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Previous studies have found marked increases in melanoma incidence. The increase among young people in northern England was especially apparent among females. However, overall 5-year survival has greatly improved. The present study aimed to determine whether socioeconomic factors may be involved in both etiology and survival. All 224 cases of malignant melanoma diagnosed in patients aged 10-24 years during 1968-2003 were extracted from a specialist population-based regional registry. Negative binomial regression was used to examine the relationship between incidence and area-based measures of socioeconomic deprivation and small-area population density. Cox regression was used to analyze the relationship between survival and deprivation and population density. There was significantly decreased risk associated with living in areas of higher unemployment (relative risk per 1% increase in unemployment=0.93; 95% confidence interval (CI) 0.90-0.96, P<0.001). Survival was better in less deprived areas (hazard ratio (HR) per tertile of household overcrowding=1.52; 95% CI 1.05-2.20; P=0.026), but this effect was reduced in the period 1986-2003 (HR=0.61; 95% CI 0.40-0.92; P=0.018). This study found that increased risk of melanoma was linked with some aspects of greater affluence. In contrast, worse survival was associated with living in a more deprived area. [ABSTRACT FROM AUTHOR]

Background and study aims: Adenoma detection is a key objective of colonoscopy, particularly in the context of colorectal cancer screening. The aim of this observational study was to identify the technical colonoscopy factors associated with adenoma detection. Patients and methods: The study analyzed data from the English Bowel Cancer Screening Programme. The indication for all colonoscopies was a positive fecal occult blood test. The relationships between the following colonoscopy factors and adenoma detection (one or more adenomas, advanced adenomas, right-sided adenomas, and total number of adenomas) were examined in multivariable analyses: bowel preparation quality, cecal intubation, withdrawal time, rectal retroversion, colonoscopist experience, antispasmodic use, sedation use, and start time of procedure. The following patient factors were controlled for: age, sex, body mass index, smoking, alcohol, deprivation, and geographical location. Results: A total of 31088 colonoscopies were analyzed. The following technical factors increased the relative risk of adenoma detection (P<0.001 in multivariable analysis unless otherwise stated): cecal intubation, increased withdrawal time, higher quality bowel preparation, intravenous antispasmodic use, earlier procedure start time within a session (P=0.018), and greater colonoscopist experience. Detection of advanced and right-sided adenomas also increased with these factors. Adenoma detection did not differ between sedated and unsedated colonoscopy (P= 0.143). Conclusion: This study demonstrated important associations between colonoscopy practice and adenoma detection. Use of intravenous antispasmodic was associated with increased adenoma detection. The effect of the start time of colonoscopy suggests that endoscopist fatigue may have a deleterious impact on adenoma detection. [ABSTRACT FROM AUTHOR]

Background: Artificial fluoridation of drinking water to improve dental health has long been a topic of controversy. Opponents of this public health measure have cited the possibility of bone cancer induction. The study objective was to examine whether increased risk of primary bone cancer was associated with living in areas with higher concentrations of fluoride in drinking water.Methods: Case data on osteosarcoma and Ewing sarcoma, diagnosed at ages 0-49 years in Great Britain (GB) (defined here as England, Scotland and Wales) during the period 1980-2005, were obtained from population-based cancer registries. Data on fluoride levels in drinking water in England and Wales were accessed through regional water companies and the Drinking Water Inspectorate. Scottish Water provided data for Scotland. Negative binomial regression was used to examine the relationship between incidence rates and level of fluoride in drinking water at small area level.Results: The study analysed 2566 osteosarcoma and 1650 Ewing sarcoma cases. There was no evidence of an association between osteosarcoma risk and fluoride in drinking water [relative risk (RR) per one part per million increase in the level of fluoride = 1·001; 90% confidence interval (CI) 0·871, 1·151] and similarly there was no association for Ewing sarcoma (RR = 0·929; 90% CI 0·773, 1·115).Conclusions: The findings from this study provide no evidence that higher levels of fluoride (whether natural or artificial) in drinking water in GB lead to greater risk of either osteosarcoma or Ewing sarcoma. [ABSTRACT FROM AUTHOR]

Background: There is a paucity of recent epidemiological data on bone cancers. The aim of this study was to describe incidence and survival patterns for bone cancers diagnosed during 1981 - 2002. Methods: Cases aged 0 - 39 years (236 osteosarcomas, 166 Ewing sarcomas and 73 chondrosarcomas) were analysed using Poisson and Cox regressions. Results: Incidence rates (per million persons per year) for osteosarcoma were 2.5 at age 0 - 14 years; 4.5 at age 15 - 29 years and 1.0 at age 30 - 39 years. Similarly, for Ewing sarcoma the incidence rates were 2.2; 2.9; 0.4 and for chondrosarcoma rates were 0.1; 1.2; 1.8 respectively. Incidence of osteosarcoma increased at an average annual rate of 2.5% (95% CI 0.4 - 4.7; P = 0.02), but there was no change in incidence of Ewing sarcoma or chondrosarcoma. There was a marginally statistically significant improvement in survival for Ewing sarcoma (hazard ratio (HR) per annum = 0.97; 95% CI 0.94 - 1.00; P = 0.06), although patients aged 15 - 39 years (n = 93) had worse overall survival than those aged 0 - 14 (n = 73; HR = 1.46; 95% CI 0.98 - 2.17; P = 0.06). There was no significant improvement in osteosarcoma survival (HR per annum = 0.98; 95% CI 0.95 - 1.01; P = 0.18). Conclusions: Reasons for poorer survival in Ewing sarcoma patients aged 15 - 39 years and failure to significantly improve survival for osteosarcoma patients requires further investigation. [ABSTRACT FROM AUTHOR]

