Lesley Rushton

Assessing the human health impacts of exposure to disinfection by-products — A critical review of concepts and methods ☆

Understanding the public health implications of chemical contamination of drinking water is important for societies and their decision-makers. The possible population health impacts associated with exposure to disinfection by-products (DBPs) are of particular interest due to their potential carcinogenicity and their widespread occurrence as a result of treatments employed to control waterborne infectious disease. We searched the literature for studies that have attempted quantitatively to assess population health impacts and health risks associated with exposure to DBPs in drinking water. We summarised and evaluated these assessments in terms of their objectives, methods, treatment of uncertainties, and interpretation and communication of results. In total we identified 40 studies matching our search criteria. The vast majority of studies presented estimates of generic cancer and non-cancer risks based on toxicological data and methods that were designed with regulatory, health-protective purposes in mind, and therefore presented imprecise and biased estimates of health impacts. Many studies insufficiently addressed the numerous challenges to DBP risk assessment, failing to evaluate the evidence for a causal relationship, not appropriately addressing the complex nature of DBP occurrence as a mixture of chemicals, not adequately characterising exposure in space and time, not defining specific health outcomes, not accounting for characteristics of target populations, and not balancing potential risks of DBPs against the health benefits related with drinking water disinfection. Uncertainties were often poorly explained or insufficiently accounted for, and important limitations of data and methods frequently not discussed. Grave conceptual and methodological limitations in study design, as well as erroneous use of available dose-response data, seriously impede the extent to which many of these assessments contribute to understanding the public health implications of exposure to DBPs. In some cases, assessment results may cause unwarranted alarm among the public and potentially lead to poor decisions being made in sourcing, treatment, and provision of drinking water. We recommend that the assessment of public health impacts of DBPs should be viewed as a means of answering real world policy questions relating to drinking water quality, including microbial contaminants; that they should be conducted using the most appropriate and up-to-date data and methods, and that associated uncertainties and limitations should be accounted for using quantitative methods where appropriate.

The proportion of cancer attributable to occupational exposures

PURPOSEnTo review the literature on the estimation of the population attributable fraction (PAF) of cancer due to occupational exposures and to describe challenges in the estimation of this metric. To help illustrate the inherent challenges, we also estimate PAFs for selected cancers diagnosed in the United States in 2010 attributable to work as a painter (causally associated with bladder and lung cancer) and shift work (possibly associated with breast cancer).nnnMETHODSnWe reviewed and summarized previous reports providing quantitative estimates of PAF for total cancer due to occupational exposures. We calculated PAF estimates for painters and shift work using methodology from a detailed investigation of the occupational cancer burden in Great Britain, with adaptations made for the US population.nnnRESULTSnThe estimated occupation-attributable fraction for total cancer generally ranged between 2% and 8% (men, 3%-14%; women, 1%-2%) based on previous reports. We calculated that employment as a painter accounted for a very small proportion of cancers of the bladder and lung diagnosed in the United States in 2010, with PAFs of 0.5% for each site. In contrast, our calculations suggest that the potential impact of shift work on breast cancer (if causal) could be substantial, with a PAF of 5.7%, translating to 11,777 attributable breast cancers.nnnCONCLUSIONSnContinued efforts to estimate the occupational cancer burden will be important as scientific evidence and economic trends evolve. Such projects should consider the challenges involved in PAF estimation, which we summarize in this report.

