The effect of comorbidities on diagnostic interval for lung cancer in England: a cohort study using electronic health record data.

BACKGROUND: Comorbid conditions may delay lung cancer diagnosis by placing demand on general practioners' time reducing the possibility of prompt cancer investigation ("competing demand conditions"), or by offering a plausible non-cancer explanation for signs/symptoms ("alternative explanation conditions"). METHOD: Patients in England born before 1955 and diagnosed with incident lung cancer between 1990 and 2019 were identified in the Clinical Practice Research Datalink and linked hospital admission and cancer registry data. Diagnostic interval was defined as time from first presentation in primary care with a relevant sign/symptom to the diagnosis date. 14 comorbidities were classified as ten "competing demand" and four "alternative explanation" conditions. Associations with diagnostic interval were investigated using multivariable linear regression models. RESULTS: Complete data were available for 11870 lung cancer patients. In adjusted analyses diagnostic interval was longer for patients with "alternative explanation" conditions, by 31 and 74 days in patients with one and ≥2 conditions respectively versus those with none. Number of "competing demand" conditions did not remain in the final adjusted regression model for diagnostic interval. CONCLUSIONS: Conditions offering alternative explanations for lung cancer symptoms are associated with increased diagnostic intervals. Clinical guidelines should incorporate the impact of alternative and competing causes upon delayed diagnosis.

The Sussex COVID-19 Modelling Cell: the methods and successes of a collaboration between public health teams in local authorities, NHS hospital trusts, NHS commissioners, and universities.

BACKGROUND: The Sussex Modelling Cell (SMC) is a consortium, formed during the COVID-19 pandemic, of representatives from NHS Sussex, and the local authorities and universities in Sussex. The SMC aimed to provide public health teams with local-data-driven modelling, data analysis, and policy and commissioning advice to mitigate the impact of the pandemic on the local population. It also aimed to answer operational questions, since the Government's forecasts were not suitably applicable. METHODS: From March 23, 2020, the SMC met (virtually) every Thursday to monitor COVID-19 situation reports, answer queries related to data and modelling, and provide interpretations of data or reports from many internal and external sources. SMC also provided quantitative information for public health teams to use within their organisations to advise on the local epidemic picture. Among other tools, the SMC calibrated a mathematical model to local COVID-19 data that could forecast health-care and hospital demand and COVID-19-related deaths. FINDINGS: Throughout the pandemic, the SMC provided scientific and data-driven evidence on the necessity of body storage contracts, monetary support for urgent care, and operational adjustments surrounding health-care provisions. The scientific evidence was generated and used repeatedly in each organisation to make beneficial decisions in a time of crisis. Although chasing an ever-changing pandemic picture was challenging, our swift reaction to national policy and pandemic changes allowed us to support policymakers, reduce anxiety, and provide clarity on the next steps. Our collaboration is one among few across the country and thus should be not only celebrated but also replicated, with appropriate resources and funding. INTERPRETATION: Besides mitigating the direct impact of the COVID-19 situation in Sussex, we have established a scientific collaboration relationship, in contrast to a customer-consultant setting, allowing the group to incorporate both the technical and applied perspectives into the work. With a clear structure, ethos and methodology, the SMC is able to step into the gap between academia and public health modelling to consider different impactful questions of operational importance where underlying complicated models exist, such as waiting times or system demand and capacity, and provide data analytic upskilling to public health teams. FUNDING: Brighton and Hove City Council, East and West Sussex County Council, and Sussex Health and Care Partnership.

Disparities in oesophageal cancer risk by age, sex, and nativity in Kuwait:1980-2019.

