Associations between daily cause-specific mortality and concentrations of ground-level ozone in Montreal, Quebec.

The authors investigated the association between daily variations in ozone and cause-specific mortality. Fixed-site air pollution monitors in Montreal, Quebec, provided daily mean levels of ozone, particles, and other gaseous pollutants. Information on the date and underlying cause of death was obtained for residents of Montreal who died in the city between 1984 and 1993. The authors regressed the logarithm of daily counts of cause-specific mortality on mean levels of ozone, after accounting for seasonal and subseasonal fluctuations in the mortality time series, non-Poisson dispersion, and weather variables. The effect of ozone on mortality was generally higher in the warm season and among persons aged 65 years or over. For an increase in the 3-day running mean concentration of ozone of 21.3 microg/m(3), the percentage of increase in daily deaths in the warm season was the following: nonaccidental deaths, 3.3% (95% confidence interval (CI): 1.7, 5.0); cancer, 3.9% (95% CI: 1.0, 6.91); cardiovascular diseases, 2.5% (95% CI: 0.2, 5.0); and respiratory diseases, 6.6% (95% CI: 1.8, 11.8). These results were independent of the effects of other pollutants and were consistent with a log-linear response function.

Identification of persons with cardiorespiratory conditions who are at risk of dying from the acute effects of ambient air particles.

This study was undertaken to identify subgroups of the population susceptible to the effects of ambient air particles. Fixed-site air pollution monitors in Montreal, Quebec, Canada, provided daily mean levels of various measures of particulates and gaseous pollutants. Total sulfates were also measured daily (1986-1993) at a monitoring station 150 km southeast of the city (Sutton, Quebec, Canada). We used coefficient of haze (COH), extinction coefficient, and Sutton sulfates to predict fine particles and sulfates from a fine particles model for days that were missing. We used the universal Quebec medicare system to obtain billings and prescriptions for each Montreal resident who died in the city from 1984 to 1993. These data were then used to define cardiovascular and respiratory conditions that subjects had before death. Using standard Poisson regression time-series analyses, we estimated the association between daily nonaccidental mortality and daily concentrations of particles in the ambient air among persons with cardiovascular and respiratory conditions diagnosed before death. We found no persuasive evidence that daily mortality increased when ambient air particles were elevated for subgroups of persons with chronic upper respiratory diseases, airways disease, cerebrovascular diseases, acute coronary artery disease, and hypertension. However, we found that daily mortality increased linearly as concentrations of particles increased for persons who had acute lower respiratory diseases, chronic coronary artery diseases (especially in the elderly), and congestive heart failure. For this latter set of conditions, the mean percent increase in daily mortality (MPC) for an increase in the COH across its interquartile range (18.5 COH units per 327.8 linear meters), averaged over the day of death and the 2 preceding days, was MPC = 5.09% [95% confidence interval (CI) 2.47-7.79%], MPC = 2.62 (95% CI 0.53-4.75%), and MPC = 4.99 (95% CI 2.44-7.60%), respectively. Adjustments for gaseous pollutants generally attenuated these associations, although the general pattern of increased daily mortality remained. In addition, there appeared to be a stronger association in the summer season. The positive associations found for persons who had acute lower respiratory diseases and congestive heart failure are consistent with some prevailing hypotheses and may also be consistent with recent toxicologic data implicating endothelins. Further epidemiologic studies are required to confirm these findings.

The association between daily mortality and ambient air particle pollution in Montreal, Quebec. 1. Nonaccidental mortality.

