Recent trends in physician diagnosed COPD in women and men in the UK.

BACKGROUND: Recent trends in physician diagnosed chronic obstructive pulmonary disease (COPD) in the UK were estimated, with a particular focus on women. METHODS: A retrospective cohort of British patients with COPD was constructed from the General Practice Research Database (GPRD), a large automated database of UK general practice data. Prevalence and all-cause mortality rates by sex, calendar year, and severity of COPD, based on treatment only, were estimated from January 1990 to December 1997. RESULTS: A total of 50 714 incident COPD patients were studied, 23 277 (45.9%) of whom were women. From 1990 to 1997 the annual prevalence rates of physician diagnosed COPD in women rose continuously from 0.80% (95% CI 0.75 to 0.83) to 1.36% (95% CI 1.34 to 1.39), (p for trend <0.01), rising to the rate observed in men in 1990. Increases in the prevalence of COPD were observed in women of all ages; in contrast, a plateau was observed in the prevalence of COPD in men from the mid 1990s. All-cause mortality rates were higher in men than in women (106.8 versus 82.2 per 1000 person-years), with a consistently increased relative risk in men of 1.3 even after controlling for the severity of COPD. Significantly increased mortality rates were also observed in adults aged less than 65 years. The mean age at death was 76.5 years; patients with severe COPD died an average of three years before those with mild disease (p<0.01) and four years before the age and sex matched reference population. CONCLUSIONS: While prevalence rates of COPD in the UK seem to have peaked in men, they are continuing to rise in women. This trend, together with the ageing of the population and the long term cumulative effect of pack-years of smoking in women, is likely to increase the present burden of COPD in the UK.

Heterogeneity in systemic availability of ondansetron and granisetron following oral administration.

This open-label, randomized, two-way crossover study compared the relative heterogeneity in systemic availability of oral ondansetron and granisetron. It was conducted in 10 healthy male and 10 healthy female subjects aged 18 to 50 years. Following an overnight fast, each subject received 8 mg ondansetron and 1 mg granisetron. Treatments were separated by 7 days. Blood samples for drug assay were collected over a period of 36 h and variability in pharmacokinetic parameter estimates were assessed following standardization by their respective means. Granisetron showed significantly more variability than ondansetron in the three primary endpoints of the area under the curve extrapolated to infinite time, the area under the curve to the last quantifiable time point, and maximal concentration (p =.0032,.0037, and.0042, respectively). In one subject, concentrations of granisetron were detectable but below the lower limit of quantitation at any time point. The impact this variability may have on therapeutic efficacy is not clear. An apparent bimodal distribution in granisetron AUC infinite, which appeared to be related to smoking was observed. Because granisetron has been reported to be metabolized primarily by the cytochrome P-450 (CYP) 3A isozyme family in humans, it is possible that cigarette smoke could be an inducer of CYP3A or that CYP1A2, also implicated in the metabolism of granisetron and known to be induced by smoking, is more important in the biotransformation of granisetron than previously thought.

Lymphohaematopoietic malignancy around all industrial complexes that include major oil refineries in Great Britain.

OBJECTIVES: To examine the incidence of lymphohaematopoietic malignancy around industrial complexes that include major oil refineries in Great Britain after recent public and scientific concern of possible carcinogenic hazards of emissions from the petrochemical industry. METHODS: Small area study of the incidence of lymphohaematopoietic malignancies, 1974-91, within 7.5 km of all 11 oil refineries (grouped into seven sites) in Great Britain that were operational by the early 1970s and processed more than two million tonnes of crude oil in 1993. RESULTS: Combined analysis of data from all seven sites showed no significant (p < 0.05) increase in risk of these malignancies within 2 km or 7.5 km. Hodgkin's lymphoma, but no other malignancy, showed evidence (p = 0.02) of a decline in risk with distance from refineries, but there was an apparent deficit of cases of multiple myeloma near the refineries (p = 0.04). CONCLUSION: There was no evidence of association between residence near oil refineries and leukaemias, or non-Hodgkin's lymphoma. A weak positive association was found between risk of Hodgkin's disease and proximity to major petrochemical industry, and a negative association with multiple myeloma, which may be chance findings within the context of multiple statistical testing.

Risk of lung cancer associated with residential radon exposure in south-west England: a case-control study.

