Co-designed weight management intervention for women recovering from oestrogen-receptor positive breast cancer.

BACKGROUND: Weight gain is commonly observed during and after breast cancer treatment and is associated with poorer survival outcomes, particularly in women with oestrogen receptor-positive (ER +) disease. The aim of this study was to co-design (with patients) a programme of tailored, personalised support (intervention), including high-quality support materials, to help female breast cancer patients (BCPs) with ER + disease to develop the skills and confidence needed for sustainable weight loss.  METHODS: ER + BCPs were recruited from two UK National Health Service (NHS) Trusts. The selection criteria included (i) recent experience of breast cancer treatment (within 36 months of completing primary treatment); (ii) participation in a recent focus group study investigating weight management perceptions and experiences; (iii) willingness to share experiences and contribute to discussions on the support structures needed for sustainable dietary and physical activity behaviour change. Co-design workshops included presentations and interactive activities and were facilitated by an experienced co-design researcher (HH), assisted by other members of the research team (KP, SW and JS). RESULTS: Two groups of BCPs from the North of England (N = 4) and South Yorkshire (N = 5) participated in a two-stage co-design process. The stage 1 and stage 2 co-design workshops were held two weeks apart and took place between Jan-March 2019, with each workshop being approximately 2 h in duration. Guided by the Behaviour Change Wheel, a theoretically-informed weight management intervention was developed on the basis of co-designed strategies to overcome physical and emotional barriers to dietary and physical activity behaviour change. BCPs were instrumental in designing all key features of the intervention, in terms of Capability (e.g., evidence-based information, peer-support and shared experiences), Opportunity (e.g., flexible approach to weight management based on core principles) and Motivation (e.g., appropriate use of goal-setting and high-quality resources, including motivational factsheets) for behaviour change. CONCLUSION: This co-design approach enabled the development of a theoretically-informed intervention with a content, structure and delivery model that has the potential to address the weight management challenges faced by BCPs diagnosed with ER + disease. Future research is required to evaluate the effectiveness of the intervention for eliciting clinically-important and sustainable weight loss in this population.

Does regional loss of bone density explain low trauma distal forearm fractures in men (the Mr F study)?

The pathogenesis of low trauma wrist fractures in men is not fully understood. This study found that these men have lower bone mineral density at the forearm itself, as well as the hip and spine, and has shown that forearm bone mineral density is the best predictor of wrist fracture. INTRODUCTION: Men with distal forearm fractures have reduced bone density at the lumbar spine and hip sites, an increased risk of osteoporosis and a higher incidence of further fractures. The aim of this case-control study was to investigate whether or not there is a regional loss of bone mineral density (BMD) at the forearm between men with and without distal forearm fractures. METHODS: Sixty-one men with low trauma distal forearm fracture and 59 age-matched bone healthy control subjects were recruited. All subjects underwent a DXA scan of forearm, hip and spine, biochemical investigations, health questionnaires, SF-36v2 and Fracture Risk Assessment Tool (FRAX). The non-fractured arm was investigated in subjects with fracture and both forearms in control subjects. RESULTS: BMD was significantly lower at the ultradistal forearm in men with fracture compared to control subjects, in both the dominant (mean (SD) 0.386 g/cm2 (0.049) versus 0.436 g/cm2 (0.054), p < 0.001) and non-dominant arm (mean (SD) 0.387 g/cm2 (0.060) versus 0.432 g/cm2 (0.061), p = 0.001). Fracture subjects also had a significantly lower BMD at hip and spine sites compared with control subjects. Logistic regression analysis showed that the best predictor of forearm fracture was ultradistal forearm BMD (OR = 0.871 (0.805-0.943), p = 0.001), with the likelihood of fracture decreasing by 12.9% for every 0.01 g/cm2 increase in ultradistal forearm BMD. CONCLUSIONS: Men with low trauma distal forearm fracture have significantly lower regional BMD at the ultradistal forearm, which contributes to an increased forearm fracture risk. They also have generalised reduction in BMD, so that low trauma forearm fractures in men should be considered as indicator fractures for osteoporosis.