House dust mite reduction and avoidance measures for treating eczema

BACKGROUNDnEczema is an inflammatory skin disease that tends to involve skin creases, such as the folds of the elbows or knees; it is an intensely itchy skin condition, which can relapse and remit over time. As many as a third of people with eczema who have a positive test for allergy to house dust mite have reported worsening of eczema or respiratory symptoms when exposed to dust.nnnOBJECTIVESnTo assess the effects of all house dust mite reduction and avoidance measures for the treatment of eczema.nnnSEARCH METHODSnWe searched the following databases up to 14 August 2014: the Cochrane Skin Group Specialised Register, CENTRAL in The Cochrane Library (2014, Issue 8), MEDLINE (from 1946), Embase (from 1974), LILACS (from 1982), and the GREAT database. We also searched five trials registers and checked the reference lists of included and excluded studies for further references to relevant studies. We handsearched abstracts from international eczema and allergy meetings.nnnSELECTION CRITERIAnRandomised controlled trials (RCTs) of any of the house dust mite reduction and avoidance measures for the treatment of eczema, which included participants of any age diagnosed by a clinician with eczema as defined by the World Allergy Organization. We included all non-pharmacological and pharmacological interventions that sought to reduce or avoid exposure to house dust mite and their allergenic faeces. The comparators were any active treatment, no treatment, placebo, or standard care only.nnnDATA COLLECTION AND ANALYSISnTwo authors independently checked the titles and abstracts identified, and there were no disagreements. We contacted authors of included studies for additional information. We assessed the risk of bias using Cochrane methodology.nnnMAIN RESULTSnWe included seven studies of 324 adults and children with eczema. Overall, the included studies had a high risk of bias. Four of the seven trials tested interventions with multiple components, and three tested a single intervention. Two of the seven trials included only children, four included children and adults, and one included only adults. Interventions to reduce or avoid exposure to house dust mite included covers for mattresses and bedding, increased or high-quality vacuuming of carpets and mattresses, and sprays that kill house dust mites.Four studies assessed our first primary outcome of Clinician-assessed eczema severity using a named scale. Of these, one study (n = 20) did not show any significant short-term benefit from allergen impermeable polyurethane mattress encasings and acaricide spray versus allergen permeable cotton mattress encasings and placebo acaricide spray. One study (n = 60) found a modest statistically significant benefit in the Six Area, Six Sign Atopic Dermatitis (SASSAD) scale over six months (mean difference of 4.2 (95% confidence interval 1.7 to 6.7), P = 0.008) in favour of a mite impermeable bedding system combined with benzyltannate spray and high-filtration vacuuming versus mite permeable cotton encasings, water with a trace of alcohol spray, and a low-filtration vacuum cleaner. The third study (n = 41) did not compare the change in severity of eczema between the two treatment groups. The fourth study (n = 86) reported no evidence of a difference between the treatment groups.With regard to the secondary outcomes Participant- or caregiver-assessed global eczema severity score and the Amount and frequency of topical treatment required, one study (n = 20) assessed these outcomes with similar results being reported for these outcomes in both groups. Four studies (n = 159) assessed Sensitivity to house dust mite allergen using a marker; there was no clear evidence of a difference in sensitivity levels reported between treatments in any of the four trials.None of the seven included studies assessed our second primary outcome Participant- or caregiver-assessed eczema-related quality of life using a named instrument or the secondary outcome of Adverse effects.We were unable to combine any of our results because of variability in the interventions and paucity of data.nnnAUTHORS CONCLUSIONSnWe were unable to determine clear implications to inform clinical practice from the very low-quality evidence currently available. The modest treatment responses reported were in people with atopic eczema, specifically with sensitivity to one or more aeroallergens. Thus, their use in the eczema population as a whole is unknown. High-quality long-term trials of single, easy-to-administer house dust mite reduction or avoidance measures are worth pursuing.

Stomach cancer and occupational exposure to asbestos: a meta-analysis of occupational cohort studies.

Background:A recent Monographs Working Group of the International Agency for Research on Cancer concluded that there is limited evidence for a causal association between exposure to asbestos and stomach cancer.Methods:We performed a meta-analysis to quantitatively evaluate this association. Random effects models were used to summarise the relative risks across studies. Sources of heterogeneity were explored through subgroup analyses and meta-regression.Results:We identified 40 mortality cohort studies from 37 separate papers, and cancer incidence data were extracted for 15 separate cohorts from 14 papers. The overall meta-SMR for stomach cancer for total cohort was 1.15 (95% confidence interval 1.03–1.27), with heterogeneous results across studies. Statistically significant excesses were observed in North America and Australia but not in Europe, and for generic asbestos workers and insulators. Meta-SMRs were larger for cohorts reporting a SMR for lung cancer above 2 and cohort sizes below 1000.Conclusions:Our results support the conclusion by IARC that exposure to asbestos is associated with a moderate increased risk of stomach cancer.

