Does living near heavy industry cause lung cancer in women? A case-control study using life grid interviews.

BACKGROUND: The incidence of lung cancer among women is high in the highly industrialised area of Teesside in north-east England. Previous research has implicated industrial pollution as a possible cause. A study was undertaken to investigate whether prolonged residence close to heavy industry is associated with lung cancer among women in Teesside. METHODS: Two hundred and four women aged <80 years with incident primary lung cancer and 339 age matched community controls were recruited to a population based case-control study. Life course residential, occupational, and active and passive smoking histories were obtained using an interviewer administered questionnaire. RESULTS: The age adjusted odds ratio (OR) for lung cancer among people living >25 years v 0 years near (within 0-5 km) heavy industry in Teesside was 2.13 (95% CI 1.34 to 3.38). After adjustment for confounding factors the OR was 1.83 (95% CI 0.82 to 4.08) for >25 years or 1.10 (95% CI 0.96 to 1.26) for an additional 10 years living near industry. ORs were similar after residence near heavy industry outside Teesside was also included, and when latency was allowed for by disregarding residential exposures within the last 20 years. Adjustment for active smoking had the greatest effect on the OR. CONCLUSIONS: This population based study using life grid interviews for life course exposure assessment has addressed many deficiencies in the design of previous studies. The findings support those in most of the international literature of a modestly raised risk of lung cancer with prolonged residence close to heavy industry, although the confidence intervals were wide. The effect of air pollution on the incidence of lung cancer merits continued study.

Factors associated with non-participation in a physical activity promotion trial.

BACKGROUND: Non-participation can bias outcome in intervention studies of physical activity. OBJECTIVES: To compare characteristics, knowledge and attitudes to physical activity in participants and non-participants of a physical activity intervention trial in primary care. STUDY DESIGN: Cross-sectional survey. METHODS: Patients aged 40-64 years were recruited opportunistically during surgery visits in an inner city general practice in Newcastle upon Tyne, UK. Attitudes to physical activity, views of its health benefits, and barriers to participation were elicited in interviews with participants, and by postal questionnaire from non-participants. Data held by general practitioners were used to compare anthropometry and lifestyle between groups. RESULTS: Of 842 eligible patients, 276 (33%) refused outright (non-volunteers) and 566 volunteered for the intervention study, of which 353 (42%) attended a baseline assessment and 213 (25%) subsequently defaulted. The initial refusal rate was higher amongst men, smokers and those with addresses in more deprived areas. The response rate to the postal survey of non-volunteers was 45%. Compared with participants, the non-volunteers were more likely to be an adult carer and to report poorer health, and were less likely to have had higher education or to have children living at home. Far more non-volunteers considered that they already did enough exercise to maintain health. Non-volunteers had slightly less knowledge of the benefits of physical activity; attached far less importance to it in maintaining health; were more likely to cite 'fear of leaving their home unattended', 'do not enjoy exercise' and 'poor health' as barriers to exercise; and were less likely to cite 'no one to exercise with' as a barrier to exercise. CONCLUSION: Recruitment of 'hard to engage' individuals requires careful phrasing of the message to focus on their personal goals and to address gaps in their knowledge about physical activity and the principal barriers they perceive. Differential uptake across population subgroups could lead to a widening of health inequalities.

Does long term residency near industry have an impact on the body burden of polychlorinated dibenzo-p-dioxins, furans, and polychlorinated biphenyls in older women?