Background: The aetiology of type 1 diabetes in children is uncertain. A number of recent studies have suggested an infectious aetiology. It has been postulated that an infectious agent may be involved. Support for this hypothesis may be provided by a finding of space-time clustering. The aims of this study were: (i) to determine whether there was space-time clustering in cases of childhood diabetes from north-east England; and to test for differences in space-time clustering: (ii) due to age at diagnosis; (iii) between the sexes and (iv) between levels of residential population density. Methods: We studied incidence of type 1 diabetes diagnosed in children aged 0-14 years and diagnosed during the period 1990-2007. All cases were resident in a defined geographical region of north-east England (Northumberland, Newcastle upon Tyne and North Tyneside). We applied a second-order procedure based on K-functions to test for global clustering. Locations were residential addresses at time of diagnosis. Tests were repeated using nearest neighbour thresholds to allow for variable population density, providing the primary result for each analysis. Differences between sexes and between levels of population density were assessed. Results: We analysed 457 cases of type 1 diabetes. Overall, there was marginally significant evidence of global space-time clustering (P = 0.089). There was statistically significant clustering amongst pairs of cases that contained at least one female (P = 0.017), but not amongst pairs of cases that contained at least one male (P = 0.190). Furthermore, there was significant clustering amongst pairs of cases that contained at least one from a more densely populated area (P = 0.044), but not amongst pairs of cases that contained at least one from a less densely populated area (P = 0.226). Conclusion: Although the analyses have only found marginally significant evidence of global spacetime clustering for cases of type 1 diabetes diagnosed in north-east England, there were two notable findings. First, there was evidence of clustering amongst females and secondly clustering was confined to cases from more densely populated areas. These findings are consistent with a possible aetiological involvement of an infectious agent. [ABSTRACT FROM AUTHOR]

Background: This study examined sex-specific patterns and temporal trends in the incidence of solid tumours in the Northern Region of England from 1968 to 2005. This updates earlier analyses from the region where sex was not considered in depth. Sex-specific analyses were carried out to determine whether sex differences might provide clues to aetiology. Methods: Details of 3576 cases, aged 0-24 years, were obtained from a specialist population-based cancer registry. There were 1843 males (886 aged 0-14 years and 957 aged 15-24 years) and 1733 females (791 aged 0-14 years and 942 aged 15-24 years). Age-standardized incidence rates (per million population) were calculated. Linear regression was used to analyze temporal trends in incidence and annual percentage changes were estimated. Analyses were stratified by sex and by age-group. Results: There were marked differences in incidence patterns and trends between males and females and also between age-groups. For males central nervous system (CNS) tumours formed the largest proportion of under- 15 cases and germ cell tumours was the largest group in the 15-24's, whilst for females CNS tumours dominated in the under-15's and carcinomas in the older group. For 0-14 year olds there were male-specific increases in the incidence of rhabdomyosarcoma (2.4% per annum; 95% CI: 0.2%-4.5%) and non-melanotic skin cancer (9.6%; 95% CI: 0.0%-19.2%) and female-specific increases for sympathetic nervous system tumours (2.2%; 95% CI: 0.4%-3.9%), gonadal germ cell tumours (8.6%; 95% CI: 4.3%-12.9%) and non-gonadal germ cell tumours (5.4%; 95% CI: 2.8%-7.9%). For 15-24 year olds, there were male-specific increases in gonadal germ cell tumours (1.9%; 95% CI: 0.3%-3.4%), non-gonadal germ cell tumours (4.4%; 95% CI: 1.1%-7.7%) and non-melanotic skin cancer (4.7%; 95% CI: 0.5%-8.9%) and female-specific increases for osteosarcoma (3.5%; 95% CI: 0.5%-6.5%), thyroid cancer (2.8%; 95% CI: 0.1%-5.6%) and melanoma (4.6%; 95% CI: 2.2%-7.1%). Conclusion: This study has highlighted notable differences between the sexes in incidence patterns and trends for solid tumours. Some of these sex-specific differences could have been obscured if males and females had been analysed together. Furthermore, they suggest aetiological differences or differential susceptibility to environmental factors between males and females. [ABSTRACT FROM AUTHOR]

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<0.00), 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. [ABSTRACT FROM AUTHOR]

Background: We specifically tested the aetiological hypothesis that a factor influencing geographical or temporal heterogeneity of childhood central nervous system (CNS) tumour incidence was related to exposure to a transient environmental agent.Methods: Information was extracted on individuals aged 0-14 years, diagnosed with a CNS tumour between the 1st January 1974 and 31st December 2006 from the Yorkshire Specialist Register of Cancer in Children and Young People. Ordnance Survey eight-digit grid references were allocated to each case with respect to addresses at the time of birth and the time of diagnosis, locating each address to within 0.1 km. The following diagnostic groups were specified a priori for analysis: ependymoma; astrocytoma; primitive neuroectodermal tumours (PNETs); other gliomas; total CNS tumours. We applied the K-function method for testing global space-time clustering using fixed geographical distance thresholds. Tests were repeated using variable nearest neighbour (NN) thresholds.Results: There was statistically significant global space-time clustering for PNETs only, based on time and place of diagnosis (P = 0.03 and 0.01 using the fixed geographical distance and the variable NN threshold versions of the K-function method respectively).Conclusions: There was some evidence for a transient environmental component to the aetiology of PNETs. However, a possible role for chance cannot be excluded. [ABSTRACT FROM AUTHOR]