BACKGROUND: This cross-sectional cohort study assessed the inequalities in oesophageal carcinoma risk by age, sex and nativity in Kuwait: 1980-2019. METHODS: Using oesophageal cancer incidence data from the Kuwait National Cancer Registry, relevant Kuwaiti population data and World Standard Population as a reference, age-standardized incidence rates (ASIR) (per 100,000 person-years) overall and by subcohorts were computed. The incident oesophageal cancer cases count was overdispersed with excessive structural zeros, therefore, it was analyzed using multivariable zero-inflated negative binomial (ZINB) model. RESULTS: Overall ASIR of oesophageal cancer was 10.51 (95% CI:  6.62-14.41). The multivariable ZINB model showed that compared with the younger age category (< 30 years), the individuals in higher age groups showed a significant (p < 0.001) increasing tendency to develop the oesophageal cancer.  Furthermore, compared with the non-Kuwaiti residents, the Kuwaiti nationals were significantly (p < 0.001) more likely to develop oesophageal cancer during the study period. Moreover, compared with 1980-84 period, ASIRs steadily and significantly  (p < 0.005) declined in subsequent periods till 2015-19. CONCLUSIONS: A high incidence of oesophageal cancer was recorded in Kuwait, which consistently declined from 1980 to 2019. Older adults (aged ≥ 60 years) and, Kuwaiti nationals were at high risk of oesophageal cancer. Focused educational intervention may minimize oesophageal cancer incidence in high-risk groups in this and other similar settings. Future studies may contemplate to evaluate such an intervention.

Association between naturally occurring lithium in drinking water and suicide rates: systematic review and meta-analysis of ecological studies.

BACKGROUND: The prevalence of mental health conditions and national suicide rates are increasing in many countries. Lithium is widely and effectively used in pharmacological doses for the treatment and prevention of manic/depressive episodes, stabilising mood and reducing the risk of suicide. Since the 1990s, several ecological studies have tested the hypothesis that trace doses of naturally occurring lithium in drinking water may have a protective effect against suicide in the general population. AIMS: To synthesise the global evidence on the association between lithium levels in drinking water and suicide mortality rates. METHOD: The MEDLINE, Embase, Web of Science and PsycINFO databases were searched to identify eligible ecological studies published between 1 January 1946 and 10 September 2018. Standardised regression coefficients for total (i.e. both genders combined), male and female suicide mortality rates were extracted and pooled using random-effects meta-analysis. The study was registered with PROSPERO (CRD42016041375). RESULTS: The literature search identified 415 articles; of these, 15 ecological studies were included in the synthesis. The random-effects meta-analysis showed a consistent protective (or inverse) association between lithium levels/concentration in publicly available drinking water and total (pooled ß = -0.27, 95% CI -0.47 to -0.08; P = 0.006, I2 = 83.3%), male (pooled ß = -0.26, 95% CI -0.56 to 0.03; P = 0.08, I2 = 91.9%) and female (pooled ß = -0.13, 95% CI -0.24 to -0.02; P = 0.03, I2 = 28.5%) suicide mortality rates. A similar protective association was observed in the six studies included in the narrative synthesis, and subgroup meta-analyses based on the higher/lower suicide mortality rates and lithium levels/concentration. CONCLUSIONS: This synthesis of ecological studies, which are subject to the ecological fallacy/bias, supports the hypothesis that there is a protective (or inverse) association between lithium intakes from public drinking water and suicide mortality at the population level. Naturally occurring lithium in drinking water may have the potential to reduce the risk of suicide and may possibly help in mood stabilisation, particularly in populations with relatively high suicide rates and geographical areas with a greater range of lithium concentration in the drinking water. All the available evidence suggests that randomised community trials of lithium supplementation of the water supply might be a means of testing the hypothesis, particularly in communities (or settings) with demonstrated high prevalence of mental health conditions, violent criminal behaviour, chronic substance misuse and risk of suicide.

Resilience-based alcohol education: developing an intervention, evaluating feasibility and barriers to implementation using mixed-methods.

Alcohol education must ensure that young people have appropriate information, motivation and skills. This article describes the fifth phase in a program of intervention development based on principles of social marketing and intervention mapping. The aim was to enhance drink refusal self-efficacy (DRSE) and help develop skills for non-drinking or moderate drinking. We conducted a mixed-methods feasibility trial that measured intervention effects among 277 UK secondary school students aged 14-16, and used qualitative methods to explore four teachers' experiences of delivering the intervention. The intervention did not produce the desired changes in DRSE or alcohol use, but nor did it increase alcohol use. In the qualitative process evaluation, time constraints, pressure to prioritize other topics, awkwardness and embarrassment were identified as barriers to fidelitous delivery. A more intense and/or more prolonged intervention delivered with greater fidelity may have produced the desired changes in DRSE and alcohol use. This study illustrates how principles of social marketing and intervention mapping can aid development of resilience-based education designed to help students develop skills to drink moderately, or not drink. It also highlights the need to consider the constraints of micro-social (school) and macro-social (societal) cultures when designing alcohol education.