BACKGROUND: For the retrospective study of environment and health linkages biomarkers of exposure are required. Polychlorinated dibenzo-dioxins and furans (PCDD/F) and polychlorinated biphenyls (PCBs) have been useful markers in some settings. This is the first study of PCDD/F body burden in a population based sample from the UK. AIMS AND METHODS: The authors aimed to investigate whether long term residents close to a heavy chemical industrial complex (Teesside, UK) had a higher body burden and distinct pattern of PCDD/F and PCBs. We measured current levels of PCDD/F and PCBs in a population based sample of older women (mean 64 years, range 42-79 years). Forty women were recruited, 20 living near (zone A: 0.1-2.7 km) and 20 distant (zone C: 5-40 km) from industry during 2000-03. The authors ascertained occupational exposure to lung carcinogens, residential history, consumption of local produce, breast feeding, diet, and height and weight. RESULTS: The mean body burden measured on lipid basis in ng/kg for the whole sample was: WHO-TEQ (PCDD/Fs): 29.9, 2378TCDD: 4.0, PCB 118:16200, PCB156: 13100. Body burdens were similar to others reported from industrialised countries, except that mean 2378TCDD was slightly higher. Mean ages, body mass index, and lifelong dietary patterns were similar in both zones. The authors found no significant difference in mean body burden levels between zones A and C before or after adjustment for covariates. All congener patterns were consistent with an urban background pattern, and there was no significant difference between congener compositions in the two zones. The TCDD body burden increased with age with accelerated increments above age 70. CONCLUSION: Long term residency near heavy and chemical industry did not have an effect on women's body burden of PCDD/Fs and PCBs on Teesside, UK. The body burden of PCDD/F and PCBs was not a suitable biomarker for chronic, non-occupational exposure to industrial air pollution.

Upper aerodigestive tract cancers in former employees at an iron and steel works.

Local concern about numbers of laryngeal cancer cases led to an investigation of the incidence of upper aerodigestive tract (UAT) cancer in an industrial cohort. Males (n = 11 470) who had been directly employed at an iron and steel works in northern England at any time between January 1960 and site closure in September 1983 were followed up for UAT cancers until December 1998. The incidence of UAT and laryngeal cancer was compared to the general population of the region via indirect standardization. Fifty-two members of the cohort developed a UAT cancer during 1960-1998. There were no more UAT cancers than expected [standardized incidence ratio = 97, 95% confidence interval (CI) = 72-127], but slightly more laryngeal cancers than expected (standardized incidence ratio = 118, 95% CI = 78-171), although this estimate was less precise. The lack of complete work histories meant that relationships between cancer incidence and length of service or job categories could not be explored.

Identifying industrial sites with potential for residential exposure to asbestos.

BACKGROUND: Non-occupational exposure to asbestos has been of increasing interest, but residential exposure to asbestos often focuses on a few high-profile asbestos users. This study aimed to identify industrial sites producing asbestos goods in a given area and time period. METHODS: A search of trade directories was carried out for industrial sites in West Yorkshire, England, where asbestos may have been used this century. RESULTS: A large number of factories with potential for residential exposure were found. A total of 269 factories in West Yorkshire used asbestos between 1900 and 1979, many for short periods only. CONCLUSIONS: Identification of potential sources of residential exposure to asbestos would have greatly underestimated their number if either only high-profile users or existing official listings had been used. Any consideration of asbestos use should aim to identify all users, not just the high-profile manufacturers.

An exploratory population-based case-control study of primary biliary cirrhosis.

Primary biliary cirrhosis (PBC) is a disease of unknown etiology, with unexplained geographical variation. Various exposures have been suggested as triggers for disease development-possibly in susceptible individuals, but the evidence was not always well founded. We therefore conducted a population-based case-control study in Northeast England to investigate these and other exposures. All cases incident during 1993 to 1995 in a defined area of Northeast England were identified, and age- and sex-matched population controls were identified from primary care population registers. Cases and controls were sent postal self-completion questionnaires covering medical history and lifestyle. Information was received from 100 cases and 223 controls. The familial tendency of PBC was found to be less marked than has been claimed: Only weak associations were found with other autoimmune diseases. Among factors considered previously, no significant associations were found with surgical procedures, events in pregnancy, past infections, vaccinations, and medications. No significant associations were found for previously unconsidered lifestyle factors (drinking alcohol, previous pets, or stressful events), but there was an unexpected association with past smoking (ever smoked: 76% in cases vs. 57% in controls, odds ratio 2.4; smoked for 20 years or more: 64% vs. 35%, odds ratio 3.5). There were also unexpected significant associations with psoriasis (13% in cases vs. 3% in controls, odds ratio 4.6) and eczema (3% in cases vs. 11% in controls, odds ratio 0. 13). These findings merit further investigation.

