Workplace interventions to reduce the risk of SARS-CoV-2 infection outside of healthcare settings.

BACKGROUND: Although many people infected with SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) experience no or mild symptoms, some individuals can develop severe illness and may die, particularly older people and those with underlying medical problems. Providing evidence-based interventions to prevent SARS-CoV-2 infection has become more urgent with the potential psychological toll imposed by the coronavirus disease 2019 (COVID-19) pandemic. Controlling exposures to occupational hazards is the fundamental method of protecting workers. When it comes to the transmission of viruses, workplaces should first consider control measures that can potentially have the most significant impact. According to the hierarchy of controls, one should first consider elimination (and substitution), then engineering controls, administrative controls, and lastly, personal protective equipment. This is the first update of a Cochrane review published 6 May 2022, with one new study added. OBJECTIVES: To assess the benefits and harms of interventions in non-healthcare-related workplaces aimed at reducing the risk of SARS-CoV-2 infection compared to other interventions or no intervention. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, Web of Science Core Collections, Cochrane COVID-19 Study Register, World Health Organization (WHO) COVID-19 Global literature on coronavirus disease, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform, and medRxiv to 13 April 2023. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and non-randomised studies of interventions. We included adult workers, both those who come into close contact with clients or customers (e.g. public-facing employees, such as cashiers or taxi drivers), and those who do not, but who could be infected by coworkers. We excluded studies involving healthcare workers. We included any intervention to prevent or reduce workers' exposure to SARS-CoV-2 in the workplace, defining categories of intervention according to the hierarchy of hazard controls (i.e. elimination; engineering controls; administrative controls; personal protective equipment). DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were incidence rate of SARS-CoV-2 infection (or other respiratory viruses), SARS-CoV-2-related mortality, adverse events, and absenteeism from work. Our secondary outcomes were all-cause mortality, quality of life, hospitalisation, and uptake, acceptability, or adherence to strategies. We used the Cochrane RoB 2 tool to assess risk of bias, and GRADE methods to evaluate the certainty of evidence for each outcome. MAIN RESULTS: We identified 2 studies including a total of 16,014 participants. Elimination-of-exposure interventions We included one study examining an intervention that focused on elimination of hazards, which was an open-label, cluster-randomised, non-inferiority trial, conducted in England in 2021. The study compared standard 10-day self-isolation after contact with an infected person to a new strategy of daily rapid antigen testing and staying at work if the test is negative (test-based attendance). The trialists hypothesised that this would lead to a similar rate of infections, but lower COVID-related absence. Staff (N = 11,798) working at 76 schools were assigned to standard isolation, and staff (N = 12,229) working at 86 schools were assigned to the test-based attendance strategy. The results between test-based attendance and standard 10-day self-isolation were inconclusive for the rate of symptomatic polymerase chain reaction (PCR)-positive SARS-CoV-2 infection (rate ratio (RR) 1.28, 95% confidence interval (CI) 0.74 to 2.21; 1 study; very low-certainty evidence). The results between test-based attendance and standard 10-day self-isolation were inconclusive for the rate of any PCR-positive SARS-CoV-2 infection (RR 1.35, 95% CI 0.82 to 2.21; 1 study; very low-certainty evidence). COVID-related absenteeism rates were 3704 absence days in 566,502 days-at-risk (6.5 per 1000 working days) in the control group and 2932 per 539,805 days-at-risk (5.4 per 1000 working days) in the intervention group (RR 0.83, 95% CI 0.55 to 1.25). We downgraded the certainty of the evidence to low due to imprecision. Uptake of the intervention was 71% in the intervention group, but not reported for the control intervention. The trial did not measure our other outcomes of SARS-CoV-2-related mortality, adverse events, all-cause mortality, quality of life, or hospitalisation. We found seven ongoing studies using elimination-of-hazard strategies, six RCTs and one non-randomised trial. Administrative control interventions We found one ongoing RCT that aims to evaluate the efficacy of the Bacillus Calmette-Guérin (BCG) vaccine in preventing COVID-19 infection and reducing disease severity. Combinations of eligible interventions We included one non-randomised study examining a combination of elimination of hazards, administrative controls, and personal protective equipment. The study was conducted in two large retail companies in Italy in 2020. The study compared a safety operating protocol, measurement of body temperature and oxygen saturation upon entry, and a SARS-CoV-2 test strategy with a minimum activity protocol. Both groups received protective equipment. All employees working at the companies during the study period were included: 1987 in the intervention company and 1798 in the control company. The study did not report an outcome of interest for this systematic review. Other intervention categories We did not find any studies in this category. AUTHORS' CONCLUSIONS: We are uncertain whether a test-based attendance policy affects rates of PCR-positive SARS-CoV-2 infection (any infection; symptomatic infection) compared to standard 10-day self-isolation amongst school and college staff. A test-based attendance policy may result in little to no difference in absenteeism rates compared to standard 10-day self-isolation. The non-randomised study included in our updated search did not report any outcome of interest for this Cochrane review. As a large part of the population is exposed in the case of a pandemic, an apparently small relative effect that would not be worthwhile from the individual perspective may still affect many people, and thus become an important absolute effect from the enterprise or societal perspective. The included RCT did not report on any of our other primary outcomes (i.e. SARS-CoV-2-related mortality and adverse events). We identified no completed studies on any other interventions specified in this review; however, eight eligible studies are ongoing. More controlled studies are needed on testing and isolation strategies, and working from home, as these have important implications for work organisations.