Studies of underground miners occupationally exposed to radon have consistently demonstrated an increased risk of lung cancer in both smokers and non-smokers. Radon exposure also occurs elsewhere, especially in houses, and estimates based on the findings for miners suggest that residential radon is responsible for about one in 20 lung cancers in the UK, most being caused in combination with smoking. These calculations depend, however, on several assumptions and more direct evidence on the magnitude of the risk is needed. To obtain such evidence, a case-control study was carried out in south-west England in which 982 subjects with lung cancer and 3185 control subjects were interviewed. In addition, radon concentrations were measured at the addresses at which subjects had lived during the 30-year period ending 5 years before the interview. Lung cancer risk was examined in relation to residential radon concentration after taking into account the length of time that subjects had lived at each address and adjusting for age, sex, smoking status, county of residence and social class. The relative risk of lung cancer increased by 0.08 (95% CI -0.03, 0.20) per 100 Bq m(-3) increase in the observed time-weighted residential radon concentration. When the analysis was restricted to the 484 subjects with lung cancer and the 1637 control subjects with radon measurements available for the entire 30-year period of interest, the corresponding increase was somewhat higher at 0.14 per 100 Bq m(-3) (95% CI 0.01, 0.29), although the difference between this group and the remaining subjects was not statistically significant. When the analysis was repeated taking into account uncertainties in the assessment of radon exposure, the estimated increases in relative risk per 100 Bq m(-3) were larger, at 0.12 (95% CI -0.05, 0.33) when all subjects were included and 0.24 (95% CI -0.01, 0.56) when limited to subjects with radon measurements available for all 30 years. These results are consistent with those from studies of residential radon carried out in other countries in which data on individual subjects have been collected. The combined evidence suggests that the risk of lung cancer associated with residential radon exposure is about the size that has been postulated on the basis of the studies of miners exposed to radon.

Cancer incidence and mortality around the Pan Britannica Industries pesticide factory, Waltham Abbey.

OBJECTIVES: To examine the incidence and mortality of cancer near the Pan Britannica Industries factory, Waltham Abbey, after reports of a possible cluster of all cancers and brain cancer in the vicinity. METHOD: Small area study of cancer incidence 1977-89, and mortality 1981-92, within a 7.5 km radius of the factory site. Postcoded cancer registrations and deaths in the study area were extracted from national data sets held by the Small Area Health Statistics Unit and compared with expected numbers computed by applying national rates stratified for age, sex, and deprivation to the local population (1981 and 1991 censuses). Observed/ expected (O/E) ratios were examined from 0-1 km and 0-7.5 km of the plant, and tests applied for a decline in relative risk with distance up to 7.5 km. RESULTS: There were 12,859 incidence cancers (1977-89) from 0-7.5 km (O/E ratio 1.04; 95% confidence interval (95% CI) 1.02 to 1.06) and 385 from 0-1 km (O/E 1.10; 1.00 to 1.22). There was an excess of skin melanoma from 0-1 km based on 11 cases (O/E 2.13; 1.06 to 3.80), and an excess from 0-7.5 km of cancer of the lung, stomach and pancreas combined, and prostate (O/Es ranged from 1.09 to 1.13). Only the findings from lung cancer were suggestive of a decline in risk with distance, especially in the later period (1982-9). There were 9196 cancer deaths (1981-92) from 0-7.5 km (O/E 1.04; 95% CI 1.02 to 1.06) and 308 from 0-1 km (O/E 1.24; 1.11 to 1.39); and 25507 non-cancer deaths (O/E 1.02; 1.01 to 1.04) from 0-7.5 km and 745 (O/E 1.14; 1.06 to 1.22) from 0-1 km. There was evidence of a decline in mortality with distance for all cancers combined, lung cancer (P = 0.001 for each), and colorectal cancer (P < 0.05), and also for non-cancers (P = 0.001). Proportional mortality analyses suggested a decline in risk with distance for lung cancer (P = 0.003) but not for all cancers or the site specific cancers examined. There was no evidence of an excess in the incidence or mortality from brain cancer. For cancer mortality in the inner-most wards, the findings were, for the most part, well within the range of variation across the region as a whole. CONCLUSIONS: The study provides limited and inconsistent evidence for a localised excess of cancer in the vicinity of the PBI plant. At present, further investigation does not seem warranted other than continued surveillance of mortality and cancer incidence in the locality.