Hungary has had one of the highest suicide mortality rates in the world for decades. Investigating seasonality of suicide deaths is essential as its findings could be key elements in the prevention. In our study we have analyzed the seasonal effect in suicide mortality in relation to possible risk factors in Hungary during 1995-2017. Data on the numbers of suicide deaths were obtained from a published online database. Negative binomial regression was employed to investigate the effect of possible risk factors and seasonal and annual trends in suicide rates. The seasonal effect was further investigated, adding a significant risk factor from the "initial" negative binomial regression. The suicide risk was significantly ( p  < 0.001) higher in men than in women (incidence rate ratio: 3.48), and it increased with age and decreased with education level. Marriage was a protective factor against suicide. Annual suicide mortality declined significantly ( p  < 0.001 for trend) from 36.7 (95% confidence interval: 35.5-37.9) to 16.5 (15.7-17.3) per 100,000 persons per year during the study period. Significant seasonality was found in suicide rates with a peak in late June. Similar peaks were observed at each level of each risk factor. There were differences in peaks by suicide method. The peak of non-violent suicides was in early June; suicides committed by violent methods peaked half a month later. This study suggests that there was a significant seasonal effect on suicide deaths between 1995 and 2017, which remained significant even in the presence of each risk factor. To our knowledge, this has been the first study to investigate the seasonal pattern so extensively in Hungary. Our findings confirm that the environmental effects are involved in the etiology of suicide mortality., Competing Interests: none., (© 2021 The Authors. Published by Elsevier Ltd.)

Introduction: Childhood brain tumours (CBTs) are the second most common type of cancer in individuals aged 0-24 years globally and cause significant morbidity and mortality. CBT aetiology remains poorly understood, however previous studies found higher CBT incidence in high-income countries (HIC) compared to low-middle income countries (LMIC), suggesting a positive relationship between incidence and wealth., Materials & Methods: Aggregated data from Cancer Incidence in Five Continents (CI5) were used to explore CBT epidemiology. Incidence rate ratios (IRR) compared CBT rates between twenty-five geographically and economically diverse countries. The relationship between incidence and economic development was explored using linear regression models and Spearman's rank correlation tests. Trends in CBT incidence between 1978 and 2012 were investigated using average annual percentage changes (AAPC)., Results: CBT incidence was highest in North America and lowest in Africa. CBT incidence rates increased significantly with increasing GDP per capita (p = 0.006). Gini index was significantly negatively associated with CBT incidence. Incidence decreased with increasing income inequality within countries, indicated by higher Gini indices (p = 0.040). Increasing and decreasing CBT incidence trends were observed within individual countries, although only Italy (p = 0.02) and New Zealand (p < 0.005) experienced statistically significant changes over time., Conclusions: The excess disease found in HIC may be explained by environmental risk factor exposure increasing CBT risk in wealthy populations. However, systematic limitations of substandard cancer detection and reporting in LMIC may mean incidence disparities result from misinformation bias rather than genuine differences in risk factor exposure. Further research is required to comprehensively describe CBT epidemiology and explain study findings., (Crown Copyright © 2021. Published by Elsevier Ltd. All rights reserved.)

Background: The etiology of most cases of congenital hypothyroidism (CHT) due to thyroid dysgenesis (DG) is unknown. If transient environmental factors can impact on thyroid gland development, then clustering of cases in time and/or space may occur, and this would be more likely in thyroid DG than dyshormonogenesis (DHG). Methods: The newborn screening program for CHT in Scotland is linked to a central database that includes case details such as postcode. The etiology of CHT is investigated in many cases of CHT using scintigraphy and/or ultrasonography. We looked for evidence of a change in CHT incidence with year of birth and according to season of the year. We then undertook space-time clustering analysis (using a method based on K -functions, with nearest neighbor thresholds) of CHT in Scotland between 1979 and 2015. We also looked for evidence of overall changes associated with sex and area-based birth density. Results: Of 531 cases with CHT during the study period, 290 cases had been categorized as DG ( n  = 229) or DHG ( n  = 61) following more detailed investigation. The incidence of CHT increased with year of birth and was in part linked to changing methodology, but there was no seasonality. There was no evidence of overall space-time clustering ( p  = 0.06), but there was evidence of clustering in babies with DG ( p  = 0.007). This picture appeared to be most closely linked to underlying thyroid gland hypoplasia rather than thyroid gland agenesis or ectopia. There was significant space-time clustering for both males and females, but clustering was restricted to lesser birth density areas. There was also evidence of clustering for unknown cases ( p  < 0.001). Clustering of these cases was restricted to females but was present for cases from both greater and lesser birth density areas. There was no evidence of clustering in cases of DHG. Conclusions: These data suggest that an unidentified environmental factor or factors may be involved in the etiology of thyroid DG in Scotland. The variation in CHT incidence observed internationally may reflect environmental as well as genetic factors.