Incidence and survival of children and young people with central nervous system embryonal tumours in the North of England, 1990-2013.

BACKGROUND: Medulloblastoma and primitive neuroectodermal tumours (PNET) are the most common central nervous system (CNS) embryonal tumours diagnosed in childhood. Survival outcomes are worse for children diagnosed with CNS PNET compared to medulloblastoma. Less is known about survival outcomes in teenagers and young adults (TYA). METHODS: Data were extracted from two population-based cancer registries of children and young people (0-24 years) in the north of England for all diagnoses of medulloblastoma and CNS PNET between 1990 and 2013. Incidence and survival trends were analysed using Poisson and Cox regression. RESULTS: Between 1990 and 2013, 197 medulloblastomas and 58 CNS PNET were diagnosed, age-standardised incidence rates of 3.8 and 1.5 per million, respectively. Medulloblastoma incidence decreased over time while there was no significant change in trend for CNS PNET. The overall 5-year survival rate was 54%. The risk of death was 2.4 times higher (95% confidence interval [CI] 1.6, 3.7) for patients with CNS PNET compared to medulloblastoma, after adjustment for patient characteristics. There was a 39% reduction (95% CI 0.43, 0.87) in the risk of death for patients diagnosed between 2000 and 2013 compared to 1990-1999. Risk of death did not differ for TYA (15-24 years) compared to children aged 5-9 years. CONCLUSIONS: Medulloblastoma incidence decreased over time and differences in survival between medulloblastoma and PNET emerged within the first-year post diagnosis leading to poorer outcomes for children and young adults diagnosed with PNET; however, a significant improvement in survival over time was observed.

Updated investigations of cancer excesses in individuals born or resident in the vicinity of Sellafield and Dounreay.

BACKGROUND: Earlier studies have shown raised risks of leukaemia and non-Hodgkin lymphoma in children, teenagers and young adults resident either at birth or diagnosis in Seascale. Some increases in cancer risk in these age groups have also been noted among those living around Dounreay. We aimed to update previous analyses relating to areas close to these nuclear installations by considering data from an additional 16 years of follow-up. METHODS: Cross-sectional analyses compared cancer incidence rates for 1963-2006 among those aged 0-24 years at diagnosis living in geographically specified areas around either Sellafield or Dounreay with general population rates. Cancer incidence for the period 1971-2006 among the cohort of Cumbrian births between 1950 and 2006 was compared to national incidence for 1971-2006 using person-years analysis. Cancer among those born in the postcode sector closest to Dounreay was compared with that among those born in the three adjoining postcode sectors. Analyses considered both cancer overall and ICD-O-3 defined diagnostic subgroups including leukaemia, central nervous system tumours and other malignancies. RESULTS: Apart from previously reported raised risks, no new significantly increased risks for cancer overall or any diagnostic subgroup were found among children or teenagers and young adults living around either nuclear installation. Individuals born close to the installations from 1950 to 2006 were not shown to be at any increased risk of cancer during the period 1971 to date. CONCLUSIONS: Analysis of recent data suggests that children, teenagers and young adults currently living close to Sellafield and Dounreay are not at an increased risk of developing cancer. Equally, there is no evidence of any increased cancer risk later in life among those resident in these areas at birth.

Survival from teenage and young adult cancer in Northern England, 1968-2008.

BACKGROUND: Although cancer is relatively rare in teenagers and young adults (TYAs) aged 15-24 years, it is a major cause of death in this age group. This study investigated survival trends in TYA cancer diagnosed in Northern England, 1968-2008. METHODS: Five-year survival was analyzed using Kaplan-Meier estimation for four successive time periods. Cox regression analysis was used to investigate associations with demographic factors. RESULTS: The study included 2,987 cases (1,634 males, 1,353 females). Five-year survival for all patients with cancer improved greatly from 46% in 1968-1977 to 84% in 1998-2008 (P < 0.001), for patients with leukemia from 2% to 71% (P < 0.001), lymphoma from 66% to 86% (P < 0.001), central nervous system tumors from 53% to 84% (P < 0.001), bone tumors from 29% to 72% (P < 0.001), germ cell tumors from 39% to 94% (P < 0.001), melanoma and skin cancer from 64% to 100% (P < 0.001), and carcinomas from 48% to 80% (P < 0.001). Cox analysis showed that for all patients with cancer, survival was better for females than males (HR = 0.83; 95% CI 0.74-0.94, P < 0.001), for patients aged 20-24 years compared with those aged 15-19 years (HR = 0.84; 95% CI 0.75-0.94, P = 0.002), but survival was worse for patients who resided in more deprived areas (HR = 1.06; 95% CI 1.01-1.11, P = 0.025). CONCLUSION: There have been large improvements in TYA cancer survival in Northern England over the last four decades. Future work should determine factors that could lead to even better survival, including possible links with delayed diagnosis.