Occupations associated with COPD risk in the large population-based UK Biobank cohort study

Objectives Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide. Exposure to occupational hazards is an important preventable risk factor but the contribution of specific occupations to COPD risk in a general population is uncertain. Our aim was to investigate the association of COPD with occupation in the UK population. Methods In 2006–2010, the UK Biobank cohort recruited 502u2005649 adults aged 40–69u2005years. COPD cases were identified by prebronchodilator forced expiratory volume in 1u2005s/forced vital capacity<lower limit of normal according to American Thoracic Society (ATS)/ European Respiratory Society (ERS) guidelines. Current occupations were coded using the Standard Occupational Classification (SOC) 2000. Prevalence ratios (PRs) and 95% CIs of COPD for each SOC-coded job were estimated using a robust Poisson model adjusted for sex, age, recruitment centre and lifetime tobacco smoking. Analyses restricted to never-smokers and non-asthmatics were also performed. Results Of the 353 occupations reported by 228u2005614 current working participants, several showed significantly increased COPD risk. Those at highest COPD risk were seafarers (PR=2.64; 95% CI 1.59 to 4.38), coal mine operatives (PR=2.30; 95% CI 1.00 to 5.31), cleaners (industrial: PR=1.96; 95% CI 1.16 to 3.31 and domestic: PR=1.43; 95% CI 1.28 to 1.59), roofers/tilers (PR=1.86; 95% CI 1.29 to 2.67), packers/bottlers/canners/fillers (PR=1.60; 95% CI 1.15 to 2.22), horticultural trades (PR=1.55; 95% CI 0.97 to 2.50), food/drink/tobacco process operatives (PR=1.46; 95% CI 1.11 to 1.93), floorers/wall tilers (PR=1.41; 95% CI 1.00 to 2.00), chemical/related process operatives (PR=1.39; 95% CI 0.98 to 1.97), postal workers/couriers (PR=1.35; 95% CI 1.15 to 1.59), labourers in building/woodworking trades (PR=1.32; 95% CI 1.04 to 1.68), school mid-day assistants (PR=1.32; 95% CI 1.01 to 1.74) and kitchen/catering assistants (PR=1.30; 95% CI 1.10 to 1.53). Associations were similar in analyses restricted to never-smokers and non-asthmatics. Conclusions Selected occupations are associated with increased COPD risk in a large cross-sectional population-based UK study. Further analyses should confirm the extent to which these associations reflect exposures still of concern and where strengthened preventive action may be needed.

Population Attributable and Preventable Fractions: Cancer Risk Factor Surveillance, and Cancer Policy Projection

The proportions of new cancer cases and deaths that are caused by exposure to risk factors and that could be prevented are key statistics for public health policy and planning. This paper summarizes the methodologies for estimating, challenges in the analysis of, and utility of, population attributable and preventable fractions for cancers caused by major risk factors such as tobacco smoking, dietary factors, high body fat, physical inactivity, alcohol consumption, infectious agents, occupational exposure, air pollution, sun exposure, and insufficient breastfeeding. For population attributable and preventable fractions, evidence of a causal relationship between a risk factor and cancer, outcome (such as incidence and mortality), exposure distribution, relative risk, theoretical-minimum-risk, and counterfactual scenarios need to be clearly defined and congruent. Despite limitations of the methodology and the data used for estimations, the population attributable and preventable fractions are a useful tool for public health policy and planning.

The future excess fraction of occupational cancer among those exposed to carcinogens at work in Australia in 2012

BACKGROUNDnStudies in other countries have generally found approximately 4% of current cancers to be attributable to past occupational exposures. This study aimed to estimate the future burden of cancer resulting from current occupational exposures in Australia.nnnMETHODSnThe future excess fraction method was used to estimate the future burden of occupational cancer (2012-2094) among the proportion of the Australian working population who were exposed to occupational carcinogens in 2012. Calculations were conducted for 19 cancer types and 53 cancer-exposure pairings, assuming historical trends and current patterns continued to 2094.nnnRESULTSnThe cohort of 14.6 million Australians of working age in 2012 will develop an estimated 4.8 million cancers during their lifetime, of which 68,500 (1.4%) are attributable to occupational exposure in those exposed in 2012. The majority of these will be lung cancers (n=26,000), leukaemias (n=8000), and malignant mesotheliomas (n=7500).nnnCONCLUSIONSnA significant proportion of future cancers will result from occupational exposures. This estimate is lower than previous estimates in the literature; however, our estimate is not directly comparable to past estimates of the occupational cancer burden because they describe different quantities - future cancers in currently exposed versus current cancers due to past exposures. The results of this study allow us to determine which current occupational exposures are most important, and where to target exposure prevention.