Background: The incidence of cutaneous malignant melanoma, which is mostly attributable (86%) to UV radiation exposure, has been steadily increasing over the past four decades in predominantly fair-skinned populations. Although public health campaigns are increasing sun-protective behaviour in England, their effect on melanoma incidence is largely unknown. We conducted a retrospective population-based cohort study to examine whether there have been changes in the epidemiology of melanoma in England during the past four decades., Methods: Individual level data for patients diagnosed with melanoma in England during 1981-2018 were obtained from the Office for National Statistics/Public Health England. Average annual incidence rates were calculated by three age categories (0-34, 35-64, 65+ years), gender and anatomical site during the seven five-year time periods (1981-85 to 2011-15) and the recent three-year period (2016-18). The percentage change in incidence was calculated as change in the average incidence rate from the first (1981-85) to the last time period (2016-18). The Average Annual Percentage Change (AAPC) was estimated using the slope of the linear trend line fitted to the incidence rates by year of diagnosis., Findings: During the 38-year period (1981-2018), a total of 265,302 cases of melanoma (45.7% males, 54.3% females) were registered in England. The average annual number of cases increased from 837/year in 1981-85 to 6963/year in 2016-18 in males (+732%), and from 1609/year in 1981-85 to 6952/year in 2016-18 in females (+332%). In the young age-group (0-34 years), the average annual incidence rates initially increased from 1981-85 to 2001-05 and then stabilised during the recent period (2006-18). In the middle age group (35-64 years), the rates increased by +332% (AAPC, 10.4%) in males (from 5.6/100,000 in 1981-85 to 24.2/100,000 in 2016-18) and +185% (AAPC, 5.7%) in females (from 10.2/100,000 in 1981-85 to 29.1/100,000 in 2016-18); and in the old age-group (65+ years) the rates increased by +842% (AAPC, 25.7%) in males (from 9.6/100,000 in 1981-85 to 90.4/100,000 in 2016-18) and +381% (AAPC, 11.2%) in females (from 12.5/100,000 in 1981-85 to 60.1/100,000 in 2016-18). The largest increase in incidence in both males and females was observed for melanoma of the trunk (+817%, AAPC, 24.8% in males and +613%, AAPC, 18.3% in females), followed by melanoma of upper limb (+750%, AAPC, 22.9% in males and 518%, AAPC, 15.5% in females)., Interpretation: It appears that the incidence of melanoma among young people in England has stabilised (or levelled off) in recent decades, whereas it continues to increase substantially in older population. These findings suggest that public health campaigns targeted at children/adolescents/parents may be favourably influencing melanoma incidence. The steeper increase in incidence in males is consistent with their relatively greater sun exposure and poor sun-protective behaviour. All the available evidence suggests that the enormous increase in the melanoma of the trunk and upper limb, since the 1980s, is most likely due to increasing trend in intermittent high intensity recreational UV radiation exposure (e.g. sunbathing, holidaying in places with strong sunlight, indoor tanning)., Funding: This work was supported by Brighton and Sussex Medical School (BSMS)., Competing Interests: The authors declare no conflict of interest., (© 2021 The Author(s).)

The Mr F study investigates the pathogenesis of low trauma distal forearm fractures in men and includes volumetric bone mineral density (vBMD) measurements at the ultradistal forearm as there are no current data. A standard 64 slice CT scanner was used to determine if it was possible to adapt the existing Mindways quantitative computed tomography Pro software for measuring vBMD values at the hip and spine sites. For calculation of intra- and interobserver reliability 40 forearm scans out of the 300 available were chosen randomly. The images were analyzed using the Slice Pick module and Bone Investigational Toolkit. The 4% length of the radius was chosen by measuring the length of the radius from the scaphoid fossa distally to the radial head. The acquired image then underwent extraction, isolation, rotation, and selection of region of interest in order to generate a report on vBMD. A cross-sectional image was created to allow the generation of data on the cortical and trabecular components separately. Repeat analyses were undertaken by 3 independent observers who were blinded as to whether the image was from a participant with or without fracture. The images were presented in random order at each time point. The following parameters were recorded: cortical cross sectional area, total vBMD, trabecular vBMD, and cortical vBMD (CvBMD). Data were analyzed by calculating intraclass correlation coefficients for intra- and interobserver reliability. The lowest values occurred at the CvBMD with intraobserver reliability of 0.92 (95% confidence interval [CI] of 0.86-0.96) and interobserver reliability of 0.92 (95% CI 0.89-0.96). All other parameters had reliability values between 0.97 and 0.99 with tighter 95% CI than for CvBMD. The method of adapting the Mindways Pro software using a standard CT to produce vBMD and structural data at the ultradistal radius is reliable., (Copyright © 2019 The International Society for Clinical Densitometry. Published by Elsevier Inc. All rights reserved.)

Background: Despite aggressive multimodal therapy, >50% of children with high-risk neuroblastoma (HRNB) relapse. Survival after relapse is rare, and no consensus currently exists on the most effective therapy., Objective: To conduct a systematic review of the literature on effectiveness of re-induction chemotherapy in children with relapsed HRNB., Methods: Database searches were performed to identify studies looking at response to 1st line chemotherapy for children >12 months at diagnosis with first relapse of HRNB. Studies not reporting separate outcomes for HRNB patients or of refractory patients only were excluded. Two independent reviewers extracted the data and assessed study quality using a modified Newcastle-Ottawa tool., Results: Nine studies were identified fitting the inclusion criteria. All except one were single arm cohorts, and two were retrospective database reviews from single centres. One was a multicentre randomised controlled trial. All used a version of the validated International Neuroblastoma Response Criteria with 8 recording best ever response and 1 at a specified time, and 5 had central review. The proportion of relapsed patients varied from 24 to 100% with 30-93% receiving upfront myeloablative therapy. The response rate varied from 6 to 64%; however, because of heterogeneity, studies were not directly comparable, and no single treatment emerged as the most effective re-induction therapy., Conclusions: To date, there is no clear superior re-induction therapy for 1st relapse of HRNB. Randomised controlled trials with separate arms for relapsed versus refractory disease are needed to determine optimal re-induction chemotherapy to act as a backbone for testing newer targeted agents., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Older people with delirium occupy more than one third of acute medical beds and require increased medical attention, as care at present is suboptimal. In addition, since delirium is undetected, it should form a target for teaching in wards. Moreover, as people with delirium are largely dependent on daily interactions and care by inpatients professional staff, it is important to address stigmatisation of these vulnerable patients. This is especially important as previous studies have shown that negative staff attitudes towards these patients undermine good care. This single center cross-sectional study was designed to determine the extent of institutional stigma among health professionals involved in the care of people with delirium. For this, professional staff working on medical wards and in communities were approached to fill in a questionnaire containing the adapted Delirium Stigma Scale and the EuroQol five dimensions (EQ-5D-5L) questionnaire. Additional demographic information concerning their education and professional and personal experience with delirium was also collected. The characteristics associated with stigma were determined from the sample. The findings of our study provide an insight into the high level of stigmatisation of delirium patients among professionals (mean 11.66/18 points). This was not related to professionals' own experiences of delirium, their educational and professional backgrounds, or them having received formal delirium education. However, working closely with people with delirium seems to have a positive impact on the de-stigmatisation of this population among health professionals. Our findings that attitudes are not influenced by formal delirium teaching need to be incorporated into the design of interprofessional educational interventions. Accordingly, we advocate more direct patient-oriented and care delivered teaching interventions.