This study was undertaken to determine whether variations in concentrations of particles in the ambient air of Montreal, Quebec, during the period 1984 to 1993, were associated with daily variations in nonaccidental mortality. Fixed-site air pollution monitors in Montreal provided daily mean levels of various measures of particulates and gaseous pollutants. Total sulfates were also measured daily (1986-1993) at a monitoring station 150 km southeast of the city (Sutton, Quebec). We estimated associations for PM(2.5), PM(10), total suspended particles, coefficient of haze (COH), extinction coefficient, and sulfates. We used coefficient of haze, extinction coefficient, and Sutton sulfates to predict fine particles and sulfates for days that were missing. To estimate the associations between nonaccidental mortality and ambient air particles, we regressed the logarithm of daily counts of nonaccidental mortality on the daily mean levels for the above measures of particulates, after accounting for seasonal and subseasonal fluctuations in the mortality time series, non-Poisson dispersion, weather variables, and gaseous pollutants. There were 140,939 residents of Montreal who died during the study period. We found evidence of associations between daily nonaccidental deaths and most measures of particulate air pollution. For example, the mean percentage increase (MPC) for an increase of total suspended particles of 28.57 microg/m(3) (interquartile range, IQ), evaluated at lag 0 days, was 1.86% (95% confidence interval (CI): 0.00-3.76%), and for an increase of coefficient of haze (IQ=18.5 COH units per 327.8 linear m) the MPC was 1.44% (95% CI: 0.75-2.14%). These results are similar to findings from other studies (the mean percentage increase in nonaccidental deaths for a 100 microg/m(3) increase in daily total suspended particles was 6.7%). We also found increases for fine particles and for inhalable particles, but the confidence intervals included unity. All measures of sulfates showed increased daily mortality; e.g., the MPC for sulfates from fine particles (IQ=3.51 microg/m(3)) was 1.86% (95% CI: 0.40-3.35%). We generally found higher excesses in daily mortality for persons 65 years of age and for exposures averaged across lags 0, 1, and 2 days. The slope of the association between daily mortality and ambient air particles in Montreal, which has lower levels of pollution than most major urban centers, is similar to that reported in most other industrialized cities. This study therefore provides further evidence that the association is linear and that any threshold effect, should it exist, would be found at lower levels of air pollution than those found in Montreal.

The association between daily mortality and ambient air particle pollution in Montreal, Quebec. 2. Cause-specific mortality.

This study was undertaken to determine whether variations in concentrations of particulates in the ambient air of Montreal, Quebec, during the period 1984 to 1993, were associated with daily variations in cause-specific daily mortality. Fixed-site air pollution monitors in Montreal provided daily mean levels of various measures of particles and gaseous pollutants. Total sulfate was also measured daily (1986-1993) at a monitoring station 150 km southeast of the city (Sutton, Quebec). We used coefficient of haze (COH), extinction coefficient, and sulfate from the Sutton station to predict fine particles and sulfate from fine particles for days that were missing. We estimated associations between cause-specific mortality and PM(2.5), PM(10), predicted fine particles and fine sulfate particles, total suspended particles, coefficient of haze, extinction coefficient, and total sulfate measured at the Sutton station. We selected a set of underlying causes of death, as recorded on the death certificates, as the endpoint and then regressed the logarithm of daily counts of cause-specific mortality on the daily mean levels for the above measures of particulates, after accounting for seasonal and subseasonal fluctuations in the mortality time series, non-Poisson dispersion, weather variables, and gaseous pollutants. We found positive and statistically significant associations between the daily measures of ambient particle mass and sulfate mass and the deaths from respiratory diseases and diabetes. The mean percentage change in daily mortality (MPC), evaluated at the interquartile range for pollutants averaged over the day of death and the preceding 2 days, for deaths from respiratory diseases was MPC(COH)=6.90% (95% CI: 3.69-10.21%), MPC(Predicted PM2.5)= 9.03% (95% CI: 5.83- 12.33%), and MPC(Sutton sulfate)=4.64% (95% CI: 2.46-6.86%). For diabetes, the corresponding estimates were MPC(COH)=7.50% (95% CI: 1.96-13.34%), MPC(Predicted PM2.5)=7.59% (95% CI: 2.36-13.09%), and MPC(Sutton sulfate)=4.48% (95% CI: 1.08-7.99%). Among individuals older than 65 years at time of death, we found consistent associations across our metrics of particles for neoplasms and coronary artery diseases. Associations with sulfate mass were also found among elderly persons who died of cardiovascular diseases and of lung cancer. These associations were consistent with linear relationships. The associations found for respiratory diseases and for cardiovascular diseases, especially in the elderly, are in line with some of the current hypotheses regarding mechanisms by which ambient particles may increase daily mortality. The positive associations found for cancer and for diabetes may be understood through a general hypothesis proposed by Frank and Tankersley, who suggested that persons in failing health may be at higher risk for external insults through the failure of regulating physiological set points. The association with diabetes may be interpreted in light of recent toxicological findings that inhalation of urban particles in animals increases blood pressure and plasmatic levels of endothelins that enhance vasoconstriction and alter electrophysiology. Further research to confirm these findings and to determine whether they are causal is warranted.

Identifying subgroups of the general population that may be susceptible to short-term increases in particulate air pollution: a time-series study in Montreal, Quebec.