A systematic review of economic evaluations of local authority commissioned preventative public health interventions in overweight and obesity, physical inactivity, alcohol and illicit drugs use and smoking cessation in the United Kingdom.

Background: Since 2013, local authorities in England have been responsible for commissioning preventative public health interventions. The aim of this systematic review was to support commissioning by collating published data on economic evaluations and modelling of local authority commissioned public health preventative interventions in the UK. Methods: Following the PRISMA protocol, we searched for economic evaluations of preventative intervention studies in four different areas: overweight and obesity, physical inactivity, alcohol and illicit drugs use and smoking cessation. The systematic review identified studies between January 1994 and February 2015, using five databases. We synthesized the studies to identify the key methods and examined results of the economic evaluations. Results: The majority of the evaluations related to cost-effectiveness, rather than cost-benefit analyses or cost-utility analyses. These analyses found preventative interventions to be cost effective, though the context of the interventions differed between the studies. Conclusions: Preventative public health interventions in general are cost-effective. There is a need for further studies to support justification of continued and/or increased funding for public health interventions. There is much variation between the types of economically evaluated preventative interventions in our review. Broader studies incorporating different contexts may help support funding for local authority-sponsored public health initiatives.

Molecular basis for the effects of zinc deficiency on spermatogenesis: An experimental study in the Sprague-dawley rat model.

INTRODUCTION: The objective of this study is to investigate the molecular mechanisms underlying the effects of zinc deficiency on spermatogenesis in the Sprague-Dawley (SD) rat. MATERIALS AND METHODS: Three groups of eight adult male SD rats were maintained for 4 weeks on a normal diet as control, zinc deficient diet and zinc deficient diet with zinc supplementation of 28 mg zinc/kg body weight respectively. Using standard techniques, the following parameters were compared between the three groups of experimental animals at the end of 4 weeks: (a) Serum zinc, magnesium (Mg), copper (Cu), selenium (Se) and cadmium (Cd), (b) serum sex hormones, malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GPX), (c) interleukin-4 (IL-4), tumor necrosis factor-alpha (TNF-α), Bcl-2, Bax and caspase-3 expression in the testes, (d) assessment of apoptosis of testicular cells using electron microscopy and (e) testicular volume and histology using the orchidometer and Johnsen score, respectively. RESULTS: The zinc deficient group showed a reduction of testicular volume, serum concentrations of Zn, Cu, Se, Mg, SOD, GPX, IL-4, Bcl-2 and testosterone (P < 0.05), as well as increased levels of serum Cd, MDA and tissue TNF-α, Bax, caspase-3 and apoptosis of the germ cells (P < 0.05) compared with control and zinc supplementation groups. CONCLUSION: Zinc deficiency is associated with impaired spermatogenesis because of reduced testosterone production, increased oxidative stress and apoptosis. These findings suggest that zinc has a role in male reproduction.

Demography and clinical course of ulcerative colitis in Arabs - a study based on the Montreal classification.

OBJECTIVE: Ulcerative colitis (UC) is generally considered a disease of the Caucasian populations in developed countries, but its incidence is increasing rapidly in many developing countries, including the Middle East. The objective of this study was to determine the clinical epidemiology of UC in Arabs. MATERIAL AND METHODS: This cross-sectional medical record-based descriptive study collected sociodemographic and clinical information on 182 Arab patients with UC in Kuwait. Age at diagnosis, extent and severity of disease were determined according to the Montreal classification. results: Among the 182 patients, 91 (50.0%) were males. The median age at diagnosis was 28.5 years. Family history of UC was reported by 26 (14.3%) patients. The extent of the disease was limited to the rectum in 34 (18.7%) patients, left sided in 67 (36.8%) and pan colitis in 81 (44.5%). At the time of inclusion in the study, 127 (69.8%) patients were in clinical remission, 53 (29.1%) had mild-to-moderate disease and 2 (1.1%) had severe colitis. Younger age at diagnosis and non-smoking were associated with more extensive colitis. The majority of patients were treated with mesalamine, steroids and immunomodulators, while biologic therapy and surgery were needed in 5% and 4% of the patients, respectively. CONCLUSIONS: UC presents more commonly at younger age among Arabs in Kuwait. Extensive disease at presentation is associated with younger age at diagnosis and absence of tobacco smoking. There also appears to be less need for surgery and biologic therapy for the disease in this population.