Management of complex colonic polyps in the English Bowel Cancer Screening Programme.

BACKGROUND: Large sessile or flat colonic polyps, defined as polyps at least 20 mm in size, are difficult to treat endoscopically and may harbour malignancy. The aim of this study was to describe their current management to provide insight into optimal management. METHODS: This retrospective observational study identified patients with large sessile or flat polyps detected in the English Bowel Cancer Screening Programme between 2006 and 2009. Initial therapeutic modality (surgical or endoscopic), subsequent management and outcomes were recorded. The main outcome measures analysed were: presence of malignancy, need for surgical treatment, complications, and residual or recurrent polyp at 12 months. RESULTS: In total, 557 large sessile or flat polyps with benign appearance or initial histology were identified in 557 patients. Some 436 (78.3 per cent) were initially managed endoscopically and 121 (21.7 per cent) were managed surgically from the outset. Seventy of those initially treated endoscopically subsequently required surgery owing to the presence of malignancy (19) or not being suitable for further endoscopic management (51). Residual or recurrent polyp was present at 12 months in 26 (6.0 per cent) of 436 patients managed endoscopically. There was wide variation between centres in the use of surgery as a primary therapy, ranging from 7 to 36 per cent. Endoscopic complications included bleeding in 13 patients (3.0 per cent) and perforation in two (0.5 per cent). CONCLUSION: Management of large sessile or flat colonic polyps is safe and effective in the English Bowel Cancer Screening Programme. Wide variation in the use of surgery suggests a need for standardized management algorithms. Presented to a meeting of the British Society of Gastroenterology, Birmingham, U.K., March 2011.

Outcome of 12-month surveillance colonoscopy in high-risk patients in the National Health Service Bowel Cancer Screening Programme.

AIM: Current British guidelines recommend surveillance colonoscopy at 12 months for individuals found to have five or more adenomas, or three or more adenomas of which at least one is ≥ 1 cm in size. This study describes the yield of surveillance colonoscopy in this group and explores patient and clinical factors that may be associated with the presence of advanced adenomas or cancer at surveillance. METHOD: Data were retrieved from the national database of the National Health Service Bowel Cancer Screening Programme. The detection of advanced colonic neoplasia (ACN, cancer or advanced adenoma) was used as the main outcome variable. Multivariable analysis was used to analyse relationships between patient factors (age, gender, body mass index, smoking and alcohol use) and clinical findings (number, size and nature of adenomas detected during index colonoscopy) with the outcome variable. RESULTS: One-thousand, seven-hundred and sixty individuals were included in the study. The yield of ACN at 12-month surveillance was 6.6% (116/1760), of which 14/1760 (0.8%) had colorectal cancer. Nine (64.3%) of these 14 cancers were Dukes A at diagnosis. The presence of a villous adenoma or a right-sided adenoma at screening colonoscopy was associated with ORs of 1.98 (95% CI: 1.11-3.53, P = 0.012) and 1.76 (95% CI: 1.13-2.74, P = 0.020), respectively, for detection of ACN at surveillance. CONCLUSION: Twelve-month surveillance colonoscopy is necessary in this group of patients. The presence of villous or proximal lesions at baseline is associated with increased risk of ACN at surveillance. Site and histological type of baseline lesions may be relevant for determining the surveillance interval.

Socioeconomic variation in survival from childhood leukaemia in northern England, 1968-2010.