Exposure assessment for repeated sub-concussive head impacts in soccer: The HEalth and Ageing Data IN the Game of football (HEADING) study.

The purpose of this paper was to develop exposure estimates for repetitive sub-concussive head impacts (RSHI) for use in epidemiological analyses. We used a questionnaire to collect lifetime history of heading and other head contacts associated with training and playing football from 159 former footballers all members of the English professional football association. We used linear mixed effect regression with player as the random effect, to model the number of headers, blows to the head and head-to-head impacts as a function of potential exposure affecting factors, which were treated as the fixed effects. Exposure affecting factors included playing position, league, context of play (game vs training) and decade of play. Age at time of response to the questionnaire was also included in the models. In model results, playing position was important, with RSHIs being highest among defenders and lowest among goalkeepers. Players headed the ball more during games than in training, and when playing in amateur or youth leagues compared with semi-professional or professional leagues. The average number of reported head impacts declined linearly throughout the observation period (1949-2015). The derived final model for headers explained 43%, 9% and 36% of the between player, within player and total variance in exposure, respectively with good precision and predictive performance. These findings are generally in agreement with previously published results pointing towards the models forming a valid method for estimating exposure to RSHI among former footballers although some further external validation is still warranted.

A Systematic Review of Head Impacts and Acceleration Associated with Soccer.

Epidemiological studies of the neurological health of former professional soccer players are being undertaken to identify whether heading the ball is a risk factor for disease or premature death. A quantitative estimate of exposure to repeated sub-concussive head impacts would provide an opportunity to investigate possible exposure-response relationships. However, it is unclear how to formulate an appropriate exposure metric within the context of epidemiological studies. We have carried out a systematic review of the scientific literature to identify the factors that determine the magnitude of head impact acceleration during experiments and from observations during playing or training for soccer, up to the end of November 2021. Data were extracted from 33 experimental and 27 observational studies from male and female amateur players including both adults and children. There was a high correlation between peak linear and angular accelerations in the observational studies (p < 0.001) although the correlation was lower for the experimental data. We chose to rely on an analysis of maximum or peak linear acceleration for this review. Differences in measurement methodology were identified as important determinants of measured acceleration, and we concluded that only data from accelerometers fixed to the head provided reliable information about the magnitude of head acceleration from soccer-related impacts. Exposures differed between men and women and between children and adults, with women on average experiencing higher acceleration but less frequent impacts. Playing position appears to have some influence on the number of heading impacts but less so on the magnitude of the head acceleration. Head-to-head collisions result in high levels of exposure and thus probably risk causing a concussion. We concluded, in the absence of evidence to the contrary, that estimates of the cumulative number of heading impacts over a playing career should be used as the main exposure metric in epidemiological studies of professional players.

Determinants of Burnout among Teachers: A Systematic Review of Longitudinal Studies.

