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Biomedical subjects

E G Knox

Publications and source records attributed to E G Knox.

At least 19 recordsLinked to original sources
PubMed1998

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.

Adolescent↗
PubMed1997

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.

Adolescent↗
PubMed1996

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.

Adolescent↗
PubMed1995

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.

Adolescent↗
PubMed1994

Leukaemia clusters in childhood: geographical analysis in Britain.

STUDY OBJECTIVE: To validate previously demonstrated spatial clustering of childhood leukaemias by showing relative proximities of selected map features to cluster locations, compared with control locations. If clusters are real, then they are likely to be close to a determining hazard. DESIGN: Cluster postcode loci and partially matched control postcodes were compared in terms of distances to railways, main roads, churches, surface water, woodland areas, and railside industrial installations. Further supporting comparisons between non-clustered cases and random postcode controls with those map features representable as single grid points were made. SETTING: England, Wales, and Scotland 1966-83. SUBJECTS: Grid referenced registrations of 9406 childhood leukaemias and non-Hodgkin's lymphomas, including 264 pairs (or more) separated by < 150 m, and grid references of random postcodes in equal numbers. MAIN RESULTS: The 264 clusters showed relative proximities (or the inverse) to several map features, of which the most powerful was an association with railways. The non-railway associations seemed to be statistically indirect. Some railside industrial installations, identified from a railway atlas, also showed relative proximities to leukaemia clusters, as well as to non-clustered cases, but did not "explain" the railway effect. These installations, with seemingly independent geographical associations, included oil refineries, petrochemical plants, oil storage and oil distribution depots, power stations, and steelworks. CONCLUSIONS: The previously shown childhood leukaemia clusters are confirmed to be non-random through their systematic associations with certain map features when compared with the control locations. The common patterns of close association of clustered and non-clustered cases imply a common aetiological component arising from a common environmental hazard--namely the use of fossil fuels, especially petroleum.

Adolescent↗
PubMed1993

Accidental dural puncture in obstetric patients and long term symptoms.

OBJECTIVE: To examine the association between accidental dural puncture and long term headache and related symptoms. DESIGN: Postal questionnaire survey to elucidate new symptoms occurring after childbirth, and linking of these to data in obstetric and anaesthetic case notes. Women were surveyed between 13 months and nine years after delivery. SETTING: Birmingham Maternity Hospital. SUBJECTS: 4700 women who had delivered their most recent baby under epidural anaesthesia, 74 of whom had suffered an accidental dural puncture. MAIN OUTCOME MEASURES: Frequencies of new headache or migraine or neck ache starting within three months after childbirth and lasting over six weeks. RESULTS: Among the 74 women who had had an accidental dural puncture there were 17 (23%) who reported one or more of the above symptoms. By comparison, among those who had had an epidural anaesthetic but no recorded puncture, only 329 (7.1%) reported these symptoms. The duration of the headache or migraine or neck ache in the dural tap group ranged from nine weeks to over eight years. Ten of these women reported still unresolved symptoms. CONCLUSIONS: Conclusions on causality were tentative. Most women would remember a dural tap, and this might influence their reporting of subsequent symptoms attributable to the event. In addition, detailed characterisation of the symptoms was not available. Nevertheless, the findings provide a clear indication of the need for further study of the possible long term sequelae of accidental dural puncture.

Accidents↗
PubMed1993

Comparison of long-term health problems following childbirth among Asian and Caucasian mothers.

While obstetric problems in Asian women have been documented, little is known about longer term health problems following childbirth. This study compares long-term postpartum morbidity in Asian and Caucasian women who had had an infant at a Birmingham maternity unit between 1978 and 1985. A total of 11,701 women returned the questionnaire asking about their experience of a list of 25 health problems. It was found that backache, frequent headaches, shoulderache and pains and weakness in the arms and legs all occurred more commonly among the 530 Asian women than in Caucasian women, even after standardizing for confounding factors. All these symptoms started within three months of the birth, lasted more than six weeks and had not previously been experienced. Most symptoms persisted for more than a year, and even after several years, many had not resolved. The possible role of vitamin D deficiency and the value of antenatal vitamin D supplements are discussed.

Adult↗
PubMed1992

Investigation of long term problems after obstetric epidural anaesthesia.