BACKGROUND: Despite marked improvements in childhood leukaemia survival, 20% still die within 5 years of diagnosis. The aim of this study was to evaluate the relationship between socioeconomic status, as assessed by paternal occupation at birth, and survival from childhood leukaemia in children, using data from the Northern Region Young Persons Malignant Disease Registry. METHODS: All 1007 cases of leukaemia in children aged 0-14 years, diagnosed between 1968 and 2010 and registered with the Registry were studied. Paternal occupational social class at the time of the child's birth was obtained and analysed in relation to survival using Cox-proportional regression. RESULTS: Compared with the most advantaged group (I/II), those in the middle group (IIIN/M) had a 68% increased risk of death, while those in the least advantaged group (IV/V) had 86% higher risk for acute lymphoblastic leukaemia. While the survival advantage of children in class I/II was apparent from the time of diagnosis, survival for children in groups IIIN/M and IV/V were comparable until 3-4 years after diagnosis, when they began to minimally diverge. CONCLUSION: The existence of such socioeconomic disparities cannot be attributed to accessibility to health care in the United Kingdom. Further research into the likely factors underlying these disparities is required.

Spatial clustering of childhood acute lymphoblastic leukaemia in hungary.

The aetiology of childhood acute lymphoblastic leukaemia has been linked with spatially heterogeneous environmental exposures. The presence of spatial clustering would be consistent with geographically localized environmental exposures over long periods of time. The present study is the first to examine spatial clustering amongst children aged 0-4 years using population-based data from Hungary. The data set consisted of 134 children diagnosed with acute lymphoblastic leukaemia who were resident in part of Hungary during the period 1981-2000. Two levels of spatial aggregation were examined: counties and settlements. The Potthoff-Whittinghill and Moran I autocorrelation methods were used to test for spatial clustering. Additionally, an evaluation of the environmental changes during the study period was considered. Specifically analyses were carried out on sub-periods to investigate a possible effect of the Chernobyl catastrophe. There was statistically significant spatial clustering both at the county (estimate of extra-Poisson variation [Formula: see text], P = 0.04) and settlement levels (estimate of extra-Poisson variation [Formula: see text], P = 0.0003). At county level, the finding was attributable to clustering amongst female cases, but at settlement level, the finding was limited to male cases. There was significant spatial autocorrelation in the sub-periods immediately following the accident (1986-1990 & 1991-1995), but not before 1986, nor after 1995. A significant autocorrelation was observed during the 5 year period immediately following the accident (1986-1990, global Moran I = 0.1334, p = 0.005). The centre of significant excesses of ALL cases was located in the county of Baranya. Our study is consistent with an environmental aetiology for acute lymphoblastic leukaemia in children associated with constant exposure to an, as yet unknown, environmental factor in small geographical areas. Although a possible effect of the Chernobyl accident was found in the autocorrelation analysis, the role of chance cannot be excluded.

Longer mean colonoscopy withdrawal time is associated with increased adenoma detection: evidence from the Bowel Cancer Screening Programme in England.

BACKGROUND AND STUDY AIMS: Increasing colonoscopy withdrawal time (CWT) is thought to be associated with increasing adenoma detection rate (ADR). Current English guidelines recommend a minimum CWT of 6 minutes. It is known that in the Bowel Cancer Screening Programme (BCSP) in England there is wide variation in CWT. The aim of this observational study was to examine the relationship between CWT and ADR. PATIENTS AND METHODS: The study examined data from 31 088 colonoscopies by 147 screening program colonoscopists. Colonoscopists were grouped in four levels of mean CWT ( < 7, 7 - 8.9, 9 - 10.9, and ≥ 11 minutes). Univariable and multivariable analysis (binary logistic and negative binomial regression) were used to explore the relationship between CWT, ADR, mean number of adenomas and number of right-sided and advanced adenomas. RESULTS: In colonoscopists with a mean CWT < 7 minutes, the mean ADR was 42.5 % compared with 47.1 % in the ≥ 11-minute group (P < 0.001). The mean number of adenomas detected per procedure increased from 0.77 to 0.94, respectively (P < 0.001). The increase in adenoma detection was mainly of subcentimeter or proximal adenomas; there was no increase in the detection of advanced adenomas. Regression models showed an increase in ADR from 43 % to 46.5 % for mean CWT times ranging from 6 to 10 minutes. CONCLUSIONS: This study demonstrates that longer mean withdrawal times are associated with increasing adenoma detection, mainly of small or right-sided adenomas. However, beyond 10 minutes the increase in ADR is minimal. Mean withdrawal times longer than 6 minutes are not associated with increased detection of advanced adenomas. Withdrawal time remains an important quality metric of colonoscopy.