Cancer risk in primary biliary cirrhosis: a study in northern England.

BACKGROUND: Suggestions that breast cancer may be more common in patients with primary biliary cirrhosis (PBC) have been challenged. It has recently been proposed that total cancer rates may be higher in patients with PBC, as well as liver cancers. AIMS: To investigate these proposals on a strictly defined case series. SUBJECTS: A total of 769 prevalent or incident PBC patients with "definite" or "probable" disease detected in a defined area of the north-east of England during 1987-94. METHODS: Cancer events and deaths were identified by obtaining information from one or more of the following sources: Office for National Statistics (ONS) Central Registers, Regional Cancer Registry, and clinical case records. Standardised cancer incidence (SIR) and mortality ratios (SMR) were calculated using the local region as the standard population. RESULTS: There were 97 cancer events during 1987-96. SIR from cancer registrations for all cancers was 1.7 (95% confidence interval (CI) 1.3 to 2.2), for liver cancer was 74 (95% CI 32 to 146), and for breast cancer was 1.1 (95% CI 0.4 to 2.4). SMR for all cancers was 1. 8 (95% CI 1.4 to 2.4), for liver cancer was 39 (95% CI 20 to 68), and for breast cancer was 0.4 (95% 0.1 to 1.6). The results were similar after excluding the first year of follow up after PBC diagnosis. CONCLUSIONS: There was some evidence of a small increase in overall cancer incidence and mortality in PBC patients. With the exception of liver cancer, it is unlikely that there is a high excess incidence for PBC patients from any cancer at a particular site, and specifically breast cancer.

Mineral fibre analysis and routes of exposure to asbestos in the development of mesothelioma in an English region.

OBJECTIVES: To compare the concentrations of inorganic fibres in the lungs in cases of mesothelioma and controls: to determine whether concentrations of retained asbestos fibres differ with the different exposures identified from interview; and to investigate the existence of a cut off point in concentrations of asbestos fibres that indicates occupational exposure. METHODS: Case-control study; 147 confirmed cases of mesothelioma and 122 controls identified from deaths occurring in four districts of Yorkshire between 1979 and 1991. Surviving relatives were interviewed to determine lifetime exposure history to asbestos. Mineral fibre analysis was carried out on lung tissue from postmortem examinations. RESULTS: Odds on high concentrations of retained asbestos fibres were greater in cases than controls. After excluding subjects with occupational and paraoccupational exposure, the odds on high concentrations were still greater in cases than controls, but only significantly so for amphiboles. There was only a weak relation between probability of occupational exposure to asbestos and concentrations of retained asbestos fibres, and no significant difference in fibre concentrations was found between subjects who had been exposed to asbestos through different routes: these comparisons were only based on small groups. There was considerable overlap in concentrations of retained asbestos fibres between cases and controls with and without histories of occupational exposure. CONCLUSIONS: The study has confirmed previous results of higher concentrations of asbestos fibres in cases than controls, and has shown that this is still found in subjects with little evidence of occupational and para-occupational exposure. The overlap in concentrations of retained asbestos for different groups of subjects did not suggest a clear cut of value.

Impact of clinical practice guidelines on clinicians' behaviour: tonsillectomy in children.