Background: Studies have shown marked improvements in survival between 1981 and 2000 for Ewing sarcoma patients but not for osteosarcoma. This study aimed to explore socio-economic patterning in early mortality rates for both tumours., Procedure: The study analysed all 2432 osteosarcoma and 1619 Ewing sarcoma cases, aged 0-49 years, diagnosed in Great Britain 1985-2008 and followed to 31/12/2009. Logistic regression models were used to calculate risk of dying within three months, six months, one year, three years and five years after diagnosis. Associations with Townsend deprivation score and its components were examined at small-area level. Urban/rural status was studied at larger regional level., Results: For osteosarcoma, after age adjustment, mortality at three months, six months and one year was associated with higher area unemployment, OR = 1.05 (95% CI 1.00, 1.10), OR = 1.04 (95% CI 1.01, 1.08) and OR = 1.04 (95% CI 1.02, 1.06) respectively per 1% increase in unemployment. Mortality at six months was associated with greater household non-car ownership, OR = 1.02 (95% CI 1.00, 1.03). For Ewing sarcoma, there were no significant associations between mortality and overall Townsend score, nor its components for any time period. For both tumours increasing mortality was associated with less urban and more remote rural areas., Conclusions: This study found that for osteosarcoma, early mortality was associated with residence at diagnosis in areas of higher unemployment, suggesting risk of early death may be socio-economically determined. For both tumours, distance from urban centres may lead to greater risk of early death., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Despite strong evidence of a social gradient in cancer survival among UK adults, studies in children and young people remain inconclusive and have not included renal tumours. This study investigated the relationship between socioeconomic status and survival from renal tumours among children and young people., Procedure: Kaplan-Meier estimation and Cox regression were used to analyse survival for all 209 renal tumours in children and young people (0-24 years) diagnosed 1968-2012 and registered by a specialist population-based registry. Sociodemographic and clinicopathologic variables, including paternal occupation at birth, were also analysed., Results: No significant disparity in overall renal tumour and Wilms tumour (WT) survival was observed according to paternal social class [p=0.988 and 0.808, respectively]. The strongest predictor of survival was stage, with late stage (III-IV) disease having a 4-fold higher risk of death compared to early stage (I-II) disease [p<0.001]. Similarly, high mortality-risk was seen for late stage WT in children aged 0-14 years (Hazard Ratio=6.37; 95% CI=2.60-15.59)., Conclusions: This study did not detect a significant social gradient in renal tumour survival. The identification of tumour stage as a strong predictor of survival irrespective of age, necessitates the development of appropriate public health interventions that target early diagnosis and treatment., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Previously excesses in incident cases of leukaemia and non-Hodgkin lymphoma have been observed amongst young people born or resident in Seascale, Cumbria. These excesses have not been seen more recently. It is postulated that the former apparent increased risk was related to 'unusual population mixing', which is not present in recent years. This study investigated changes in measures of population mixing from 1951-2001. Comparisons were made between three specified areas. Area-based measures were calculated (migration, commuting, deprivation, population density). All areas have become more affluent, although Seascale was consistently the most affluent. Seascale has become less densely populated, with less migration into the ward and less diversity with respect to migrants' origin. There have been marked changes in patterns of population mixing throughout Cumbria. Lesser population mixing has been observed in Seascale in recent decades. Changes in pattern and nature of population mixing may explain the lack of recent excesses., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Article Title and Bibliographic Information: Community water fluoridation and health outcomes in England: a cross-sectional study. Young N, Newton J, Morris J, Morris J, Langford J, Iloya J, Edwards D, Makhani S, Verne J. Community Dent Oral Epidemiol 2015; 43:550-9., Source of Funding: Public Health England TYPE OF STUDY/DESIGN: Ecological (area based)., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Purpose: Most people with epilepsy (PWE) in low-income countries are not treated. We identified risk factors for the epilepsy treatment gap in rural Tanzania., Methods: We identified adult PWE in a community-based prevalence study. Factors associated with failure to access or default from medical care were identified using logistic regression modelling., Results: A total of 291 PWE were included, of whom 253 (86.9%) had presented to medical services. Failure to present was positively associated with using alcohol (odds ratio (OR) 4.20; 95% confidence interval (CI) 1.63 to 10.82) or attending traditional healers (OR 2.62; CI 1.00 to 6.83) and inversely associated with having completed primary education (OR 0.33; CI 0.11 to 0.96). Default from treatment was associated with being male (OR 3.35; CI 1.39 to 8.09), having a seizure-related injury (OR 2.64; CI 1.12 to 6.19), believing in a supernatural cause for epilepsy (OR 5.44; CI 1.48 to 19.94) or having no expressed knowledge of cause (OR 5.29; CI 1.60 to 17.52). Cases less likely to default had a duration of epilepsy greater than 10 years (OR 0.28; CI 0.09 to 0.90) or had previously received a seizure-related diagnosis (OR 0.25; CI 0.09 to 0.65). Of all 291 PWE included, 118 denied taking AEDs; the epilepsy treatment gap in this population was therefore 40.5% (95% CI 34.9 to 46.2)., Conclusion: Interventions to improve access to education and to support formal diagnoses may promote access to, and retention under, medical care for PWE in rural Tanzania and in other low-income countries., (Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.)