Cancer incidence near radio and television transmitters in Great Britain. II. All high power transmitters.

A small area study of cancer incidence, 1974-1986, near 20 high power television (TV) and frequency modulation (FM) radio transmitters in Great Britain was carried out to place in context the findings of an earlier study around the Sutton Coldfield transmitter. The national database of postcoded cancer registrations was used with population and socioeconomic data from the 1981 census. Cancers examined were adult leukemias, skin melanoma, and bladder cancer, following the findings in the earlier study of significant declines in risk of these cancers with distance from the Sutton Coldfield transmitter. Childhood leukemia and brain cancer were also examined. Statistical analysis was performed for all transmitters combined, four overlapping groups of transmitters defined by their transmission characteristics, and for all transmitters separately. There were 3,305 adult leukemia cases from 0-10 km (observed/expected (O/E) ratio = 1.03, 95% confidence interval (CI) 1.00-1.07). A decline in risk of adult leukemia was found for all transmitters combined (p = 0.05), two of the transmitter groups, and three of the single transmitters; for all transmitters combined, observed excess risk was no more than 15% at any distance up to 10 km, and there was no observed excess within 2 km of transmitters (O/E ratio = 0.97, 95% CI 0.78-1.21). For childhood leukemia and brain cancer, and adult skin melanoma and bladder cancer, results were not indicative of a decline in risk with distance from transmitters. The magnitude and pattern of risk found in the Sutton Coldfield study did not appear to be replicated. The authors conclude that the results at most give no more than very weak support to the Sutton Coldfield findings.

Cancer incidence near radio and television transmitters in Great Britain. I. Sutton Coldfield transmitter.

A small area study of cancer incidence in 1974-1986 was carried out to investigate an unconfirmed report of a "cluster" of leukemias and lymphomas near the Sutton Coldfield television (TV) and frequency modulation (FM) radio transmitter in the West Midlands, England. The study used a national database of postcoded cancer registrations, and population and socioeconomic data from the 1981 census. Selected cancers were hematopoietic and lymphatic, brain, skin, eye, male breast, female breast, lung, colorectal, stomach, prostate, and bladder. Expected numbers of cancers in small areas were calculated by indirect standardization, with stratification for a small area socioeconomic index. The study area was defined as a 10 km radius circle around the transmitter, within which 10 bands of increasing distance from the transmitter were defined as a basis for testing for a decline in risk with distance, and an inner area was arbitrarily defined for descriptive purposes as a 2 km radius circle. The risk of adult leukemia within 2 km was 1.83 (95% confidence interval 1.22-2.74), and there was a significant decline in risk with distance from the transmitter (p = 0.001). These findings appeared to be consistent over the periods 1974-1980, 1981-1986, and were probably largely independent of the initially reported cluster, which appeared to concern mainly a later period. In the context of variability of leukemia risk across census wards in the West Midlands as a whole, the Sutton Coldfield findings were unusual. A significant decline in risk with distance was also found for skin cancer, possibly related to residual socioeconomic confounding, and for bladder cancer. Study of other radio and TV transmitters in Great Britain is required to put the present results in wider context. No causal implications can be made from a single cluster investigation of this kind.

Difficulties in predicting outcome in cardiac surgery patients.

OBJECTIVE: To evaluate a novel combination of preoperative, intraoperative, and postoperative variables (including the Parsonnet, and the Acute Physiology and Chronic Health Evaluation II and III [APACHE II and III] scores) in cardiac surgery patients in order to predict hospital outcome, complications, and length of stay. DESIGN: Prospective survey. SETTING: Adult intensive care unit (ICU) at a tertiary care cardiothoracic surgery center. PATIENTS: All cardiac surgery patients admitted to the ICU over a 1-yr period. INTERVENTIONS: Medical history, Parsonnet score, intraoperative data (including bypass and ischemic times), APACHE II and III scores, complications, and outcome were collected for each patient. MEASUREMENTS AND MAIN RESULTS: One thousand eight patients were entered into the study. The mean Parsonnet score was 7.8 (range 0 to 33), mean APACHE II score 11.8 (range 2 to 33), and mean APACHE III score 42.5 (range 9 to 132). ICU mortality rate was 2.7% and hospital mortality rate was 3.8%. The mean APACHE II predicted risk of dying was 5.31%, which gave a standardized mortality ratio of 0.71. The above scores were all statistically well correlated with hospital mortality. Further, a logistic regression model was developed for the probability of hospital death. This model (which included bypass time, need for inotropes, mean arterial pressure, urea, and Glasgow Coma Scale) had an area under the receiver operating characteristic curve of 0.87, while the Parsonnet score had an area of 0.82 and the APACHE II risk of dying had an area of 0.84. CONCLUSIONS: Cardiac surgery remains a difficult area for outcome prediction. A combination of intraoperative and postoperative variables can improve predictive ability.

