fever was also analyzed. A total of 138 children were analyzed. RESULTS: Of the 118 (86%) who received antipyretics at home, only 47% had been given a proper dose. No demographic variable predicted proper dosing. CONCLUSION: Reported antipyretic dose at home did not predict presence of fever or height of temperature measured in the emergency department.