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Abstract Background The aetiology of bone cancers is poorly understood. This study examined geographical patterning in incidence of primary bone cancers diagnosed in 0–49 year olds in Great Britain during 1980–2005 to provide information on factors linked with disease development. We investigated putative associations with deprivation and population density. Methods Data on osteosarcoma and Ewing sarcoma were obtained from national population-based registries. Negative binomial regression was used to examine the relationship between incidence rates and the Townsend deprivation score (and its component variables) and small-area population density. Results The study analyzed 2566 osteosarcoma and 1650 Ewing sarcoma cases. For females with osteosarcoma, statistically significant decreased risk was associated with higher levels of deprivation (relative risk [RR] per unit increase in deprivation score = 0.969; 95% confidence interval [CI] 0.946–0.993). For all Ewing sarcoma combined, statistically significant decreased risk was associated with greater area-level population density and higher levels of non-car ownership (RR per person per hectare increase = 0.984; 95% CI 0.976–0.993, RR per 1% increase in non-car ownership = 0.994; 95% CI 0.991–0.998). Conclusions Higher incidence of osteosarcoma was observed for females in areas with lower deprivation levels indicating increased risk is linked to some aspect of affluent living. Higher incidence of Ewing sarcoma occurred in areas of low population density and where more people owned cars, both characteristic of rural environments. The study adds substantially to evidence associating Ewing sarcoma risk with rural environmental exposures. Putative risk factors include agricultural exposures, such as pesticides and zoonotic agents.

Background Epidemiological studies from Europe and North America have provided evidence that exposure to air pollution can aggravate symptoms in asthmatic patients. Methods Daily number of AEDv, air pollution levels (PM10, PM2.5, SO2, NO2 and CO) and meteorological variables was obtained from Jubail Industrial City, Saudi Arabia, for the period of 2007–11. Data were analyzed using a time-series approach. Relative risks (RRs) were estimated using Poisson regression. Results The associations between AEDv and PM10, PM2.5, SO2 and NO2 remained positive and statistically significant after mutual adjustment in the multi-pollutant model. The RR of AEDv increased by 5.4, 4.4, 3.4 and 2.2% per an inter-quartile range increase in SO2 (2.0 ppb), PM2.5 (36 μg/m3), NO2 (7.6 ppb) and PM10 (140 μg/m3), respectively. No significant associations between AEDv and CO were found. Conclusions Current levels of ambient air pollution are associated with AEDv in this industrial setting in the Middle East. Greater awareness of environmental health protection and the implementation of effective measures to improve the quality of air in such settings would be beneficial to public health. [ABSTRACT FROM AUTHOR]

Abstract: Mitochondrial disease associated with the pathogenic m.3243A>G variant is a common, clinically heterogeneous, neurogenetic disorder. Using multiple linear regression and linear mixed modelling, we evaluated which commonly assayed tissue (blood N = 231, urine N = 235, skeletal muscle N = 77) represents the m.3243A>G mutation load and mitochondrial DNA (mtDNA) copy number most strongly associated with disease burden and progression. m.3243A>G levels are correlated in blood, muscle and urine (R2 = 0.61–0.73). Blood heteroplasmy declines by ~2.3%/year; we have extended previously published methodology to adjust for age. In urine, males have higher mtDNA copy number and ~20% higher m.3243A>G mutation load; we present formulas to adjust for this. Blood is the most highly correlated mutation measure for disease burden and progression in m.3243A>G‐harbouring individuals; increasing age and heteroplasmy contribute (R2 = 0.27, P < 0.001). In muscle, heteroplasmy, age and mtDNA copy number explain a higher proportion of variability in disease burden (R2 = 0.40, P < 0.001), although activity level and disease severity are likely to affect copy number. Whilst our data indicate that age‐corrected blood m.3243A>G heteroplasmy is the most convenient and reliable measure for routine clinical assessment, additional factors such as mtDNA copy number may also influence disease severity. [ABSTRACT FROM AUTHOR]

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: 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.)

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).)

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.

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.)

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.

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.