Visible damp in a child's bedroom is associated with increased respiratory morbidity in early life: a multicentre cohort study.

OBJECTIVE: Household damp exposure is an important public health issue. We aimed to assess the impact of the location of household damp on respiratory outcomes during early life. METHODS: Household damp exposure was ascertained in children recruited to the GO-CHILD multicentre birth cohort study. The frequency of respiratory symptoms, infections, healthcare utilisation and medication prescription for wheezing were collected by postal questionnaires at 12 and 24 months. Log binomial and ordered logistic regression models were fitted to the data. RESULTS: Follow-up was obtained in 1344 children between August 2010 and January 2016. Visible damp was present in a quarter of households (25.3%) with 1 in 12 children's bedrooms affected (8.3%). Damp in the bathroom, kitchen or living room was not associated with any respiratory or infection-related outcomes. Damp in the child's bedroom was associated with an increased risk of dry cough (8.7% vs 5.7%) (adjusted relative risk 1.56, 95% CI 1.07 to 2.27; p=0.021) and odds of primary care attendance for cough and wheeze (7.6% vs 4.4%) (adjusted OR 1.37, 95% CI 1.07 to 1.76; p=0.009). There were also increased risk of inhaled corticosteroid (13.3% vs 5.9%) (adjusted RR 2.22, 95% CI 1.04 to 4.74; p=0.038) and reliever inhaler (8.3% vs 5.8%) (adjusted RR 2.01, 95% CI 1.21 to 2.79; p=0.018) prescription. CONCLUSION: Damp in the child's bedroom was associated with increased respiratory morbidity. In children presenting with recurrent respiratory symptoms, clinicians should enquire about both the existence and location of damp, the presence of which can help prioritise those families requiring urgent household damp assessment and remediation works.

Environmental risk factors for respiratory infection and wheeze in young children: A multicentre birth cohort study.

INTRODUCTION: Respiratory infections and wheeze have a considerable impact on the health of young children and consume significant healthcare resources. We aimed to evaluate the effect of environmental factors on respiratory infections and symptoms in early childhood. METHODS: Environmental risk factors including: daycare attendance; breastfeeding; siblings; damp within the home; environmental tobacco smoke (ETS); child's bedroom flooring; animal exposure; road traffic density around child's home; and solid fuel pollution within home were assessed in children recruited to the GO-CHILD multicentre prospective birth cohort study. Follow-up information on respiratory infections (bronchiolitis, pneumonia, otitis media and cold or flu), wheeze and cough symptoms, healthcare utilisation and medication prescription was collected by postal questionnaires at 12 and 24 months. Log binomial and ordered logistic regression models were fitted to the data. RESULTS: Follow-up was obtained on 1344 children. Daycare was associated with increased odds of pneumonia (odds ratio [OR] = 2.39, 95% confidence interval [CI]: 1.04-5.49), bronchiolitis (OR = 1.40, 1.02-1.90), otitis media (OR = 1.68, 1.32-2.14) and emergency department attendance for wheeze (RR = 1.81, 1.17-2.80). Breastfeeding beyond 6 months was associated with a reduced odds of bronchiolitis (OR = 0.55, 0.39-0.77) and otitis media (OR = 0.75, 0.59-0.99). Siblings at home was associated with an increased odds of bronchiolitis (OR = 1.65, 1.18-2.32) and risk of reliever inhaler prescription (RR = 1.37, 1.02-1.85). Visible damp was associated with an increased odds of wheeze (OR = 1.85, 1.11-3.19), and risk of reliever inhaler (RR = 1.73, 1.04-2.89) and inhaled corticosteroid prescription (RR = 2.61, 1.03-6.59). ETS exposure was associated with an increased odds of primary care attendance for cough or wheeze (OR = 1.52, 1.11-2.08). Dense traffic around the child's home was associated with an increased odds of bronchiolitis (OR = 1.32, 1.08-2.29). CONCLUSION: Environmental factors likely influence the wide variation in infection frequency and symptoms observed in early childhood. Larger population studies are necessary to further inform and guide public health policy to decrease the burden of respiratory infections and wheeze in young children.

