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Anatomy of the health worker effect - a critique of summary statistics employed in occupational epidemiology.

The "healthy worker effect," perhaps more accurately termed the "active worker effect" has been acknowledged by numerous investigators who have disregarded its significance. The healthy worker effect is expressed by SMRs (standardized mortality ratios) and influenced by the following three factors: (i) selection bias, (ii) improved socioeconomic status, and (iii) the conventional way of calculating SMRs. An examination of these three factors shows that selection for "employability" is probably the most significant factor for the healthy worker effect. For example, the shorter the observation, the smaller the SMR, and the stronger the health worker effect. Secondly, improved socioeconomic status as a result of employment has been shown to lower mortality. Last, although the SMR has the advantage of estimating relative risk in a small sample, it suffers many methodological pitfalls. It is recommended that at least three parameters be used to summarize mortality experience among the employed: (i) relative risk, (ii) attributable risk, and (iii) life expectancy.

Employment↗

Characteristics of the healthy survivor effect among male and female Hanford workers.

BACKGROUND: The healthy survivor effect is a selection process whereby healthy workers are selectively retained in the work force while unhealthy workers are removed. Understanding this phenomenon is integral to the accurate assessment of exposure effects in occupational cohorts. To date, scarce information has been published on the descriptive characteristics of the healthy survivor effect. METHODS: Follow-up mortality data on 44,154 employees from the Hanford nuclear facility for the period of 1944-1986 were used to estimate the healthy survivor effect according to frequently measured sociodemographic characteristics. RESULTS: While Hanford employees did not exhibit a stepwise decline in standardized mortality ratios according to duration of employment, workers in the longest employment duration category demonstrated a substantial survival advantage compared to the rest of the cohort. This effect was present in both males and females, and in all but the following subgroups: males hired at or after age 40, females hired before age 40, and females classified as both professional and nonprofessional. CONCLUSION: The findings of the present study suggest that investigators should consider the potential confounding role of the healthy survivor effect when relying on SMRs, or other methods, to assess the adverse health effects of exposure in occupational cohorts. Further studies should be conducted, however, to assess variation in the healthy survivor effect according to sociodemographic characteristics.

Adult↗

Comparison of standardized mortality ratios (SMRs) obtained from use of reference populations based on a company-wide registry cohort to SMRs calculated against local and national rates.

The DuPont Company has maintained a mortality registry for all active and pensioned U.S. employees since 1957. Standardized mortality ratios (SMRs) for each plant site in the U.S. can be calculated based on the comparison with the entire U.S. DuPont population or with a regional subset of DuPont employees. We compared the SMRs derived from a large, international cohort mortality study of chloroprene workers (IISRP study) with those derived from the entire DuPont Registry and appropriate subpopulations of the registry for two U.S. neoprene plants--Louisville (Kentucky) and Pontchartrain (Louisiana). SMRs from the IISRP study for the Louisville cohort based on national rates for all causes of death, all cancers, respiratory cancer, and liver cancer are higher than those based on local mortality rates. Both the national and local comparisons (several counties surrounding each plant) for all-cancer SMRs are lower than 1.0, the local comparison being statistically significantly reduced. In contrast, the SMRs based on the total U.S. DuPont worker mortality rates for all causes of death (1.13), all cancers (1.11), and respiratory cancers (1.37) are statistically significantly increased. The SMR for liver cancer (1.27), although elevated, is not statistically significant. SMRs based on DuPont Region 1 were closer to 1.0, and the SMR for all cancers was no longer significant. Stratification of the Louisville subcohort of males using the same cumulative exposure categories used in the IISRP study yielded SMRs calculated against DuPont Region 1 that were generally higher than those calculated against U.S. and local rates. Only the third exposure category showed SMRs statistically significantly above 1.0 for all cancers and for cancer of bronchus, trachea, and lung. However, there does not appear to be an exposure-response trend. The SMRs from the IISRP study for the Pontchartrain cohort based on national rates are higher than those based on local rates for all causes of death, but all are less than 1.0. The all-cause SMRs for both local and national comparisons are significantly reduced. There were no deaths from liver cancers observed in this cohort. Comparisons of the Pontchartrain cohort against the total U.S. DuPont worker mortality rates resulted in higher SMRs for all causes of death (0.98), all cancers (1.03), and respiratory cancer (1.08), but none were statistically significant. SMRs based on DuPont Region 2 showed very little change from those based on the total registry. The use of reference rates based on regional workers in the same large company produces SMRs lower than those based on the entire company population (regional socio-cultural effects) but higher than those based on geographically closer local general populations (healthy worker effect). The healthy worker effect is seen in cancer mortality rates as well as in other chronic diseases.