We aimed to review the determinants of burnout onset in teachers. The study was conducted according to the PROSPERO protocol CRD42018105901, with a focus on teachers. We performed a literature search from 1990 to 2021 in three databases: MEDLINE, PsycINFO, and Embase. We included longitudinal studies assessing burnout as a dependent variable, with a sample of at least 50 teachers. We summarized studies by the types of determinant and used the MEVORECH tool for a risk of bias assessment (RBA). The quantitative synthesis focused on emotional exhaustion. We standardized the reported regression coefficients and their standard errors and plotted them using R software to distinguish between detrimental and protective determinants. A qualitative analysis of the included studies (n = 33) identified 61 burnout determinants. The RBA showed that most studies had external and internal validity issues. Most studies implemented two waves (W) of data collection with 6-12 months between W1 and W2. Four types of determinants were summarized quantitatively, namely support, conflict, organizational context, and individual characteristics, based on six studies. This systematic review identified detrimental determinants of teacher exhaustion, including job satisfaction, work climate or pressure, teacher self-efficacy, neuroticism, perceived collective exhaustion, and classroom disruption. We recommend that authors consider using harmonized methods and protocols such as those developed in OMEGA-NET and other research consortia.

Migrant workers occupational health research: an OMEGA-NET working group position paper.

OBJECTIVE: The aims of the study were: (1) to clarify the definitions of "migrant" used in occupational health research; (2) to summarize migrant workers' industry sectors, occupations and employment conditions; (3) to identify the occupational health and safety services available to migrant workers; (4) to summarize work-related health problems found among migrant workers; (5) to identify the methodological challenges to research into occupational health of migrant workers; and (6) to recommend improvements in migrant occupational health research. METHODS: This position paper was prepared by researchers from several European countries and Australia, working within the EU COST Action OMEGA-NET. The paper drew on two recent systematic reviews on the occupational health of international migrant workers and other literature, and also identified uncertainties and gaps in the research literature. Migrants may, for example, be temporary or permanent, moving for specific jobs migrants or other reasons. Their ethnicity and language capabilities will affect their work opportunities. RESULTS: The occupational health literature seldom adequately identifies the heterogeneity or characteristics of the migrant group being studied. Migrants tend to work in more physically and mentally demanding environments with higher exposures than native workers. Migrants tend to have an increased risk of physical and mental ill health, but less access to health care services. This has been demonstrated recently by high rates of COVID-19 and less access to health care. There have been a number of cross-sectional studies of migrant health but few long-term cohort studies were identified. Other study designs, such as registry-based studies, surveys and qualitative studies may complement cross-sectional studies. Mixed-methodology studies would be valuable in research on migrants' occupational health. Language and lack of trust are barriers to migrant research participation. CONCLUSION: Targeted research, especially longitudinal, identifying how these economically important but often-vulnerable workers can be best assisted is needed. Researchers should identify the characteristics of the migrant workers that they are studying including visa/migration circumstances (temporary, permanent, undocumented), racial and ethnic characteristics, existing skills and language abilities.

Concussion and long-term cognitive function among rugby players-The BRAIN Study.

OBJECTIVE: The BRAIN Study was established to assess the associations between self-reported concussions and cognitive function among retired rugby players. METHODS: Former elite-level male rugby union players (50+ years) in England were recruited. Exposure to rugby-related concussion was collected using the BRAIN-Q tool. The primary outcome measure was the Preclinical Alzheimer Cognitive Composite (PACC). Linear regressions were conducted for the association between concussion and PACC score, adjusting for confounders. RESULTS: A total of 146 participants were recruited. The mean (standard deviation) length of playing career was 15.8 (5.4) years. A total of 79.5% reported rugby-related concussion(s). No association was found between concussion and PACC (ß -0.03 [95% confidence interval (CI): -1.31, 0.26]). However, participants aged 80+ years reporting 3+ concussions had worse cognitive function than those without concussion (ß -1.04 [95% CI: -1.62, -0.47]). CONCLUSIONS: Overall there was no association between concussion and cognitive function; however, a significant interaction with age revealed an association in older participants.

Predictors of Occupational Burnout: A Systematic Review.