Survival from childhood cancer in northern England, 1968-2005.

BACKGROUND: Cancer is the second most common cause of death in children in the developed world. The study investigated patterns and trends in survival from childhood cancer in patients from northern England diagnosed 1968-2005. METHODS: Five-year survival was analysed using Kaplan-Meier estimation for four successive time periods. Cox regression analysis was used to explore associations with age and demographic factors. RESULTS: The study included 2958 cases (1659 males and 1299 females). Five-year survival for all cancers improved significantly from 39% in 1968-1977 to 79% in 1998-2005 (P<0.001). Five-year survival for leukaemia increased from 24% to 81% (P<0.001), lymphoma from 46% to 87% (P<0.001), central nervous system tumours from 43% to 73% (P<0.001), bone tumours from 21% to 75% (P<0.001), soft tissue sarcoma from 30% to 58% (P<0.001) and germ cell tumours from 59% to 97% (P<0.001). Survival was worse for cases of acute lymphoblastic leukaemia (P<0.001) and astrocytoma (P<0.001) aged 10-14 years compared with 0-4-year olds. CONCLUSION: There were marked improvements in survival over a 38-year time span. Future work should examine factors that could influence further improvement in survival such as diagnosis delays.

Incidence and survival of childhood bone cancer in northern England and the West Midlands, 1981-2002.

There is a paucity of population-based studies examining incidence and survival trends in childhood bone tumours. We used high quality data from four population-based registries in England. Incidence patterns and trends were described using Poisson regression. Survival trends were analysed using Cox regression. There were 374 cases of childhood (ages 0-14 years) bone tumours (206 osteosarcomas, 144 Ewing sarcomas, 16 chondrosarcomas, 8 other bone tumours) registered in the period 1981-2002. Overall incidence (per million person years) rates were 2.63 (95% confidence interval (CI) 2.27-2.99) for osteosarcoma, 1.90 (1.58-2.21) for Ewing sarcoma and 0.21 (0.11-0.31) for chondrosarcoma. Incidence of Ewing sarcoma declined at an average rate of 3.1% (95% CI 0.6-5.6) per annum (P=0.04), which may be due to tumour reclassification, but there was no change in osteosarcoma incidence. Survival showed marked improvement over the 20 years (1981-2000) for Ewing sarcoma (hazard ratio (HR) per annum=0.95 95% CI 0.91-0.99; P=0.02). However, no improvement was seen for osteosarcoma patients (HR per annum=1.02 95% CI 0.98-1.05; P=0.35) over this time period. Reasons for failure to improve survival including potential delays in diagnosis, accrual to trials, adherence to therapy and lack of improvement in treatment strategies all need to be considered.

Evidence of an environmental contribution to the aetiology of cryptorchidism and hypospadias?

OBJECTIVES: Evidence suggests that there is geographical variation in the birth prevalence of both cryptorchidism and hypospadias. The aim was to determine if there is evidence of spatial heterogeneity in the prevalence of these conditions and to test the hypothesis that environmental factors may contribute to aetiology. METHODS: A population-based dataset of cryptorchidism and hypospadias cases was constructed from the hospital episodes statistics that covered the Northern Region of England and assigned to a small area based on the residential address at time of admission. Expected numbers of cases for each small area were computed. The ratio of observed to expected cases was determined for each small area and analysed with respect to both geographical heterogeneity and small area level socio-economic deprivation. The Potthoff-Whittinghill method was used to determine if there was localized spatial clustering of cases. RESULTS: There was statistically significant spatial clustering for cases of both cryptorchidism [estimated Extra-Poisson Variation (EPV) = 0.14; 95% CI, 0.03-0.25] and hypospadias (EPV = 0.17; 95% CI, 0.05-0.28). In addition, increased prevalence was associated with lower levels of deprivation for hypospadias (P = 0.06), but there was no such relationship for cryptorchidism (P = 0.61). CONCLUSIONS: The finding of localized spatial heterogeneity in the prevalence of cryptorchidism and hypospadias is consistent with the involvement of a spatially varying environmental risk factor. The apparent social patterning of hypospadias is likely to reflect an association with lifestyle and other factors which underpin social variation in health. However, there also remains a possibility that these findings may be due to variability in ascertainment of cases.