Chloroprene↗

Demonstration of the healthy worker survivor effect in a cohort of workers in the construction industry.

OBJECTIVES: To assess the potential of a healthy worker survivor effect due to differential occupational mobility in a cohort of construction workers. METHODS: A cohort of 10 809 male employees in the German construction industry aged 15-64 years was followed up for occupational mobility, early retirement due to permanent disability, and total mortality from 1986 to 1994. Using the Cox's proportional hazards model of relative rates (RRs) with 95% confidence intervals (95% CIs) of occupational mobility, early retirement and total mortality were estimated according to medical diagnoses at baseline after adjustment for various covariates. RESULTS: During follow up, 2472 subjects changed employment, 359 employees were granted a disability pension for health reasons and 188 subjects died. A wide range of chronic diseases was associated with increased rates of early retirement and total mortality but not occupational mobility. However, a healthy worker survivor effect was identified related to disorders of the back and spine (ninth revision of the international classification of diseases, ICD-9, code 720-4), a common predictor of both occupational mobility (RR 1.17, 95% CI 1.04 to 1.32) and early retirement (RR 1.50, 95% CI 1.20 to 1.88). In total, there were about as many events of occupational changes (n = 41) as events of early retirement due to permanent disability (n = 39) significantly attributable to disorders of the back and spine. Differential occupational mobility preceded differential early retirement due to permanent disability by more than one decade. CONCLUSIONS: These findings show the need to consider a healthy worker survivor effect due to occupational mobility in occupational epidemiological research. Furthermore these results underline the necessity of further health promotion targeting work related conditions in the construction industry.

Adolescent↗

The healthy worker survivor effect and mortality at two automotive engine manufacturing plants.

Attributes such as time since hire or length of followup may be important in occupational mortality due to the "healthy worker survivor effect." In a regression analysis of mortality odds ratios at two automotive engine plants, strong effects of overall employment duration (latency weighted) were observed in addition to effects for (similarly weighted) cumulative exposures. The duration effects were negative for several cancer and noncancer outcomes, and confounded exposure effects. The lung cancer odds ratio declined to 0.68 (95% CI = 0.51, 0.90) at the mean duration of employment. With control for employment duration, adjusted lung cancer odds ratios for work as millwrights increased from 3.0 to 3.8, and for work in cylinder head production, from 3.3 to 3.9. Several causes of death with strong duration effects were smoking-related, suggesting diminished smoking risk factors with increasing employment duration. Similarly, trends for cirrhosis of the liver mortality suggested the alcohol risk factor is smaller in long-duration workers. If personal risk factors are an important component of the healthy worker survivor effect, they could be powerful negative confounders of exposure-response for related outcomes. Including a term for employment duration in regression models appears to partially correct for healthy worker survivor bias.

Aged↗

The sick person effect.

Very often criteria by which subjects are selected for epidemiological studies are associated in some manner with their health. The Healthy Worker Effect (HWE) or Healthy Person Effect (HPE) is well known. Little has been said about the converse case in which selection is associated with decreased health status, the Sick Person Effect (SPE). The SPE may introduce a bias for some cohort, most clinical follow-up, and some case-control studies when risks are standardized against an inappropriate referent. We demonstrate the existence of the SPE in two studies. Study 1 compares the incidence of a number of different diseases among individuals who were selected as children for medical treatment with that among their siblings. Study 2 computes the Standardized Morbidity Ratios (SmRs) for various acute and chronic diseases for individuals who have reported particular chronic symptoms. The SPE is clearly apparent for all instances where the general population is taken as the referent. The HPE and SPE may present serious problems for the validity of conclusions with respect to risk levels.

Bias↗

Time-related aspects of the healthy worker survivor effect.