This study was undertaken in order to shed light on which groups of the general population may be susceptible to the effects of ambient particles. The objectives of the study were (1) to determine whether concentrations of particles in the ambient air of Montreal, Quebec, were associated with daily all-cause and cause-specific mortality in the period 1984 to 1993, and (2) to determine whether groups of the population had higher than average risks of death from exposure to particles. From the network of fixed-site air pollution monitors in Montreal we obtained daily mean levels of various measures of particles, gaseous pollutants, and weather variables measured at Dorval International Airport. We also used measurements of sulfate from an acid rain monitoring station 150 km southeast of the city (Sutton, Quebec). We estimated associations for particulate matter (PM) with an aerodynamic diameter of 10 microns or smaller (PM10), or 2.5 microns or smaller (PM2.5), total suspended particles (TSP), coefficient of haze (COH), an extinction coefficient, and sulfate. Because substantial data for fine particles were missing, we developed a regression model to predict PM2.5 and to predict sulfate from PM2.5. In the main body of the report, we present results for COH, predicted PM2.5, and sulfate. Detailed results for all pollutants are included in Appendices H through O, which are available on request from Health Effects Institute and from the HEI web site at www.healtheffects.org. To address the first objective, we made use of the underlying causes of death among all 140,939 residents of Montreal who died between 1984 and 1993. We regressed the logarithm of daily counts of cause-specific mortality on the daily mean levels for a variety of measures of particles, accounting for seasonal and subseasonal fluctuations in the mortality time series, overdispersion, and weather factors. To address the second objective, we developed algorithms to define conditions that subjects had prior to death, with the focus on cardiopulmonary diseases. These algorithms were based on information retained on the databases of the universal Quebec Health Insurance Plan (QHIP). The databases include records of all procedures (e.g., type of surgery), physician visits, and consultations carried out by all physicians in Quebec. For persons > or = 65 years and for all recipients of social assistance the prescription database contains records of all pharmaceuticals dispensed (type of medication, dose, quantity). For each group of conditions defined, we used the same statistical model that was used in the analyses of all nonaccidental causes of death. In the analyses of cause-specific mortality, we found evidence of associations for all nonaccidental causes of death and specific causes of death--cancer, coronary artery disease, respiratory diseases, and diabetes--that were consistent across most metrics of ambient air particle concentrations, evaluated as the 3-day mean of particle concentrations measured on the day of death (lag 0) and on each of the two days before death (lag 1, lag 2). Associations for all cardiovascular diseases combined were found only with sulfate. As well, we generally found increased daily mortality for persons 65 years of age and over. The results for all nonaccidental causes of death are similar to findings from other studies; the mean percent increase in mortality for a 100 micrograms/m3 increase in daily TSP at lag 0 was 6.7%. In the analyses of the groups defined from the QHIP data, there was little evidence of associations with air pollutants among persons who before death were classified as having acute or chronic upper respiratory diseases, airways diseases, hypertension, acute coronary artery diseases, and cerebrovascular diseases. On the other hand, we found consistent increases across most types of ambient particles for persons who had cancer, acute lower respiratory diseases, any form of cardiovascular disease, chronic coronary artery diseases, and congestive heart failure. As well, we found an association for individuals who did not have any cardiovascular disease, lower respiratory diseases, and cancer. This latter group consisted of persons who had no interactions with the health care system one year before death (12%) and individuals with a wide variety of potentially fatal diseases (52%), including neurological conditions (12%), diabetes (8%), cardiac dysrhythmias (8%), dementia (6%), organic psychotic disorders (6%), and anemias (4%). As statistical power was reduced in the analyses presented above, differences between groups (e.g., < 65 and > or = 65 year age groups) were not usually statistically significant. The association with diabetes has not been reported previously, and this needs to be replicated in other studies. (ABSTRACT TRUNCATED)

Risk assessment--the mother of all uncertainties. Disciplinary perspectives on uncertainty in risk assessment.

Uncertainty in the detection and evaluation of chemical hazards to health leads to challenges when conducting risk assessments. Some of the uncertainty has to do with data, some with incomplete understanding of processes, and some with the most fundamental ways of viewing the questions. True variability--across space, in time, or among individuals--complicates the search for understanding many important aspects of risk. A few statistical and toxicologic tools are available to assess uncertainty. Three methods of classifying uncertainty are briefly discussed. In addition, our disciplinary background may influence how we view and discuss variability and uncertainty. We rarely know as much as we think we do (and not just in risk assessment). Great uncertainty is likely to remain an important part of risk assessment for some decades to come.

Randomised trial of albendazole and pyrantel in symptomless trichuriasis in children.