OBJECTIVE: To examine the association between obstetric epidural anaesthesia and subsequent long term problems. DESIGN: Postal questionnaire on health problems after childbirth linked to maternity case note data. SETTING: Maternity hospital in Birmingham. SUBJECTS: 11701 women who delivered their most recent child during 1978-85 and who returned completed questionnaires. MAIN OUTCOME MEASURES: Frequencies of long term symptoms after childbirth. RESULTS: Compared with the 6935 women who did not have epidural anaesthesia the 4766 women who did more commonly experienced backache (903 (18.9%) with epidural v 731 (10.5%) without epidural), frequent headaches 220 (4.6%) v 199 (2.9%)), migraine (92 (1.9%) v 73 (1.1%)), neckache (116 (2.4%) v 112 (1.6%)), and tingling in hands or fingers (143 (3.0%) v 150 (2.2%)). The results could not be explained by correlated social or obstetric factors. The associations with head, neck, and hand symptoms were found only in women who reported backache. An excess of visual disturbances among women who had epidural anaesthesia (83 (1.7%) v 91 (1.3%)) was present only in association with migraine, but excess of dizziness or fainting (102 (2.1%) v 109 (1.6%)) was independent of other symptoms. 26 women had numbness or tingling in the lower back, buttocks, and leg, of whom 23 had had epidural anaesthesia. Of 34 women with spinal headache, nine (five after accidental dural puncture; four after spinal block) reported long term headaches. CONCLUSIONS: These associations may indicate a causal sequence, although this cannot be proved from this type of study. Randomised trials of epidural anaesthesia are required to determine whether causal relations exist.

Adult↗
PubMed1992

Leukaemia clusters in Great Britain. 1. Space-time interactions.

STUDY OBJECTIVE: The aim was to test a large set of childhood leukaemia and lymphoma registrations for the presence of clusters in space and in time. DESIGN: The study was a space-time cluster analysis. SETTING: England, Wales and Scotland. PATIENTS: All registrations for leukaemia and lymphoma between 1966 and 1983 in children aged 0 to 14 years were examined. The records included date and age of registration, sex, diagnosis, and the map reference of the postcode of residence. Of the 9411 registrations, 8888 were suitable for inclusion. MAIN RESULTS: There was a statistically significant excess of case pairs occurring jointly within 0.5 km and 60 d of each other: 68 pairs compared with 50.0 expected. The excess was detectable in central England, in the north of England and Scotland, but not in the south west of England. It was concentrated within the age band 4 to 7 years and among the lymphatic leukaemias. Several potential artefacts were considered and excluded, but the possibility remained that clustered detections might be triggered by haematological examinations undertaken for some communicable disease. CONCLUSIONS: There was strong evidence of joint spatial-temporal clustering, with an excess of pairs separated by very short time and distance intervals. The causes are probably biological rather than artefactual, but further work will be necessary in order to exclude the latter.

Adolescent↗
PubMed1992

Leukaemia clusters in Great Britain. 2. Geographical concentrations.

STUDY OBJECTIVE: The aim was to test a large set of childhood leukaemia and lymphoma registrations for the presence of short radius spacial clusters. DESIGN: The study was a geographical cluster analysis. SETTING: England, Wales and Scotland. PATIENTS: All registrations for leukaemia and lymphoma between 1966 and 1983 in children aged 0 to 14 years were examined. The records included date and age of registration, sex, diagnosis, and the map reference of the postcode of residence. Of the 9411 registrations, 8888 were suitable for inclusion. MAIN RESULTS: There was a significant excess of case pair addresses separated by < 0.5 km. There was also a significant excess of pairs sharing the same postcode. Both findings were based upon comparison with random pairs of postcodes drawn from the Central Postcode Directory. Examination for clustering at this very short range was based upon a clear prior hypothesis derived from the results of a study of space-time interaction, reported in a companion paper. CONCLUSIONS: It is postulated that the space-time interaction and the geographical concentrations shown here result from a common epidemic process. The epidemiology of this disease is characterised by short range geographical concentrations, with temporal non-homogeneity superimposed. The findings exclude certain artefacts which remained unresolved in the space-time interaction study. The distributions almost certainly reflect biological processes, and the most probable explanation is in terms of an infective process.

Adolescent↗
PubMed1991

Cot deaths in Birmingham.

The spatial and temporal distributions of cot deaths and of infant respiratory deaths in Birmingham between 1964 and 1984 were examined. Respiratory deaths declined and cot deaths increased, and the combined rate showed a downward trend. Seasonal variations were identical in the two groups and in each case were more powerfully related to date of death than to date of birth. Cumulative mortalities were parallel by age, depended crucially upon the quarter of the year in which the child was born, and were identical for the two classes of death. The separation of the temporal trends probably owed more to changes in diagnostic practice than to biological or epidemiological processes. Powerful space-time interactions were detected for both groups and for cross-pairs belonging to different groups. There was a four-yearly oscillation in the combined death rate, of doubtful statistical significance, but synchronous with a similar oscillation reported by other investigators using national data. The four-yearly oscillation was also synchronous with the four-yearly pattern for national isolations of Mycoplasma pneumoniae.