OBJECTIVE: This study was conducted to assess the extent to which developing and implementing clinical practice guidelines for listing children for tonsillectomy (with or without adenoidectomy) influenced the behaviour of participating ENT surgeons. METHOD: A before and after study in which the intervention (the development and dissemination of local practice guidelines) was introduced sequentially into different hospitals and surgical practice. The study was conducted in four ear, nose, and throat surgical services in the North of England, with 16 consultant ENT surgeons and their junior staff on 1190 children aged 0 to 14 years who were judged, prior to consultation with an ENT surgeon, to have been referred for throat-related problems for which tonsillectomy was one possible treatment option were included in the study. Decision reached by surgeons and proportion of decisions that complied with new guidelines. RESULTS: Of the clinical decisions to list children for tonsillectomy taken before introduction of locally agreed guidelines, 73% (486/660) conformed to the criteria in the subsequent guidelines, 15% (97/660) did not, and in 12% (77/660), it was impossible to judge. After the intervention, the corresponding figures were 73% (386/530), 14% (73/53), and 13% (71/530), respectively. When decisions were taken to break the guidelines, this was more often to list for tonsillectomy when it was not indicated--83% (141/170)--than to withhold tonsillectomy when it was indicated--17% (29/170). The aspects of guidelines that were breached in decisions to carry out tonsillectomy were: the age of the child was younger than the guidelines recommended--54% (75/141); there had been fever attacks of tonsillitis than the guidelines recommended--22% (32/141); and there were "significant" symptoms not included in the guidelines--20% (29/141). CONCLUSIONS: In spite of strong evidence to the contrary, local guidelines were formulated at a level that the majority of surgeons already attained. Guideline development and implementation, therefore, had very little impact on clinical practice. The process of local formulation of guidelines was not sufficient to achieve change toward evidence-based practice; clinical preference proved to be quite intractable. There is a need to enhance the ability of clinicians in the assessment and interpretation of research evidence. Previous work has emphasized the need to explore factors that influence clinical behaviour toward evidence-based practice. Our study suggests the need for more research into why clinicians continue to follow clinical preference even when invited to base agreed local clinical policies on evidence.

Computer simulation to estimate the effectiveness of carotid endarterectomy.

OBJECTIVES: To investigate the benefit of carotid endarterectomy relative to medical treatment, by comparing the outcome for different groups of patients following transient ischaemic attacks. METHODS: A Markov model was used to describe the survival and quality of life of patients treated for a transient ischaemic attack. The benefit is measured in terms of quality adjusted life months (QALMs). The outcome was estimated using a computer simulation with parameters based on published studies on the probability of events following treatment. The benefit of carotid endarterectomy was explored using a baseline set of parameters and a sensitivity analysis. RESULTS: The baseline scenario of a 65-year-old male patient with the model factors set at an intermediate level showed a benefit for surgery of 3 QALMs compared with medical treatment alone. The sensitivity analysis showed that the most favourable combination of factors had a benefit of 13.4 QALMs and the least favourable a loss of 2 QALMs. Of all 128 factor combinations, 79.9% showed a benefit for surgery, 5.5% showed equal benefit, and 15.6% showed a benefit for medical treatment. CONCLUSIONS: Computer simulations have the potential for deriving estimates of benefit for different patient groups from the results of clinical trials. Combined with reliable information on costs, the technique could also demonstrate variations in cost-effectiveness for these groups. For patients following a transient ischaemic attack, the results from this simulation and limited cost information suggest that carotid endarterectomy is unlikely to be a cost-effective intervention in the UK for many patient groups despite a reduction in the risk of stroke.

Routes of asbestos exposure and the development of mesothelioma in an English region.