Trends in childhood leukaemia in the Nordic countries in relation to fallout from atmospheric nuclear weapons testing.

OBJECTIVE: To obtain further information about the risks of childhood leukaemia after exposure to ionising radiation at low doses and low dose rates before or after birth or to the father's testes shortly before conception. DESIGN: Observational study of trends in incidence of childhood leukaemia in relation to estimated radiation exposures due to fallout from atmospheric nuclear weapons testing during the 1950s and 1960s. SETTING: Nordic countries. SUBJECTS: Children aged under 15 years. MAIN OUTCOME MEASURES: Incidence rates of leukaemia by age at diagnosis, sex, country, and calendar year of diagnosis or year of birth; exposure category; relation between leukaemia and exposure for children aged 0-14 and 0-4 separately. RESULTS: During the high fallout period the average estimated dose equivalent to the fetal red bone marrow was around 140 mu Sv and the average annual testicular dose 140 mu Sv. There was little evidence of increased incidence of leukaemia among children born in these years. Doses to the red bone marrow of a child after birth were higher, and during the high exposure period children would have been subjected to an additional dose equivalent of around 1500 mu Sv, similar to doses received by children in several parts of central and eastern Europe owing to the Chernobyl accident and about 50% greater than the annual dose equivalent to the red bone marrow of a child from natural radiation. leukaemia incidence and red marrow dose was not related overall, but rates of leukaemia in the high exposure period were slightly higher than in the surrounding medium exposure period (relative risk for ages 0-14: 1.07, 95% confidence interval 1.00 to 1.14; for ages 0-4: 1.11, 1.00 to 1.24). CONCLUSIONS: Current predicted risks of childhood leukaemia after exposure to radiation are not greatly underestimated for low dose rate exposures.

Mortality among United Kingdom servicemen who served abroad in the 1950s and 1960s.

The Registrar General's decennial supplements on occupational mortality provide only limited information on mortality in the armed forces in the United Kingdom. Mortality has therefore been studied among a group of 30,619 United Kingdom servicemen who served abroad in tropical or desert areas in the 1950s and 1960s, and who remained in the services for a total of at least five years. Mortality from all causes of death, all neoplasms, and all other known non-violent causes was lower than that expected from rates for all men in England and Wales, whereas mortality from accidents and violence was raised. These differences remained after adjustment for social class, affected both officers and other ranks, and had not disappeared even after the men had been followed up for at least 20 years. When mortality from 20 specific cancers and 10 other disease groups was examined there were significant excesses for cancers of the oesophagus (standardised mortality ratio (SMR) = 146; p = 0.03) and prostate (SMR = 156; p = 0.03), and significant deficits for cancers of the lung (SMR = 73; p less than 0.001), stomach (SMR = 66; p = 0.002), bladder (SMR = 53; p = 0.02), other specified neoplasms (SMR = 48; p = 0.001), coronary heart disease (SMR = 76; p less than 0.001), bronchitis, emphysema, and chronic obstructive lung disease (SMR = 42; p less than 0.001), and for five further groups of diseases unrelated to smoking or alcohol. Examination of mortality in each of the three services separately identified two specific hazards in the Royal Navy; seven deaths from mesothelioma occurred compared with less than 2.06 expected (p less than 0.005), and there was also an excess of neoplasms and of other diseases associated with alcohol (SMRs of 181 and 229; p = 0.002 and less than 0.001). Mortality from smoking related diseases other than those associated with alcohol was low in all three services, particularly among officers.