We aimed to review occupational burnout predictors, considering their type, effect size and role (protective versus harmful), and the overall evidence of their importance. MEDLINE, PsycINFO, and Embase were searched from January 1990 to August 2018 for longitudinal studies examining any predictor of occupational burnout among workers. We arranged predictors in four families and 13 subfamilies of homogenous constructs. The plots of z-scores per predictor type enabled graphical discrimination of the effects. The vote-counting and binomial test enabled discrimination of the effect direction. The size of the effect was estimated using Cohen's formula. The risk of bias and the overall evidence were assessed using the MEVORECH and GRADE methods, respectively. Eighty-five studies examining 261 predictors were included. We found a moderate quality of evidence for the harmful effects of the job demands subfamily (six predictors), and negative job attitudes, with effect sizes from small to medium. We also found a moderate quality of evidence for the protective effect of adaptive coping (small effect sizes) and leisure (small to medium effect sizes). Preventive interventions for occupational burnout might benefit from intervening on the established predictors regarding reducing job demands and negative job attitudes and promoting adaptive coping and leisure.

Challenges to and facilitators of occupational epidemiology research in the UK.

This study investigated the challenges and facilitators of occupational epidemiology (OE) research in the UK, and evaluated the impact of these challenges. Semi-structured in-depth interviews with leading UK-based OE researchers, and a survey of UK-based OE researchers were conducted. Seven leading researchers were interviewed, and there were 54 survey respondents. Key reported challenges for OE were diminishing resources during recent decades, influenced by social, economic and political drivers, and changing fashions in research policy. Consequently, the community is getting smaller and less influential. These challenges may have negatively affected OE research, causing it to fail to keep pace with recent methodological development and impacting its output of high-quality research. Better communication with, and support from other researchers and relevant policy and funding stakeholders was identified as the main facilitators to OE research. Many diseases were initially discovered in workplaces, as these make exceptionally good study populations to accurately assess exposures. Due to the decline of manufacturing industry, there is a perception that occupational diseases are now a thing of the past. Nevertheless, new occupational exposures remain under-evaluated and the UK has become reliant on overseas epidemiology. This has been exacerbated by the decline in the academic occupational medicine base. Maintaining UK-based OE research is hence necessary for the future development of occupational health services and policies for the UK workforce.

Editor's Choice - Role of Compression After Radiofrequency Ablation of Varicose Veins: A Randomised Controlled Trial☆.

OBJECTIVE: Post-procedure limb compression, hitherto routine following open varicose vein surgery, has been extended to endovenous procedures. However, no robust evidence exists to support this practice. Most of the previous studies have focused on the ideal duration of compression. This study evaluates the clinical and patient reported outcomes with and without post-procedure leg compression following radiofrequency ablation (RFA). METHODS: This single centre, prospective, non-inferiority randomised controlled trial recruited adult patients, into two groups (A: RFA with compression stocking for two weeks, B: RFA alone). The primary outcome was ultrasound determined target vein obliteration at 12 weeks. Secondary outcome measures included a Quality of Life (QoL) score [Aberdeen Varicose Vein Severity Score (AVSS) and Revised Venous Clinical Severity Score (RVCSS)], patient satisfaction, pain score, and complications. RESULTS: In total, 100 consecutive patients were recruited (A: 51; B: 49) classified as clinical class C2-C6 of the Clinical-Etiological-Anatomical-Pathophysiological (CEAP) classification. At 12 weeks the occlusion rate of the target vein was similar in both groups at 98% (n = 47) and 98% (n = 45), respectively (p = 1.0). There was no statistically significant difference in mean AVSS 6 vs. 5.0 (mean difference -1, 95% CI -2 - 3, p = .57) and mean RVCSS 3 vs. 4 (mean difference 1, 95% CI -1 - 2, p = .46) scores at 12 weeks. Comparable patient satisfaction scores were observed (p = .72) and pain score 2.0 vs. 2.0 (p = .92) were achieved in both groups. Two patients in each group developed deep vein thrombosis at two weeks follow up (p = 1.0 for above the knee and p = 1.0 for below the knee). CONCLUSION: The clinical and patient reported outcomes following RFA without compression are no worse than with compression. This trial supports the conclusion that the widely practised use of compression after RFA adds no clinical benefit for the patients. However, a much larger study, preferably a multicentre trial, may be required to confirm this conclusion.

Predicting Severe Infection and Effects of Hypogammaglobulinemia During Therapy With Rituximab in Rheumatic and Musculoskeletal Diseases.