OBJECTIVES: To investigate the contribution of exposure to asbestos through different routes in the development of mesothelioma. METHODS: Case-control study. 185 confirmed cases of mesothelioma and 160 controls were identified, when death had occurred between 1979 and 1991 in four health districts in Yorkshire. The surviving relatives were interviewed to ascertain lifetime exposure to asbestos. Adjusted odds ratios (ORs) of exposure to asbestos (through occupational, paraoccupational, and residential routes) were calculated for cases and were compared with controls. RESULTS: Likely or possible occupational exposure to asbestos was more common in cases than in controls (OR 5.6, 95% confidence interval (95% CI) 3.1 to 10.1). After excluding those with likely or possible occupational exposure, likely or possible paraoccupational exposure was more common in cases than controls (OR 5.8, 95% CI 1.8 to 19.2). Only six cases of mesothelioma were identified as being solely exposed to asbestos through their residence, compared with nine controls. The OR for residential exposure to asbestos varied between 1.5 and 6.6, depending on which potential industrial sources were included, but the 95% CIs were so wide that slightly reduced or greatly increased odds comparing cases with controls could not be excluded. CONCLUSION: Study results support previous evidence that occupational and paraoccupational exposure to asbestos is associated with developing mesothelioma. Despite a rigorous search, purely residential exposure seemed to account for only 3% of identified cases. No firm conclusion can be drawn about the risks from residential exposure alone, as many of the study subjects could also have been occupationally or paraoccupationally exposed to asbestos.

Late-onset idiopathic scoliosis in children six to fourteen years old. A cross-sectional prevalence study.

We performed a point-prevalence survey of 15,799 children, six to fourteen years old, who formed part of a prospective longitudinal study. Our purpose was to detect the prevalence of scoliosis and to investigate associated factors. On the basis of the initial screening, 934 children (5.9 per cent) were referred for additional clinical and radiographic examinations; 896 children returned for this second evaluation. A lateral spinal curve with a Cobb angle of more than 5 degrees was seen in 431 children (2.7 per cent of the 15,799 children). Only seventy-six children (0.5 per cent) had a curve that met our definition of idiopathic scoliosis (a curve of more than 10 degrees with concordant apical rotation). The point-prevalence rate was higher in girls, and it increased with age. The rate was 0.1 per cent (four of 5246) in the age-group of six to eight years, 0.3 per cent (sixteen of 5831) in the age-group of nine to eleven years, and 1.2 per cent (fifty-six of 4722) in the age-group of twelve to fourteen years old. With allowance for the fact that different definitions of idiopathic scoliosis have been used in earlier studies, our results suggest that the natural history of idiopathic scoliosis may be becoming more benign spontaneously.

Spatial distribution of muscle necrosis in biopsies from patients with inflammatory muscle disorders.

Muscle biopsies from 56 patients with polymyositis (PM), juvenile dermatomyositis (JDM) and adult dermatomyositis (ADM) were investigated using a range of quantitative histological techniques. The objective was to present data on the extent and distribution of muscle fibre degeneration in these patients and to determine whether these data were compatible with postulated mechanisms of fibre injury. Atrophy of one or more of the major fibre types was found in 45/56 biopsies but there was no evidence that particular patterns of type-specific atrophy were characteristic of any individual disease group. However, selective atrophy and/or necrosis of perifascicular fibres was much more common in JDM patients than in ADM or PM groups. In virtually all biopsies where abnormalities of the microvasculature were apparent (7/8 JDM biopsies, 4/13 ADM biopsies and 5/33 PM biopsies) the distribution of acute muscle necrosis was found to be non-random (clustered). However, a substantial proportion of biopsies in the PM group showed clustering of necrotic fibres in the absence of evidence of vascular involvement. This finding suggests that non-random targetting of muscle fibres by effector cells may occur.

The IgG subclass distribution of thyroglobulin antibody synthesized in culture.

Thyroglobulin autoantibodies synthesized by Hashimoto lymphocytes in culture and present in serum have been analysed in terms of their IgG subclass distribution. The autoantibodies produced in vitro were frequently IgG4 or IgG1, whether pokeweed mitogen or Epstein-Barr virus was used to stimulate the cultures, and the subclass distribution of these thyroglobulin antibodies was similar to that observed in the patients' serum. It appears therefore that the antibodies synthesized in vitro in response to polyclonal B-cell activators resemble those produced in vivo, and it seems likely that both pokeweed mitogen and Epstein-Barr virus influence the same B-cell precursors of autoantibody-synthesizing cells, albeit by different mechanisms.