Lower-than-expected mortality

An update of a previous study (Axelson et al. 1978), Axelson (1986) evaluated an expanded cohort of 1,424 men (levels of trichloroethylene exposure inferred from measured urinary metabolite concentrations) and found a significant increase in incidences of bladder cancer and lymphomas, and a lower than expected incidence of total cancer mortality. A further update of this work (Axelson et al. 1994) expanded the cohort to include 249 women, tracking cancer morbidity over 30 years, and found no correlation between exposure concentration or exposure time and cancer incidence at any site. The highest standardized incidence ratio noted in this study was 1.56 (95% Cl of 0.51-3.64) for 5 cases of non-Hodgkin s lymphoma observed in men. Although four of these cases occurred in persons exposed for at least 2 years, and 3 cases had a latency of 10 years or more, urinary levels of TCA showed that 4 of the 5 cases were exposed to the lowest levels of trichloroethylene (urinary levels of TCA 0-49 mg/L). The study authors mentioned that a urinary TCA level below 50 mg/L corresponds to a trichloroethylene exposure concentration of about 20 ppm. The study authors concluded that "this study provides no evidence that trichloroethylene is a human carcinogen, i.e., when the exposure is as low as for this study population."... 

Cause-specific mortality was lower than expected for all causes of death at a weapons facility where isobutyl acetate was one of several commonly used solvents. ... 

The Chi-Chi earthquake struck Taiwan on October 9, 1999, killing 2,347 people and injuring 8,722 (Liang et al., 2001). Children 0-9 years had among the lowest mortality rates (12.65/100,000 Liang et al., 2001). This mortality rate was lower than expected, possibly... 

Interpretation of cohort studies is not always straightforward there are a number of selection effects and biases that must be considered. Cohort studies routinely report that the mortality of active workers is less than that of the population as a whole. It is not an unexpected finding since workers usually have to undergo some sort of selection process to become or remain workers. Nevertheless, this selection effect, known as the healthy worker effect, can lead to considerable arguments over the interpretation of study results, particularly if the cancer mortality is as expected but the all-cause mortality is much lower than expected. However, even an experimental science such as toxicology is not without a similar problem of interpretation, namely, the problem of distinguishing between the effects of age and treatment on tumor incidence. 

The studies at the Rocky Flats facility consisted of mortality studies of workers at the plant (Voelz et al 1983b Wilkinson et al. 1987) and a study of residents living downwind from the facility (Johnson 1981, 1988). Voelz etal. (1983b) reported the results of a study of 7,112 workers employed at the Rocky Flats facility during 1952-1979. Observed deaths were significantly lower than expected (452 vs. 831). Malignant neoplasms were also lower than expected (107 vs. 167). 

Table 4-7 shows observed deaths in the three categories compared with age-specific expected numbers based on mortality data on U.S. white males born in 1891. In general, the observed expected ratios are lower than 1, apparently because the preinduction medical examinations excluded men not in good health. Deaths did increase sharply in the mustard-gas roster for 1930-1939. 

Smith et al. [106] investigated embryonic mortality of coho and chinook salmon from the Credit River, Lake Ontario, 1990, correlated to H4IIE-derived TEQs. No correlation was found, but TEQs were correlated with concentrations of PCBs and other chlorocarbons, as expected. The authors pointed out that the relative sensitivity of coho salmon to dioxin-like embryotoxic-ity is much lower than in lake trout, and that H4IIE is not a good measure... 

Standardized mortality ratio (SMR) in the subgroup was 328 (5 observed/1.52 expected deaths, 95% confidence interval [Cl] 33-61, p value not reported). Kimbrough et al. (1999a) found no significant increases in mortality related to ischemic heart disease, hypertension with heart disease, other diseases of the heart, cerebrovascular disease, or circulatory system (arteries, veins, pulmonary circulation) in a study of 7,075 male and female capacitor workers. One of the subgroups (male salaried workers) in this study had a significantly decreased risk of mortality from ischemic heart as indicated by an SMR lower than 100 (44 observed/97.5 expected deaths, SMR=45, 95% Cl 107-766, p<0.01). Neither of these studies reported adequate quantitative exposure data. The inconsistent results of these studies could be due to differences in exposure levels, durations, and latencies, as well as types of Aroclors and cohort sizes. Additional information on these studies is provided in Section 3.2.8.2.I. 

The high morbidity and mortality in patients with ruptured aneurysms prompted interest in repair of aneurysms that are diagnosed before they have ruptured. Following publication of the initial results of the International Study of Unruptured Intracranial Aneurysms (ISUIA 1998), enthusiasm for this strategy was markedly reduced. In this study patients were classified in those with no history and those with history of SAH. The risk posed by unruptured aneurysms was reported lower than had been previously expected and also morbidity and mortality to treat aneurysms were higher than had previously been reported. The updated results of the same group analysed 6544 patients years of prospective follow up of untreated aneurysms, 1692 had no treatment, 1917 had surgical repair and 451 had their unruptured aneurysm coiled. The cut off... 

Another observational study, the first National Health and Nutrition Examination Survey, examined vitamin C intake using both food frequency and 24-hr recall questionnaires (Enstrom et ai, 1992). The 11,349 men and women in the study, ages 25-74, were followed for a median period of ten years. CVD mortality rates were 34% lower (relative risk = 0.66 95% Cl = 0.53-0.82) than expected among participants with the highest vitamin C intake defined as 50 mg or more from the diet plus regular supplements (Table IV). One potential limitation of this study was the inability to examine and control for the possible correlation of vitamin C with other vitamin supplements, particularly vitamin E. 

Most patients with established hypertension do not make sufficient lifestyle changes, do not take medication or do not take enough medication to achieve control. Even if adequately treated, patients may not lower their risk to that of persons with normal BP. It has to be emphasized that BP rise and high BP are not inevitable consequences of aging. Therefore an effective population-wide strategy to prevent BP rise with age could affect overall cardiovascular morbidity and mortality as much or more than that of treating only those with established hypertension. A population-wide approach has been shown to prevent or delay the expected rise in BP in susceptible... 

These cannot be accurately defined. But both patients and nonpatients justifiably expect some guidance, and doctors and government departments will wish to be helpful. They may reasonably advise as a safe or prudent maximum (there being no particular individual contraindication) men, not more than 21 units per week (and not more than 4 units in any one day), and women, 14 units per week (and not more than 3 units in any one day). Consistent drinking more than these amounts carries a progressive risk to health (see also Alcoholic drinks and mortality, below). In other societies recoirunended maxima are higher or lower. 

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