Birth prevalence of cryptorchidism and hypospadias in northern England, 1993-2000.

AIM: There is much debate as to whether the prevalence rates of cryptorchidism and hypospadias are increasing. To address this issue we investigated the birth prevalence of cryptorchidism and hypospadias in the northern region of England during the period 1993-2000. METHODS: Cases of cryptorchidism and hypospadias were identified from northern region hospital episodes statistics (HES). Trends in birth prevalence, based on the number of male live births, were assessed using linear regression. RESULTS: Prevalence was 7.6 per 1000 male live births for cryptorchidism and 3.1 per 1000 male live births for hypospadias. The orchidopexy rates for 0-4 year olds and 5-14 year olds were 1.8 and 0.8 per 1000 male population, respectively. The rates for hypospadias repair for 0-4 year olds and 5-14 year olds were 0.6 and 0.1 per 1000 male population, respectively. There was a statistically significant decreasing temporal trend for the corrective procedure in cryptorchidism of 0.1 per 1000 male population aged under 5 years per annum (95% confidence interval: -0.01 to -0.05, p<0.001), but no temporal change for the corrective procedure in hypospadias (p = 0.60). CONCLUSION: HES data were of high quality for the study period. There was no significant change in the prevalence of surgically corrected hypospadias. However, there was an apparent decline in the prevalence of surgically corrected cryptorchidism that may reflect a decrease in the prevalence of the condition or may be due to a decrease in the rate of surgical intervention.

Incidence and survival of childhood Langerhans cell histiocytosis in Northwest England from 1954 to 1998.

BACKGROUND: Langerhans cell histiocytosis (LCH) is a rare proliferative disorder of pathological Langerhans cells, for which the aetiology and pathogenesis remain largely unknown. PROCEDURE: Information on the 101 children with LCH registered with the population-based Manchester Children's Tumour Registry (MCTR) between 1954 and 1998 was extracted from the records of the MCTR. This included age, sex, date of diagnosis, systems affected at diagnosis and follow-up. RESULTS: The overall incidence rate for LCH was 2.6 cases per million child years. In those under 1 year of age the incidence rate was 9.0 cases per million child years, compared to 0.7 cases per million in those aged 10-14 years (P < 0.0001 for age trend). There was no evidence of seasonal variation in presentation by month of birth or first symptom. Bone was the most common site of disease involvement (67% of cases), followed by skin (37%) and soft tissue (22%). The overall survival rate has improved over time, from 57% in 1954-1968 to 74% in 1985-1998. Ninety percent of deaths were due to disease progression, the remainder were due to complications of intensive therapy. The site of LCH lesions and extent of disease present at diagnosis strongly predicted survival outcome. Patients with initial liver involvement had a 5-year survival rate of 25% compared with 93% for those with bone lesions alone at diagnosis. CONCLUSIONS: Incidence rates varied significantly by age at diagnosis, and have been stable over time. Survival has improved considerably over time, but varies strongly by age and systems affected at diagnosis.

Space-time clustering of glioma cannot be attributed to specific histological subgroups.