Age Factors↗
PubMed1990

Epidural anaesthesia and long term backache after childbirth.

OBJECTIVE: To examine the relation between epidural anaesthesia and long term backache after childbirth. DESIGN: Data from postal questionnaire on morbidity after childbirth sent to women who had delivered in one maternity hospital between 1978 and 1985 were linked to maternity case notes for each woman. SETTING: Maternity hospital in Birmingham. SUBJECTS: 11,701 Women who had delivered their most recent baby at the maternity hospital during the defined period and who returned their completed questionnaires. MAIN OUTCOME MEASURES AND RESULTS: Of the 1634 women who reported backache, 1132 (69%) had had it for over a year. A significant association was found between backache and epidural anaesthesia (relative risk = 1.8); 903 of 4766 women (18.9%) who had had epidural anaesthesia reported this symptom, compared with 731 of the 6935 women (10.5%) who had not had epidural anaesthesia. This association was consistent in both "normal" and "abnormal" deliveries, the only exception being after an elective caesarean section when no excess backache occurred after epidural anaesthesia. CONCLUSIONS: The relation between backache and epidural anaesthesia is probably causal. It seems to result from a combination of effective analgesia and stressed posture during labour. Further investigations on the mechanisms causing backache after epidural anaesthesia are required.

Anesthesia, Epidural↗
PubMed1988

Evaluation of a proposed breast cancer screening regimen.

The Forrest working group on breast cancer screening recommended routine mammography for women in the United Kingdom at ages 50, 53, 56, 59, 62, and 65. Benefits were costed at about 3000 pounds for each life year recovered, but there was no estimate of the cost of each life saved, and the consequent reduction in mortality from breast cancer in the general population of the United Kingdom was not estimated. The present study addressed both of these issues using an interactive computer modelling process. Long term savings were calculated at 900 deaths a year in England and Wales--that is, about 8% of the total deaths from breast cancer--and 9% of life years currently lost. The cost of each death saved from breast cancer was estimated at 39,000 pounds.

Age Factors↗
PubMed1988

Cancer of the cervix and the papilloma viruses.

Squamous cancer of the cervix depends upon infection by Human Papilloma Virus (HPV), of which there are many strains. Some are more dangerous than others and they appear to compete with each other for "territory". The prospective use of vaccines and antiviral agents for HPV infection could disturb the balance of this ecosystem. This study derives the expressions for the prevalences of the different strains at equilibrium. The important parameters of these expressions are 1) the rate of change of sexual partner, 2) infectiousness on contact, and 3) the rates at which an infectious/immune phase decays to a non-infectious/immune phase, and then towards partial or full susceptibility to re-infection. The responses to changes in these parameters are investigated. Analysis shows that the balance between competing strains is locally and precariously stable; it can survive moderate inter-strain variations of the transmission and decay parameters; but larger differences, whether natural or artificially induced, can result in the rapid elimination of the disadvantaged strain. This might be exploited in a preventive programme. Conversely, if a harmless strain were eliminated, the harmful strains would fill the territorial gap, and the incidence of cervical cancer might increase.

Carcinoma, Squamous Cell↗
PubMed1988

Smoking in pregnancy: effects of stopping at different stages.

Of 4341 pregnant women, 3106 were non-smokers and 1235 were smokers at the start of pregnancy. Eighty-five had stopped smoking before 6 weeks gestation, 119 between 6 and 16 weeks, and 56 stopped after 16 weeks. A further 51 stopped temporarily and 924 smoked throughout pregnancy. The mean birthweight of the groups differed. There were also social and biological differences such as might partly explain birthweight variations so comparisons were repeated after allowing for these factors. Standardized mean birthweights were greater for all groups who stopped than for persistent smokers. Those who stopped before 6 weeks and between 6 and 16 weeks gestation had infants 217 and 213 g, respectively, heavier than the persistent smokers and similar to the non-smokers. Babies born to those who stopped after 16 weeks, or temporarily, were intermediate in weight. Appropriate advice is that stopping any time before 16 weeks is best, but stopping after this is still beneficial.

Adult↗