OBJECTIVE: To evaluate predictors of serious infection events (SIEs) during rituximab (RTX) therapy and effects of hypogammaglobulinemia on SIE rates, and humoral response and its persistence after discontinuation of RTX in the treatment of rheumatic and musculoskeletal diseases (RMDs). METHODS: A retrospective longitudinal study of 700 RMD patients treated with RTX in a single center was conducted. Immunoglobulin levels were measured at baseline and at 4-6 months after each treatment cycle. Baseline predictors of SIEs were assessed using multivariable logistic regression; for RTX cycles 2-4, a mixed-effects logistic regression model was used. RESULTS: A total of 507 patients (72%) had rheumatoid arthritis, 94 (13%) had systemic lupus erythematosus, 49 (7%) had antineutrophil cytoplasmic antibody-associated vasculitis, and 50 (7%) had other RMDs. The number of SIEs recorded was 281 in 176 patients (9.8 per 100 person-years). Predictors of SIEs included non-RTX-specific comorbidities (previous history of SIE, cancer, chronic lung disease, diabetes mellitus, and heart failure), higher corticosteroid dose, and RTX-specific factors, including low IgG (<6 gm/liter) both at baseline and during treatment, RTX-associated neutropenia, higher IgM, and longer time to RTX re-treatment, but not B cell count or depletion status. Of 110 patients with low IgG, SIE rates were higher in those with low IgG at baseline (16.4 per 100 person-years) and in those who acquired low IgG during or after RTX treatment (21.3 per 100 person-years) versus those with normal IgG (9.7 per 100 person-years). Five of 8 patients (63%) had impaired humoral response to pneumococcus and hemophilus following vaccination challenge, and only 4 of 11 patients (36%) had IgG normalized after switching biologic disease-modifying antirheumatic drugs. CONCLUSION: Immunoglobulin levels should be monitored at baseline and before each RTX cycle to identify patients at risk of SIEs. Individualized risk-benefit assessment should be undertaken in those with lower IgG as this is a consistent SIE predictor and may increase infection profiles when RTX is switched to different therapies.

Does the Size of a Company Make a Difference in the Prevalence of Exposure to Asthmagens and in the Use of Respiratory Protective Equipment?

Introduction: About half of all workers in high-income countries work in small companies. However, regulatory bodies and researchers predominantly work with large companies because they are more convenient to study and easier to reach. We aimed to estimate the prevalence of exposure to asthmagens and the use of respiratory protective equipment (RPE) by company size. Methods: This analysis used data from the Australian Work Exposures Study-Asthma, a telephone survey which investigated exposure to 27 asthmagen groups. Results: Among 4844 respondents, 18.8, 19.9, 31.9, and 29.4% of workers reported working in micro (<5 employees), small (5-19 employees), medium (20-200 employees), and large (>200 employees) companies, respectively. Compared to workers in large companies, workers in micro, small, or medium companies had higher prevalence of exposure to most asthmagens and lesser use of RPE. Conclusion: Our results suggest that policy actions and regulatory measures should target micro/small companies in order to have the greatest effect.

The INTEROCC case-control study: risk of meningioma and occupational exposure to selected combustion products, dusts and other chemical agents.

BACKGROUND: Little is known about occupational risk factors for meningioma. OBJECTIVES: To study whether risk of meningioma is associated with several occupational exposures, including selected combustion products, dusts and other chemical agents. METHODS: The INTEROCC study was an international case-control study of brain cancer conducted in seven countries. Data collection by interview included lifetime occupational histories. A job exposure matrix was used to derive estimates of exposure for the 12 agents. ORs for ever versus never exposed and for exposure-response using duration of exposure and cumulative exposure were derived using conditional logistic regression stratified by sex, age group, country/region, adjusted for education. RESULTS: These analyses included 1906 cases and 5565 controls. For 11 of the 12 agents, no excess risk was found for ever exposed. For ever exposure to oil mists, an elevated OR of 1.57 (95% CI 1.10 to 2.22, 51 exposed cases) was found. Statistically significant exposure-response relationships were observed with cumulative exposure (p=0.01) and duration of exposure (p=0.04). Among women, there were also significant trends for cumulative and duration of exposure to asbestos and excesses in the highest exposure categories for formaldehyde. CONCLUSIONS: Most agents examined did not provoke excess risks of meningioma. The main finding from this study is that it is the first study to identify a statistical association between exposure to oil mists and meningioma. This may be a chance finding or could be due to confounding with iron exposure and further research is required to understand whether the relationship is causal.

Mortality Among Hardmetal Production Workers: UK Cohort and Nested Case-Control Studies.