We previously showed that infectious exposures may be involved in the aetiology of adult glioma, by analysing for space-time clustering using population-based data from the South of the Netherlands. Here we extended these analyses and describe in detail the space-time clustering patterns in glioma subgroups, gender and age-categories. Knox tests for space-time interactions between cases were applied with fixed thresholds of close in space, <5 km, and close in time, <1 year apart. We used the spatial coordinates of the addresses at diagnosis in the analyses. Tests were repeated replacing geographical distance with distance to the Nth nearest neighbour. N was chosen such that the mean distance was 5 km. Data were also analysed by a second order procedure based on K-functions. There was only statistically significant space-time clustering for oligodendroglioma. Clustering was present for adults aged 30-54 years and was more pronounced among males. Given the low prior probability of an infectious aetiology for this specific subgroup, these results should probably be interpreted as false-positive. We conclude that space-time clustering of glioma cannot be attributed to a specific glioma subgroup. The observed clustering in our previous study is therefore probably an overall effect within and between glioma subgroups.

Space-time clustering analyses of testicular cancer amongst 15-24-year-olds in Northern England.

There has been speculation that environmental exposures may be involved in the aetiology of testicular cancer in adolescent boys and young men. Indirect evidence for this hypothesis would be provided by the finding of space-time clustering. To examine this we have looked for evidence of space-time clustering using data from a population-based cancer registry from Northern England. All cases of testicular cancer diagnosed in males aged 15-24 years during the period 1968-2002 were included in the study. Tests for space-time interactions between cases were applied with fixed thresholds of close in space and close in time. Addresses at birth and diagnosis were used in the analyses. To adjust for the effect of varying population density tests were repeated replacing fixed geographical distances with nearest neighbour thresholds. A total of 257 cases of testicular cancer were identified for analysis. Overall there was no evidence for space-time clustering. However, there was statistically significant space-time clustering for 15-19-year-old based on time of birth and place of diagnosis (p<0.001). The very limited finding of space-time clustering may provide tentative evidence for an environmental, or infectious component to aetiology. However, it may well be a chance finding. A larger study based on national data is required.

Space-time clustering analyses of type 1 diabetes among 0- to 29-year-olds in Yorkshire, UK.

AIMS/HYPOTHESIS: Infections have been suggested to play a role in the aetiology of type 1 diabetes. The presence of space-time clustering is consistent with the notion of an environmental component in disease aetiology, possibly linked to infections. We tested for evidence of space-time clustering among children and young adults under 30 years of age using data from a population-based register in Yorkshire, UK. SUBJECTS AND METHODS: Two data sets of children and young people diagnosed with type 1 diabetes were analysed: (1) children aged 0-14 years and resident in Yorkshire during 1978-2002; (2) those aged 15-29 years and resident in West Yorkshire during 1991-2002. Tests for space-time interactions between cases were applied. Addresses at diagnosis were geo-coded and used as the basis for the analyses. RESULTS: The study analysed 3,019 type 1 diabetic patients in the 0-14 years age group and 989 patients in the 15-29 years group. Statistically significant space-time clustering based on place and time of diagnosis was detected both for the 10-14-year-olds (p=0.04) and for the 15-19-year-olds (p=0.01). CONCLUSIONS/INTERPRETATION: Previous studies of clustering of type 1 diabetes have generally been restricted to childhood. Our results from a data set that includes teenagers and young adults show that space-time clustering was limited to young people aged 10-19 years. This finding is consistent with an aetiology involving late exposure to infection. However, the question of whether this is directly diabetogenic or unmasks latent diabetes cannot be addressed by this methodology.

Space-time clustering patterns of gliomas in The Netherlands suggest an infectious aetiology.

To test the hypothesis that infectious exposures may be involved in glioma aetiology, we have analysed space-time clustering and seasonal variation using population-based data from the South of The Netherlands between 1983 and 2001. Knox tests for space-time interactions between cases were applied, with spatial coordinates of the addresses at time of diagnosis, and with distance to the Nth nearest neighbour. Data were also analysed by a second order procedure based on K-functions. Tests for heterogeneity and Edwards' test for sinusoidal variation were applied to examine seasonal variation of incidence. There was statistically significant space-time clustering in the Eastern, but not in the Western part of the region. Clustering was only present in adults, particularly in less densely populated areas. There was no evidence for seasonal variation. The results support a role for infectious exposures in glioma aetiology that may act preferentially in certain geographical areas.