Factors associated with smoking relapse in the postpartum period: an analysis of the child health surveillance system data in Southeast England.

INTRODUCTION: There is increasing evidence that a high proportion (47%-63%) of women who quit smoking during pregnancy relapse during the postpartum period. The purpose of this population-based study was to examine the association between selected sociodemographic factors and smoking relapse in the early postpartum period (within the first 6 weeks) in women who had successfully quit smoking during the pregnancy. METHODS: The study included 512 women resident in East Sussex, United Kingdom, who had quit smoking during the pregnancy. Information on the prevalence of smoking and selected sociodemographic factors and breast feeding at the 6-weeks postpartum review by health visitor was obtained from the Child Health Surveillance System, which records and monitors the health and development of children from birth until school entry. RESULTS: Of the 512 women who had quit smoking during the pregnancy, 238 (46.5%) relapsed in the early postpartum period. In the bivariate analysis, there was an association between deprivation and smoking relapse in the early postpartum period (OR = 5.3, 95% CI: 2.5-11.4), with a significant trend in increasing risk of relapse with increasing level of deprivation (p < .01). Stepwise logistic regression analysis showed that women who lived in deprived urban areas (OR = 2.3, 95% CI: 1.2-4.2), had ≥3 children (OR = 3.8, 95% CI: 2.2-6.4), and had other smokers in the household (OR = 5.6, 95% CI: 3.6-8.8) were significantly more likely to relapse in the early postpartum period. On the other hand, women who were breast feeding were significantly less likely to relapse (OR = 0.6, 95% CI: 0.4-0.9). CONCLUSIONS: Factors associated with early postpartum smoking relapse identified in this study, particularly breast feeding, high parity, and concurrent smoking by partner/other household member(s), may contribute to the development of effective and targeted interventions to maintain smoking cessation in women and their household.

A hospital demand and capacity intervention approach for COVID-19.

The mathematical interpretation of interventions for the mitigation of epidemics in the literature often involves finding the optimal time to initiate an intervention and/or the use of the number of infections to manage impact. Whilst these methods may work in theory, in order to implement effectively they may require information which is not likely to be available in the midst of an epidemic, or they may require impeccable data about infection levels in the community. In reality, testing and cases data can only be as good as the policy of implementation and the compliance of the individuals, which implies that accurately estimating the levels of infections becomes difficult or complicated from the data that is provided. In this paper, we demonstrate a different approach to the mathematical modelling of interventions, not based on optimality or cases, but based on demand and capacity of hospitals who have to deal with the epidemic on a day to day basis. In particular, we use data-driven modelling to calibrate a susceptible-exposed-infectious-recovered-died type model to infer parameters that depict the dynamics of the epidemic in several regions of the UK. We use the calibrated parameters for forecasting scenarios and understand, given a maximum capacity of hospital healthcare services, how the timing of interventions, severity of interventions, and conditions for the releasing of interventions affect the overall epidemic-picture. We provide an optimisation method to capture when, in terms of healthcare demand, an intervention should be put into place given a maximum capacity on the service. By using an equivalent agent-based approach, we demonstrate uncertainty quantification on the likelihood that capacity is not breached, by how much if it does, and the limit on demand that almost guarantees capacity is not breached.

Health and wellbeing of Nepalese migrant workers in Gulf Cooperation Council (GCC) countries: A mixed-methods study.