BACKGROUND: We aimed to find out whether symptomless infection with Trichuris trichiura is associated with impairment of growth and to assess the effect of a multiple-doses regimen of anthelmintic drugs on the growth of children. METHODS: In a community based trial, 622 Mexican children were randomly allocated one of three treatment regimens: 3 days of albendazole 400 mg daily (high efficacy); one dose of albendazole 400 mg (moderate efficacy); one dose of pyrantel (pyrantel embonate) 11 mg/kg (low efficacy). Growth was monitored for 12 months. Analyses were by intention to treat. FINDINGS: 113 (18%) children were lost to follow-up--34 from the pyrantel group, 45 from the albendazole 400 mg group, and 34 from the albendazole 1200 mg group. Among the 127 children with heavy pretreatment infections, albendazole 1200 mg was better than pyrantel in terms of an increase in arm circumference (mean 0.26 cm, p=0.044). Among the 381 children with low pretreatment levels of infection, changes in weight (mean difference between groups -0.33 kg, p=0.036), arm circumference (-0.18 cm, p=0.0095), and thickness of triceps skinfold (-0.41 mm, p=0.0031) were less in children on albendazole 1200 mg than in those on pyrantel. INTERPRETATION: Symptomless trichuriasis impairs growth and albendazole or pyrantel may affect growth, independently of a therapeutic action on parasites. Possible toxic effects of high-dose albendazole require further investigation.

Trends in cancer mortality: perspectives from Italy and the United States.

Cancer continues to be a major public health problem in Italy, as it is throughout the world. We analyzed age-adjusted mortality rates for all cancers combined and for specific cancer sites in Italy for five year periods from 1950 to 1989. We compared trends in Italian cancer mortality to those observed in the United States during the same time period. We also considered some ancillary data including age-specific mortality rates, as well as incidence and five year relative survival data from the Modena Province. Age-adjusted cancer mortality rates in Italy are increasing in males and, to a lesser extent, females. This finding is in contrast to a recent plateau in age-adjusted cancer mortality rates in the United States. In Italy, stomach cancer mortality has declined substantially, counteracting marked increases in lung cancer mortality, particularly in males, and breast and lung cancer in females. Changes in cancer mortality in Italy, as in the US, have been driven primarily by changes in disease incidence rather than advances in therapeutics. These data suggest a need for realignment of cancer control resources toward prevention, particularly with regard to lung cancer and tobacco usage.

Cancer undefeated.

BACKGROUND: Despite decades of basic and clinical research and trials of promising new therapies, cancer remains a major cause of morbidity and mortality. We assessed overall progress against cancer in the United States from 1970 through 1994 by analyzing changes in age-adjusted mortality rates. METHODS: We obtained from the National Center for Health Statistics data on all deaths from cancer and from cancer at specific sites, as well as on deaths due to cancer according to age, race, and sex, for the years 1970 through 1994. We computed age-specific mortality rates and adjusted them to the age distribution of the U.S. population in 1990. RESULTS: Age-adjusted mortality due to cancer in 1994 (200.9 per 100,000 population) was 6.0 percent higher than the rate in 1970 (189.6 per 100,000). After decades of steady increases, the age-adjusted mortality due to all malignant neoplasms plateaued, then decreased by 1.0 percent from 1991 to 1994. The decline in mortality due to cancer was greatest among black males and among persons under 55 years of age. Mortality among white males 55 or older has also declined recently. These trends reflect a combination of changes in death rates from specific types of cancer, with important declines due to reduced cigarette smoking and improved screening and a mixture of increases and decreases in the incidence of types of cancer not closely related to tobacco use. CONCLUSIONS: The war against cancer is far from over. Observed changes in mortality due to cancer primarily reflect changing incidence or early detection. The effect of new treatments for cancer on mortality has been largely disappointing. The most promising approach to the control of cancer is a national commitment to prevention, with a concomitant rebalancing of the focus and funding of research.

Randomization in the Canadian National Breast Screening Study: a review for evidence of subversion.

The authors assess the randomization strategy that had been used in the Canadian National Breast Screening Study (NBSS). Document experts at a private investigation and security company were hired to assist in reviewing instances in which names of subjects were altered in the "allocation books" (the basic instrument used to assign, at random, participants to either the mammography or the usual-care arm). The review was restricted to records from 3 NBSS centres where women assigned to the mammography arm had a distinctly higher (not necessarily significant) number of deaths from breast cancer than those assigned to the usual-care arm, and to records from 2 centres where, for limited periods, administrative problems were reported. In most cases the underlying, original name could be identified. The document experts found no evidence of a deliberate attempt to conceal the alterations. A search of the NBSS database for the underlying and superimposed names revealed that only 1 of the women whose name had been deleted or superimpsed died of breast cancer. She was in the mammography arm. The authors' thorough review of ways in which the randomization could have been subverted failed to uncover credible evidence of it. They conclude that even if there had been acts of subversion, they could only have been few in number and, given that there was only 1 death from breast cancer in the group reviewed, the alterations could have had only a trivial effect on the study findings as reported in 1992.