OBJECTIVE: The aim of this study was to characterize the mortality at two hardmetal production factories in the United Kingdom as part of an international study. METHODS: Standardized mortality ratios (SMRs) were calculated on the basis of mortality rates for England and Wales, and local rates. A nested case-control study of lung cancer was undertaken. RESULTS: The cohort comprised 1538 workers, with tracing complete for 94.4%. All-cause mortality was statistically significantly low for all cancers and nonmalignant respiratory disease, and for lung cancer was nonsignificantly low. The SMR for lung cancer for maintenance workers was elevated, based on only six deaths. The odds ratio for lung cancer per year of exposure to hardmetal was 0.93 (0.76 to 1.13). CONCLUSIONS: In this small study, there is no evidence to support that working in the UK hardmetal manufacturing industry increased mortality from any cause including lung cancer.

Male Breast Cancer Incidence and Mortality Risk in the Japanese Atomic Bomb Survivors - Differences in Excess Relative and Absolute Risk from Female Breast Cancer.

BACKGROUND: There are well-known associations of ionizing radiation with female breast cancer, and emerging evidence also for male breast cancer. In the United Kingdom, female breast cancer following occupational radiation exposure is among that set of cancers eligible for state compensation and consideration is currently being given to an extension to include male breast cancer. OBJECTIVES: We compare radiation-associated excess relative and absolute risks of male and female breast cancers. METHODS: Breast cancer incidence and mortality data in the Japanese atomic-bomb survivors were analyzed using relative and absolute risk models via Poisson regression. RESULTS: We observed significant (p ≤ 0.01) dose-related excess risk for male breast cancer incidence and mortality. For incidence and mortality data, there are elevations by factors of approximately 15 and 5, respectively, of relative risk for male compared with female breast cancer incidence, the former borderline significant (p = 0.050). In contrast, for incidence and mortality data, there are elevations by factors of approximately 20 and 10, respectively, of female absolute risk compared with male, both statistically significant (p < 0.001). There are no indications of differences between the sexes in age/time-since-exposure/age-at-exposure modifications to the relative or absolute excess risk. The probability of causation of male breast cancer following radiation exposure exceeds by at least a factor of 5 that of many other malignancies. CONCLUSIONS: There is evidence of much higher radiation-associated relative risk for male than for female breast cancer, although absolute excess risks for males are much less than for females. However, the small number of male cases and deaths suggests a degree of caution in interpretation of this finding. Citation: Little MP, McElvenny DM. 2017. Male breast cancer incidence and mortality risk in the Japanese atomic bomb survivors - differences in excess relative and absolute risk from female breast cancer. Environ Health Perspect 125:223-229; http://dx.doi.org/10.1289/EHP151.

Mortality of a cohort of workers in Great Britain with blood lead measurements.

OBJECTIVES: We examined the mortality of a historic cohort of workers in Great Britain with measured blood lead levels (BLLs). METHODS: SMRs were calculated with the population of Great Britain as the external comparator. Trends in mortality with mean and maximum BLLs and assessed lead exposure were examined using Cox regression. RESULTS: Mean follow-up length among the 9122 study participants was 29.2 years and 3466 deaths occurred. For all causes and all malignant neoplasms, the SMRs were statistically significantly raised. For disease groups of a priori interest, the SMR was significantly raised for lung cancer but not for stomach, brain, kidney, bladder or oesophageal cancers. The SMR was not increased for non-malignant kidney disease but was borderline significantly increased for circulatory diseases, for ischaemic heart disease (IHD) and cerebrovascular disease (CVD). No significant trends with exposure were observed for the cancers of interest, but for circulatory diseases and IHD, there was a statistically significant trend for increasing HR with mean and maximum BLLs. CONCLUSIONS: This study found an excess of lung cancer, although the risk was not clearly associated with increasing BLLs. It also found marginally significant excesses of IHD and CVD, the former being related to mean and maximum BLLs. The finding for IHD may have been due to lead, but could also have been due to other dust exposure associated with lead exposure and possibly tobacco smoking. Further work is required to clarify this and the carcinogenicity of lead.

Research recommendations for selected IARC-classified agents.