PURPOSE: Health is important for continued employment and therefore continued accrual of occupational exposure; furthermore, steady employment can benefit health. Consequently, bias can occur in estimates of cumulative exposure-mortality associations. This has been called the healthy worker survivor effect (HWSE). The processes associated with the HWSE tend to lead to variation in mortality rates with time-since-termination of employment, most notably a peak in mortality shortly after termination of employment. We use simulations and an empirical example to demonstrate that time-since-termination can be a confounding factor in analyses of occupational-exposure-mortality associations. METHODS: Simulation data were generated for 20,000 workers followed for 40 years under a model of no effect of employment duration (a proxy for cumulative exposure) on mortality. Proportional hazards regression methods were used to quantify exposure-mortality associations and evaluate methods to control for the HWSE. Results were derived after 100 iterations of the simulation. Relationships between employment duration and mortality were also investigated in a cohort of 122,247 male utility workers with adjustments for time since termination. RESULTS: Simulation data show a peak in mortality rates in the first year after termination of employment which declined in magnitude with continued time since termination of employment; average employment duration also declined with time since termination of employment. This led to confounding of cumulative-exposure-mortality associations, with spurious evidence of a positive association between cumulative exposure and mortality in the post-termination period. Adjustment for time-since-termination eliminated this spurious association; in contrast, adjustment for a binary indicator of employment status led to positively-biased relative rate estimates. A similar pattern was observed in analyses of utility worker data. The log relative rate of all cancer mortality is -0.12+/-0.03 per decade of employment without adjustment for time-since-termination, and -0.01+/-0.03 with adjustment for time-since-termination of employment. CONCLUSIONS: The HWSE can lead to temporal variation in mortality rates that is correlated with cumulative exposure. Under these conditions, adjusting for time-since-termination of employment may reduce bias in estimates of cumulative-exposure-mortality trends more effectively than the commonly-used method of adjusting for a binary indicator of employment status.

Adolescent↗

Occupational mortality studies. Principles of validity.

Two common practices of occupational mortality studies have no model in experimentation: (a) the use of the "general population" as a reference population and (b) the use of the total number of deaths as a surrogate for the population-time of follow-up. The former tends not to secure validity in terms of (i) comparability of effects, ie, identity of the extraneous effects of the compared experiences; (ii) comparability of populations, ie, absence of intractable confounding; and (iii) comparability of information, ie, identity of the certification of deaths from the illness of interest for the contrasted populations. The use of a carefully selected, occupational reference population is necessary for all three types of comparability. When deaths from other (auxiliary) diseases are used to estimate the relative magnitudes of the compared populations, careful selectivity is again called for. With respect to auxiliary causes of death, also, the compared occupational populations must satisfy all three aspects of comparability, with the added requirement that the exposure under study have no effect. The "healthy worker effect" is the result of failure to use comparable reference populations in occupational mortality studies.

Epidemiologic Methods↗

Symptom reports and mortality in an occupational cohort.

The relationship between baseline symptom reports and subsequent mortality over a 24-year period was examined in a group of 1,224 white male nonsupervisory paper workers. Symptom reports were measured via the Cornell Medical Index, and the vital status of each participant was ascertained by reviewing company personnel records and death certificates. Analyses based on proportional hazards models suggest that symptom reports are predictive of mortality (RR = 1.24; P = .0002), independent of the participant's age and biologic risk status at intake. Analyses based upon age-specific and age-standardized mortality ratios confirm that the paper workers were subject to a "healthy worker effect" (standardized mortality ratio [SMR] = 0.66), and that the healthy worker effect is attenuated (SMR = 0.77) among those participants reporting ten or more symptoms at the beginning of the follow-up period.

Adult↗

Adjusting for the healthy worker selection effect in cross-sectional studies.

BACKGROUND: In a cross-sectional study of musculoskeletal disorders, women employed in highly repetitive manual work (garment assembly) were found to have approximately double the risk observed in a population with more varied tasks (hospital work). It was suspected that this estimate might be biased if garment workers with musculoskeletal pain were more likely than others to leave employment. METHODS: Retrospective information on date of first onset of symptoms and years employed to date of pain onset, or to survey date (whichever was earlier), was used to calculate age and calendar period-specific rates of onset, conditional on remaining employed until the survey. RESULTS: These rates, and the relative risk for garment work, increased over the 20-year period preceding the year of the survey. The trend was not explained by age or length of employment, or by any known changes in work demands that might have caused a true increase in incidence density. CONCLUSIONS: In the absence of longitudinal cohort data, alternative explanations for these results cannot be excluded. However, with specified assumptions, the most plausible appears to be a healthy worker selection effect acting differentially between high and low exposure groups. This effect would have caused the smallest bias in the prevalence in the year immediately before the survey, and a better estimate of the true relative risk would be approximately five. Where date of onset has been obtained, this method may be used in other cross-sectional studies to estimate and reduce the magnitude of selection bias in a survivor population, if longitudinal data cannot be collected.

Bias↗

Long-term mortality of oil refinery workers. II. Comparison of the experience of active, terminated and retired workers.