Purpose: Previous research from developed countries has shown a marked increase in the incidence of testicular cancer in the past 50 years. This has also been demonstrated in northern England, along with improving 5-year survival. The present study aims to determine if socioeconomic factors may play a role in both etiology and survival from non-seminoma testicular cancer., Materials and Methods: We extracted all 214 cases of non-seminoma testicular cancer diagnosed in teenage and young adult men aged between 15 and 24 years during 1968 to 2006 from the Northern Region Young Persons' Malignant Disease Registry, which is a population-based specialist regional registry. Negative binomial regression was used to examine the relationship between incidence and both the Townsend deprivation score (and component variables) and small-area population density. Cox regression was used to analyze the relationship between survival and both deprivation and population density., Results: Decreased incidence was associated with living in areas of higher household overcrowding for young adults aged between 20 and 24 years (relative risk per 1% increase in household overcrowding = 0.79; 95% CI: 0.66-0.94) but no association was detected for young people aged between 15 and 19 years. Community-level household unemployment was associated with worse survival (hazard ratio per 1% increase in household unemployment = 1.04; 95% CI: 1.00-1.08)., Conclusions: This study has shown that increased risk of non-seminoma testicular cancer in teenage and young adult men may be associated with some aspect of more advantaged living. In contrast, greater deprivation is linked with worse survival prospects. The study was ecological by design and so these area-based results may not necessarily apply to individuals., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: This study investigated annual and seasonal trends in deaths for cancers of the female genital organs and breast in Hungary between 1979 and 2013., Study Design: Data on the numbers of cancer deaths were obtained from the published nationwide population register. Joinpoint regression was applied to investigate the yearly trends in cancer mortality rates. Cyclic trends were investigated using logistic regression, Edwards' and Walter-Elwood methods., Results: The majority of deaths from cancers of the female genital organs and breast occurred in winter but using the observed numbers of deaths a significant seasonal pattern was only revealed for deaths from breast cancer with a peak in January and a nadir in July. However, seasonality in the proportion of deaths from female genital organs and breast cancers out of deaths from all causes detected a different peak and nadir. The proportion of female genital organs and breast cancer deaths out of deaths from all causes was higher around the end of summer and significant seasonal variation with a peak in August and nadir in February was revealed., Conclusion: This Hungarian study suggests that there was a significant seasonal effect on female genital organs and breast cancer mortality. Both seasonal patterns are interesting and informative to potentiate prevention. Our findings suggest that infectious diseases may increase the risk of the mortality among the immune deficient patents., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

The aetiology of primary biliary cirrhosis (PBC) is not well established. Previously we found evidence of space-time clustering and seasonal variation in the date of diagnosis, suggesting a possible role for a transient or seasonally varying environmental factor. We examined whether a temporally varying environmental agent may be involved by analysing population-based PBC data from northeast England over 1987-2003. Using an adaptation of a method proposed by Potthoff and Whittinghill, we found significant temporal variation by date of diagnosis at the level of aggregation of one year. However, there was no evidence for general irregular (non-seasonal) temporal clustering within periods less than a year. These results provide little support for the involvement of agents occurring in geographically widespread mini-epidemics, but--taken together with studies of spatial and spatio-temporal clustering--do not preclude the role of more localised sporadic mini-epidemics. Future research should seek to elicit putative environmental agents., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Previously, we identified space-time clustering in certain childhood cancers. This study aimed to determine whether there was cross-space-time clustering between different diagnostic groups. A total of 32,295 cases were diagnosed during 1969-1993. Cross-space-time clustering was analyzed by a second-order procedure based on Diggle's method. Locations were birth and diagnosis addresses. The following space-time combinations were examined: address and date of birth; address at birth and date of diagnosis; address and date of diagnosis. Cross-space-time clustering analyses considered clustering pairs of cases from two different diagnostic groups. Formal statistical significance was taken as p < 0.00067 and marginal significance 0.01 > p ≥ 0.00067. Based on address at birth and date of diagnosis, there was statistically significant cross-clustering between cases of HL and intracranial and intraspinal embryonal tumors (IIET), both aged 0-14 years (p < 0.0001). Based on address and date of birth, there was marginally significant cross-clustering between cases of lymphoid leukemia (LL) aged 5-14 years and Hodgkin lymphoma (HL) aged 0-14 years (p = 0.0019). Based on address and date of diagnosis there was marginally significant cross-clustering between cases of LL aged 1-4 years and soft tissue sarcoma (STS) aged 0-14 years (p = 0.0041). Findings from this study are consistent with possible common aetiological factors between different diagnostic groups. They suggest a common aetiology for the following pairs of diagnostic groups: HL and IIET; older cases of LL and HL; younger cases of LL and STS. The possibility of common infectious mechanisms should be explored., (© 2013 The Authors. Published by Wiley Periodicals, Inc. on behalf of UICC.)