Introduction: Migrant workers support low- and middle-income economies through remittances, often bearing considerable health risks with long-term consequences. This study aims to understand the health and wellbeing issues of Nepalese migrant workers in Gulf Cooperation Council (GCC) countries, a major destination for low-skilled Nepalese workers. Methodology: We conducted a mixed-methods study in Dhading district of Nepal. A pilot survey was carried out with returnee migrants from GCC countries to understand key health and wellbeing issues faced by workers. In addition, in-depth interviews were conducted with a subset of these returnee migrants and their families, and related stakeholders. These aimed to understand broader societal and policy implications in relation to labour migration. Quantitative data from the survey were analysed using descriptive statistics and thematic analysis was used for qualitative interviews. Results: 60 returnee migrants (58 males, 2 females) took part in the survey (response rate, 100%). Median age of the survey participants was 34 (IQR, 9) years and 68% had completed school level education. Returnee migrants reported suffering from various physical and mental health issues during their stay in GCC countries including cold/fever (42%), mental health problems (25%) and verbal abuse (35%). 20 participants took part in the qualitative study:10 returnee migrants (8 males, 2 females), four family members (female spouses) and six key stakeholders working in organizations related to international migration. Interview participants reported severe weather conditions resulting in physical health problems (e.g. pneumonia, dehydration and kidney disease) as well as mental health issues (including anxiety, loneliness and depression). Participants raised concerns about the usefulness and appropriateness of pre-departure training, and the authenticity of medical tests and reports in Nepal. Female migrants reported facing stigma after returning home from abroad. Language difficulties, alongside issues related to payment, insurance and support at work were cited as barriers to accessing healthcare in destination countries. Conclusion: Our study shows that Nepalese migrant workers experience severe weather conditions and suffer from various physical and mental health issues, including workplace abuse and exploitation. The study highlights an urgent need for strategies to enforce compulsory relevant pre-departure orientation and appropriate medical screening in Nepal, and fair employment terms and full health insurance coverage in destination countries. Greater collaboration between the Nepalese government and GCC countries is needed to ensure necessary legislation and regulatory frameworks are in place to safeguard the health and wellbeing of migrant workers.

The Contribution of Environmental Science to Mental Health Research: A Scoping Review.

Mental health is influenced by multiple complex and interacting genetic, psychological, social, and environmental factors. As such, developing state-of-the-art mental health knowledge requires collaboration across academic disciplines, including environmental science. To assess the current contribution of environmental science to this field, a scoping review of the literature on environmental influences on mental health (including conditions of cognitive development and decline) was conducted. The review protocol was developed in consultation with experts working across mental health and environmental science. The scoping review included 202 English-language papers, published between 2010 and 2020 (prior to the COVID-19 pandemic), on environmental themes that had not already been the subject of recent systematic reviews; 26 reviews on climate change, flooding, air pollution, and urban green space were additionally considered. Studies largely focused on populations in the USA, China, or Europe and involved limited environmental science input. Environmental science research methods are primarily focused on quantitative approaches utilising secondary datasets or field data. Mental health measurement was dominated by the use of self-report psychometric scales. Measures of environmental states or exposures were often lacking in specificity (e.g., limited to the presence or absence of an environmental state). Based on the scoping review findings and our synthesis of the recent reviews, a research agenda for environmental science's future contribution to mental health scholarship is set out. This includes recommendations to expand the geographical scope and broaden the representation of different environmental science areas, improve measurement of environmental exposure, prioritise experimental and longitudinal research designs, and giving greater consideration to variation between and within communities and the mediating pathways by which environment influences mental health. There is also considerable opportunity to increase interdisciplinarity within the field via the integration of conceptual models, the inclusion of mixed methods and qualitative approaches, as well as further consideration of the socio-political context and the environmental states that can help support good mental health. The findings were used to propose a conceptual model to parse contributions and connections between environmental science and mental health to inform future studies.

Association between Smokeless Tobacco Use and Waterpipe Smoking and the Risk of Lung Cancer: A Systematic Review and Meta-Analysis of Current Epidemiological Evidence.