OBJECTIVES: There are some common occupational agents and exposure circumstances for which evidence of carcinogenicity is substantial but not yet conclusive for humans. Our objectives were to identify research gaps and needs for 20 agents prioritized for review based on evidence of widespread human exposures and potential carcinogenicity in animals or humans. DATA SOURCES: For each chemical agent (or category of agents), a systematic review was conducted of new data published since the most recent pertinent International Agency for Research on Cancer (IARC) Monograph meeting on that agent. DATA EXTRACTION: Reviewers were charged with identifying data gaps and general and specific approaches to address them, focusing on research that would be important in resolving classification uncertainties. An expert meeting brought reviewers together to discuss each agent and the identified data gaps and approaches. DATA SYNTHESIS: Several overarching issues were identified that pertained to multiple agents; these included the importance of recognizing that carcinogenic agents can act through multiple toxicity pathways and mechanisms, including epigenetic mechanisms, oxidative stress, and immuno- and hormonal modulation. CONCLUSIONS: Studies in occupational populations provide important opportunities to understand the mechanisms through which exogenous agents cause cancer and intervene to prevent human exposure and/or prevent or detect cancer among those already exposed. Scientific developments are likely to increase the challenges and complexities of carcinogen testing and evaluation in the future, and epidemiologic studies will be particularly critical to inform carcinogen classification and risk assessment processes.

Simian virus 40 and mesothelioma in Great Britain.

BACKGROUND: Simian virus 40 (SV40) is a DNA virus that has been shown capable of infecting and transforming cells in various species. Laboratory studies have suggested that inoculation with SV40 is associated with various types of cancer, including mesothelioma. AIMS: To test the hypothesis, via an ecological analysis, that exposure to SV40 via contaminated polio vaccines is a risk factor for mesothelioma in humans. METHODS: Mesothelioma mortality rates in Great Britain for two birth cohorts likely to have been exposed to SV40 via poliovirus vaccination were compared with a birth cohort likely to be largely unexposed. RESULTS: There was some evidence for both males (P < 0.05) and females (P < 0.05) that the mesothelioma mortality rates were higher in the first exposed cohort: rate ratio (RR) = 2.4 [95% CI (confidence interval) 1.2-5.0] and RR = 3.7 (95% CI 1.0-14). However, in the second exposed cohort, mortality rates were elevated in females only, and the evidence was slightly less convincing (P = 0.055). CONCLUSION: Although the results for females show a reduction in the mesothelioma mortality rate coinciding with the introduction of the SV40-free Sabin polio vaccine, the absence of a similar result in males and of a priori biological evidence of a sex-specific SV40 effect, makes chance the most plausible interpretation of these findings.

Estimating the number of asbestos-related lung cancer deaths in Great Britain from 1980 to 2000.

INTRODUCTION: Inhalation of asbestos fibres is known to cause two main kinds of cancer-mesothelioma and lung cancer. While the vast majority of mesothelioma cases are generally accepted as being caused by asbestos, the proportion of asbestos-related lung cancers is less clear and cannot be determined directly because cases are not clinically distinguishable from those due to other causes. The aim of this study was to estimate the number of asbestos-related lung cancers among males by modelling their relative lung cancer mortality among occupations within Great Britain in terms of smoking habits, mesothelioma mortality (as an index of asbestos exposure) and occupation type (as a proxy for socio-economic factors). METHODS: Proportional mortality ratios for lung cancer and mesothelioma for the 20-year period from 1980 to 2000 (excluding 1981) were calculated for occupational groups. Smoking indicators were developed from three General Household Surveys carried out during the 1980s and 1990s. Poisson regression models were used to estimate the number of asbestos-related lung cancers by estimating the number of lung cancer deaths in each occupation assuming no asbestos exposure and subtracting this from the actual predicted number of lung cancer deaths. RESULTS: The effect of asbestos exposure in predicting lung cancer mortality was weak in comparison to smoking habits and occupation type. The proportion of current smokers in occupational groups and average age at which they started smoking were particularly important factors. Our estimate of the number of asbestos-related lung cancers was between two-thirds and one death for every mesothelioma death: equivalent to between 11 500 and 16 500 deaths during the time period studied. CONCLUSIONS: Asbestos-related lung cancer is likely to have accounted for 2-3% of all lung cancer deaths among males in Great Britain over the last two decades of the 20th century. Asbestos-related lung cancers are likely to remain an important component of the total number of lung cancer deaths in the future as part of the legacy of past asbestos exposures in occupational settings.