We report a 16.5% increase in platelet immunoglobulin (Ig) content in subjects with Alzheimer's disease (AD) in relation to cognitively intact individuals (p = 0.021), whereas the plasma Ig levels were unaltered (p = 0.428). The upregulation of platelet Ig was not explained by age, duration of dementia, or degree of cognitive impairment. However, AD subjects treated with cholinesterase inhibitors (n = 21) had lower levels of platelet Ig (p = 0.009) than AD subjects not treated with anti-dementia drugs (n = 4) and similar to those of control subjects (n = 24; p = 0.069). The anti-dementia treatment did not influence the plasma Ig levels (p = 0.177). These preliminary findings require further confirmation in studies on larger number of AD subjects with various stages of cognitive impairment, and who would be assessed prior to initiation of and during cholinesterase inhibitor treatment.

Objective: The NHS Bowel Cancer Screening Programme (BCSP) uses faecal occult blood (FOB) testing to select patients aged 60-69 years for colonoscopy., Aim: To examine the association between aspirin use and the detection of colorectal neoplasia in screened patients undergoing colonoscopy., Methods: Data were collected prospectively on individuals who underwent colonoscopy following a positive FOB test in the South of Tyne area between February 2007 and 2009. The relationship between the presence of colorectal neoplasia and age, gender, body mass index (BMI) and current aspirin use were evaluated using logistic regression analysis., Results: 701 individuals underwent colonoscopy. 414 (59.1%) were male and 358 (51.1%) aged over 65 years. Males had a higher incidence of colorectal neoplasia (relative risk 2.26, 95% CI 1.65-3.10, p < 0.001). Current aspirin use was associated with a lower neoplasia detection rate (relative risk 0.79, 95% CI 0.50-0.98, p = 0.039). Increased age and BMI were not significantly associated with higher neoplasia detection., Conclusion: Amongst individuals undergoing colonoscopy following a positive FOB test in the BCSP, current aspirin use was associated with a lower incidence of colorectal neoplasia. This may represent the chemopreventative effect of aspirin or increased false positivity of FOB testing. Further work is needed to clarify the contribution of each and could reduce the number of unnecessary colonoscopies., (Copyright © 2012 S. Karger AG, Basel.)

Unlabelled: The etiology of primary biliary cirrhosis (PBC) is far from clear. Both genetic and environmental factors are likely to be involved. We have previously reported evidence of space-time clustering, suggesting that a transient environmental agent may be involved in etiology. To further examine whether a seasonally varying environmental agent may contribute to the etiology of PBC, we have analyzed seasonal variation with respect to month of diagnosis using population-based data from northeast England over a defined period (1987-2003). Date of diagnosis was defined as the earliest date at which the patient was found to have fulfilled any two of three diagnostic criteria (i.e., antimitochondrial antibody-positive titer ≥1 in 40, cholestatic liver blood tests, diagnostic or compatible liver histology). Monthly expected (E) numbers of cases were calculated under an assumption of a uniform distribution throughout the year. Observed counts (O) were compared with the expected numbers. The chi-squared heterogeneity test was used to test for overall nonuniform variation and also for individual months. Poisson regression analysis was used to fit a sinusoidal (i.e., harmonic) model to the data, using month of diagnosis as a covariate in the model. There was a marked peak for diagnoses in the month of June (O = 115, E = 84.7, O/E = 1.36; P = 0.001). Furthermore, there was evidence of a sinusoidal pattern with a June peak (P = 0.012)., Conclusion: These highly novel results provide further evidence for the involvement of a seasonally varying environmental agent in the etiology of PBC., (Copyright © 2011 American Association for the Study of Liver Diseases.)

Evaluation of: Schmidt LS, Kamper-Jorgensen M, Schmeigelow K et al. Infectious exposure in the first years of life and risk of central nervous system tumours in children: analysis of birth order, childcare attendance and seasonality of birth. Br. J. Cancer 102(11), 1670-1675 (2010). Early infectious exposures have been implicated in the etiology of childhood CNS tumors. The article evaluated here assesses whether infectious exposure in the first years of life is involved by analyzing birth order, childcare attendance and seasonality of birth. The conclusion is that exposure to infectious disease in early childhood does not play an important role in the etiology of pediatric CNS tumors. It is noted that the measures used are only proxies for infectious exposures and, as such, may not accurately reflect the underlying infectious burden. Furthermore, this study is from the Nordic countries and from a later period than previous studies. Differences in patterns of exposure to infection may vary geographically between countries and may have changed over time. However, the authors have not excluded the possibility that a specific infectious agent is involved, and it is agreed here that future efforts should include a focus on a search for such an agent or agents, as well as formulating plausible, diagnostic-specific, mechanistic hypotheses.

Although the epidemiology of malignant bone tumours in children and young adults has been explored, no definitive causation of any specific tumour has yet been identified. We performed a literature review (1970-2008) to find all papers covering possible aetiological factors involved in the development of bone tumours in children and young adults. Several associations have been reported with some consistency: the presence of hernias and Ewing sarcoma; high fluoride exposure and osteosarcoma; and parental farming and residence on a farm, younger age at puberty and family history of cancer for all bone tumours, especially osteosarcoma. Clearly further research is needed to confirm or refute these putative risk factors. It is likely that studies of gene-environment interactions may prove to be the most fruitful of future research.