BACKGROUND: Smokeless tobacco and waterpipes are used by hundreds of millions of people worldwide and consumption rates exceed that of cigarette smoking in much of South East Asia and parts of the Middle East. However, the cancer risks of these methods of tobacco consumption are less well-characterized than those of cigarette smoking. The objective of this study was to systematically review the epidemiological evidence on the association between smokeless tobacco use and waterpipe smoking and lung cancer risk. METHODS: The MEDLINE, EMBASE, Web of Science and OpenSIGLE databases were searched to identify eligible case-control and cohort studies (published before 1st December 2020 in any language) that adjusted for cigarette smoking or included non-cigarette smokers only. Summary odds ratio/relative risk estimates and confidence intervals were extracted, and pooled risk ratios (RRs) for lung cancer were calculated using random effects meta-analysis. RESULTS: The literature search identified 2,465 publications: of these, 26 studies including 6,903 lung cancer patients were included in the synthesis (20 studies of smokeless tobacco use, five of waterpipe smoking, one of both). Our results suggest that smokeless tobacco use is associated with an increased risk of lung cancer among non-cigarette smokers, and that betel quid tobacco may be particularly hazardous. The random effects meta-analysis showed that exclusive use of any type of smokeless tobacco (pooled RR = 1.53, 95%CI 1.09 - 2.14), betel quid chewing (pooled RR = 1.77, 95%CI 1.06 - 2.95), and waterpipe smoking (pooled RR = 3.25, 95%CI 2.01 - 5.25) were significantly associated with an increased risk of lung cancer. CONCLUSIONS: This meta-analysis of case-control/cohort studies supports the hypothesis that use of smokeless tobacco and waterpipe smoking is associated with increased risk of developing lung cancer. Considering the widespread and increasing use of smokeless tobacco in developing countries, and increasing prevalence of waterpipe smoking in almost all societies, these findings inform formulation of public health policy, legislation and tobacco control measures at national and international level to increase awareness and decrease the prevalence of smokeless tobacco use and waterpipe smoking.

Mannose-binding lectin genotype is associated with respiratory disease in young children: A multicenter cohort study.

BACKGROUND: Mannose-binding lectin (MBL) is an important component of the innate immune system. Polymorphisms in the MBL2 gene and promoter region are directly associated with MBL-deficiency. We sought to determine the association between MBL genotype on the frequency of common childhood respiratory infections, respiratory symptoms, and atopic outcomes in early childhood. METHODS: MBL2 gene variants were analyzed in newborns recruited to the GO-CHILD multicenter prospective cohort study. Follow-up for respiratory infection and atopy diagnoses and symptoms, healthcare utilization, and medication prescription were conducted by postal questionnaires at 12 and 24 months. RESULTS: Genotyping and follow-up were completed in 1004 children. Genotypes associated with MBL-deficiency were associated with an increased risk of bronchiolitis (relative risk [RR] 1.95, 95% confidence interval [CI] 1.33-2.85) and pneumonia (RR 2.46, 95% CI 1.16-5.22). MBL-deficient genotypes were associated with an increased risk of wheeze with shortness of breath episodes (RR 1.22, 95% CI 1.04-1.43), emergency department attendance (RR 1.90 95% CI 1.13-3.19), and hospital admission (RR 2.01, 95% CI 1.04-3.89) for wheeze. MBL-deficient genotypes were associated with a reduced risk of developing atopic dermatitis (RR 0.72, 95% CI 0.53-0.98). CONCLUSION: The positive association between MBL-deficient genotypes and bronchiolitis and pneumonia, as well as a severe wheeze phenotype in some young children, supports the hypothesis that MBL is an important component of innate immunity in the vulnerable period before the maturation of the adaptive immune system. Identification of disease-modifying genotypes may help target preventative strategies in high-risk infants.

Lithium in drinking water and suicide rates across the East of England.

Lithium can be found naturally in drinking water. In clinical practice, it is widely used in pharmacological doses for the treatment of bipolar disorder; and may also prevent suicidal behaviour in people with mood disorders. In two studies, lithium levels in tap water have been significantly and negatively correlated with suicide. We measured lithium levels in tap water in the 47 subdivisions of the East of England and correlated these with the respective suicide standardised mortality ratio in each subdivision. We found no association between lithium in drinking water and suicide rates across the East of England from 2006 to 2008.

Changing epidemiology and age-specific incidence of cutaneous malignant melanoma in England: An analysis of the national cancer registration data by age, gender and anatomical site, 1981-2018.

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).