The burden of occupationally-related cutaneous malignant melanoma in Britain due to solar radiation

Background:Increasing evidence highlights the association of occupational exposure and cutaneous malignant melanoma (CMM). We estimated the burden of CMM and total skin cancer burden in Britain due to occupational solar radiation exposure.Methods:Attributable fractions (AF) and numbers were estimated for CMM mortality and incidence using risk estimates from the published literature and national data sources for proportions exposed. We extended existing methods to account for the exposed population age structure.Results:The estimated total AF for CMM is 2.0% (95% CI: 1.4–2.7%), giving 48 (95% CI: 33–64) deaths in (2012) and 241 (95% CI: 168–325) registrations (in 2011) attributable to occupational exposure to solar radiation. Higher exposure and larger numbers exposed led to much higher numbers for men than women. Industries of concern are construction, agriculture, public administration and defence, and land transport.Conclusions:These results emphasise the urgent need to develop appropriate strategies to reduce this burden.

A behavioural change package to prevent hand dermatitis in nurses working in the national health service (the SCIN trial): study protocol for a cluster randomised controlled trial

BackgroundHand dermatitis can be a serious health problem in healthcare workers. While a range of skin care strategies and policy directives have been developed in recent years to minimise the risk, their effectiveness and cost-effectiveness remain unclear. Evidence now suggests that psychological theory can facilitate behaviour change with respect to improved hand care practices. Therefore, we will test the hypothesis that a behavioural change intervention to improve hand care, based on the Theory of Planned Behaviour and implementation intentions, coupled with provision of hand moisturisers, can produce a clinically useful reduction in the occurrence of hand dermatitis, when compared to standard care, among nurses working in the UK National Health Service (NHS) who are particularly at risk. Secondary aims will be to assess impacts on participants’ beliefs and behaviour regarding hand care. In addition, we will assess the cost-effectiveness of the intervention in comparison with normal care.Methods/DesignWe will conduct a cluster randomised controlled trial at 35 NHS hospital trusts/health boards/universities, focussing on student nurses with a previous history of atopic disease or hand eczema and on nurses in intensive care units.Nurses at ‘intervention-light’ sites will be managed according to what would currently be regarded as best practice, with provision of an advice leaflet about optimal hand care to prevent hand dermatitis and encouragement to contact their occupational health (OH) department early if hand dermatitis occurs. Nurses at ‘intervention-plus’ sites will additionally receive a behavioural change programme (BCP) with on-going active reinforcement of its messages, and enhanced provision of moisturising cream.The impact of the interventions will be compared using information collected by questionnaires and through standardised photographs of the hands and wrists, collected at baseline and after 12xa0months follow-up. In addition, we will assemble relevant economic data for an analysis of costs and benefits, and collect information from various sources to evaluate processes.Statistical analysis will be by multi-level regression modelling to allow for clustering by site, and will compare the prevalence of outcome measures at follow-up after adjustment for values at baseline. The principal outcome measure will be the prevalence of visible hand dermatitis as assessed by the study dermatologists. In addition, several secondary outcome measures will be assessed.DiscussionThis trial will assess the clinical and cost effectiveness of an intervention to prevent hand dermatitis in nurses in the United Kigdom.Trial registrationISRCTN53303171: date of registration, 21 June 2013.

Estimating the burden of occupational cancer: assessing bias and uncertainty

Background and objectives We aimed to estimate credibility intervals for the British occupational cancer burden to account for bias uncertainty, using a method adapted from Greenland’s Monte Carlo sensitivity analysis. Methods The attributable fraction (AF) methodology used for our cancer burden estimates requires risk estimates and population proportions exposed for each agent/cancer pair. Sources of bias operating on AF estimator components include non-portability of risk estimates, inadequate models, inaccurate data including unknown cancer latency and employment turnover and compromises in using the available estimators. Each source of bias operates on a component of the AF estimator. Independent prior distributions were estimated for each bias, or graphical sensitivity analysis was used to identify plausible distribution ranges for the component variables, with AF recalculated following Monte Carlo repeated sampling from these distributions. The methods are illustrated using the example of lung cancer due to occupational exposure to respirable crystalline silica in men. Results Results are presented graphically for a hierarchy of biases contributing to an overall credibility interval for lung cancer and respirable crystalline silica exposure. An overall credibility interval of 2.0% to 16.2% was estimated for an AF of 3.9% in men. Choice of relative risk and employment turnover were shown to contribute most to overall estimate uncertainty. Bias from using an incorrect estimator makes a much lower contribution. Conclusions The method illustrates the use of credibility intervals to indicate relative contributions of important sources of uncertainty and identifies important data gaps; results depend greatly on the priors chosen.