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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]

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.)