A previous study found a thyroid cancer excess in Cumbria following the Chernobyl explosion, but did not analyse sex-specific effects. This study examines sex differences in the incidence of thyroid cancer. Ninety-five primary thyroid carcinomas (69 females, 26 males) diagnosed in those aged 0-24 during 1968-2005 were identified from the Northern Region Young Persons' Malignant Disease Registry. Age-standardised incidence rates (ASRs), rate ratios (RRs) and 95% confidence intervals (CIs) were calculated. For males, the ASR was 0.6 per million person-years during the pre-Chernobyl period (1968-1986), and was 1.8 per million person-years during the post-Chernobyl period (1987-2005). For females, the ASR was 2.4 pre-Chernobyl and was 3.9 post-Chernobyl. The previously noted excess in Cumbria was entirely confined to females (Cumbrian females: RR for post-Chernobyl compared with pre-Chernobyl=10.8; 95% CI: 1.4-85.3). These findings may be consistent with sex-specific differences in susceptibility to an environmental exposure, such as fallout from the Chernobyl nuclear accident.

The aetiology of childhood cancer is poorly understood. Both genetic and environmental factors are likely to be involved. The presence of spatial clustering is indicative of a very localized environmental component to aetiology. Spatial clustering is present when there are a small number of areas with greatly increased incidence or a large number of areas with moderately increased incidence. To determine whether localized environmental factors may play a part in childhood cancer aetiology, we analyzed for spatial clustering using a large set of national population-based data from Great Britain diagnosed 1969-1993. The Potthoff-Whittinghill method was used to test for extra-Poisson variation (EPV). Thirty-two thousand three hundred and twenty-three cases were allocated to 10,444 wards using diagnosis addresses. Analyses showed statistically significant evidence of clustering for acute lymphoblastic leukaemia (ALL) over the whole age range (estimate of EPV = 0.05, p = 0.002) and for ages 1-4 years (estimate of EPV = 0.03, p = 0.015). Soft-tissue sarcoma (estimate of EPV = 0.03, p = 0.04) and Wilms tumours (estimate of EPV = 0.04, p = 0.007) also showed significant clustering. Clustering tended to persist across different time periods for cases of ALL (estimate of between-time period EPV = 0.04, p =0.003). In conclusion, we observed low level spatial clustering that is attributable to a limited number of cases. This suggests that environmental factors, which in some locations display localized clustering, may be important aetiological agents in these diseases. For ALL and soft tissue sarcoma, but not Wilms tumour, common infectious agents may be likely candidates.

Aim: We aimed to describe and contrast the epidemiology of haematological malignancies among 0-14 and 15-24-year-olds in northern England from 1990 to 2002 and compare clinical trial entry by age group., Patients and Methods: Incidence rates were examined by age, sex and period of diagnosis and differences were tested using Poisson regression. Differences and trends in survival were assessed using Cox regression., Results: 1680 subjects were included comprising 948 leukaemias and 732 lymphomas. Incidence rates for acute lymphoblastic leukaemia were significantly higher for 0-14 compared to 15-24-year-olds, whilst Hodgkin lymphoma showed the reverse. No significant changes in incidence were observed. 60% of leukaemia patients aged 15-24 years entered trials compared to 92% of 0-14-year-olds. Survival rates were significantly lower and improved less markedly over time for 15-24 compared to 0-14-year-olds, particularly for leukaemia., Conclusions: Trial accrual rates need to be improved amongst 15-24-year-olds and a more structured follow-up approach adopted for this unique population.

Previously, we identified space-time clustering in certain childhood cancers around diagnosis residence. These findings provided support for the involvement of environmental agents in etiological processes occurring close to diagnosis. We have reanalyzed the same British population-based dataset. The aim of the study was to determine whether there was space-time clustering around the residence at birth in relation to time of birth and separately from time of diagnosis. A total of 29,553 cases, diagnosed during the period 1969-1993, were examined by a second-order procedure based on K-functions. Locations were birth addresses, but separately, both dates of birth and diagnosis were analyzed. There was statistically significant space-time clustering for Hodgkin lymphoma (HL) and central nervous system (CNS) tumors (p=0.047 and 0.01, respectively, based on birth date) and for total leukemia at ages 1-4 years only, Non-Hodgkin lymphoma (NHL) and Wilms tumor (p=0.01, 0.02 and 0.006, respectively, based on diagnosis date). These results, interpreted together with other epidemiological evidence, suggest an etiological role for environmental factors focused around birth address for certain childhood cancers. For HL and CNS tumors, findings suggest that etiological exposures occurred at similar ages or in utero. For leukemia, NHL and Wilms tumor there is support for exposures occurring at similar times before diagnosis. For leukemia, HL, NHL and CNS tumors, but not Wilms tumor, the findings are consistent with infectious hypotheses., (Copyright (c) 2008 Wiley-Liss, Inc.)

Purpose: The etiology of congenital cerebral palsy is unclear. Recent studies have suggested that maternal infection is involved. Indirect, but supportive, evidence for an infectious hypothesis would be provided by the finding of space-time clustering., Methods: We analyzed all 906 cases born during the period 1991-2003 using a population-based registry from Northern England. We applied the K-function method for testing global space-time clustering and used residential addresses at the time of birth. The Knox method was used to determine the spatio-temporal range over which global clustering occurred. Tests were repeated using nearest neighbor thresholds to allow for variable population density. Additionally, Kulldorff's scan statistic identified specific space-time clusters., Results: There was statistically significant evidence of global space-time clustering (p