In occupational epidemiology a retrospective cohort study normally includes active, terminated, and retired employees and the mortality results may vary considerably if any of the three groups is excluded from the study. From a large refinery cohort of 12,526 white male workers followed between January, 1937 and January, 1978, the mortality experience of three groups (the active, terminated and retired) has been examined; detailed results, along with the merits and problems of studying these groups separately, are presented. The standardized mortality ratios (SMRs) for all causes are 0.68, 1.04 and 0.89 for the active, the terminated and the retired, respectively, and for all cancer, 0.85, 0.98 and 1.05. Significantly decreased SMRs are seen for most of the causes among the active and may be attributed to the "healthy worker effect." Exclusive study of active workers, although it may yield certain useful information, particularly on diseases of the young and those with short latency periods, is primarily a study of the healthy worker effect. Many favorable effects of the active worker will be encountered. The retirees as a whole experienced no significant excess mortality for any causes, although examination of a subgroup, the early retirees, did reveal a significant excess of deaths from diseases of the nervous system and sense organs. The retired may appear to be an ideal group for study because they usually have worked for an extended period of time, they may have experienced long-term occupational exposure and they have lived long enough to develop diseases with long latency periods; however, serious problems arise from studying only the retirees and these are discussed. The terminated group contributed 41% of the person-years, 49% of the total number of individuals and 38% of the deaths and is far too important to be omitted. Contrary to previous reports, the terminated did not demonstrate a significantly adverse mortality experience when compared with the general population, although they did not show the healthy worker effect that was seen among the active.

Adult↗

Confounding by time since hire in internal comparisons of cumulative exposure in occupational cohort studies.

We use a simple, empirical model to describe the healthy worker effect mortality pattern. Under this simple model, internal comparisons of risk with increasing cumulative exposure will tend to be biased away from the null because of the healthy worker effect. We illustrate the potential magnitude of the bias in a simple situation and show that controlling for time since hire, by means of standard epidemiologic methods, eliminates the bias. Time since hire also is a concern of occupational epidemiologists because of the issue of induction time; sufficient time may not have elapsed among recently hired workers for an exposure to manifest its effect on disease occurrence. Provision for an adequate induction period can be addressed, like the concern raised in this paper, by restricting the analysis to workers first employed many years before the start of the follow-up period.

Bias↗

The confounding of occupation and smoking and its consequences.

A strong pattern in smoking behavior can be demonstrated, in which smoking is much more prevalent among those occupational groups (and social strata) that are also more exposed to hazards in the workplace and much less prevalent among those groups less exposed to such hazards. As a consequence, comparing individuals with greater to those with lesser exposure to tobacco also compares groups that differ with respect to occupational exposure to dust, fumes and toxic substances and with respect to occupationally related lifestyle factors. Analyses of the U.S. National Health Interview Survey show that smoking and occupation are substantially confounded among individuals differing by (1) amount of smoking; (2) smoking cessation; (3) types of cigarettes smoked; (4) age of starting to smoke; and (5) exposure to more or less environmental tobacco smoke at home. This confounding between types of work and proximity to tobacco smoke may have masked relationships between type of employment and disease. But it is difficult to disentangle the effects of occupation and of smoking from each other without well planned further studies because (1) of the difficulty of estimating occupational effects and simultaneously adjusting for healthy worker effects, (2) satisfactory techniques for estimating relative effects of intertwined variables make demands on the quality and quantity of data that are not met by presently available data, and (3) there may be deeply rooted social and psychological attitudes toward effects of work versus effects of lifestyles that tend to bias investigative work.

Age Factors↗

Methodological problems of time-related variables in occupational cohort studies.

In studies of long-term health effects of occupational exposures it is important that the time patterns of the study exposure and of the relevant confounders should be taken into account in the analysis. The time-related confounders that have been most frequently considered include age at risk, calendar period, duration of employment, length of follow-up, and employment status (active or retired). These factors are related to the healthy worker effect which is more pronounced among active workers, and declines with length of follow-up. Thus, these time-related factors are potential confounders in occupational cohort studies (and in nested case-control studies). It is therefore advisable to routinely control for length of follow-up and employment status, in addition to the usual confounding factors of age at risk and calendar period. However, it should be stressed that this approach will minimise, but not eliminate, confounding due to the healthy worker effect. In particular, direct control for employment status is inadvisable if this constitutes an intermediate variable in the pathway between exposure and disease, and more complex analytical procedures are necessary in such situations. It is also important that the principle exposure under study should also be analyzed in a time-related manner, taking account of the likely induction and latency periods, and the relative etiological importance of exposure intensity, exposure duration and cumulative exposure. The simplest approach is to analyse the cumulative exposure in a time-related manner, and this may suffice when the aim is merely to consider whether or not there is an effect of exposure. However, once it has been provisionally assumed that an effect exists, attention then shifts to understanding the nature of the effect. In this context, the temporal pattern of exposure and outcome can be considered by examining the effects of exposures in specific time windows while controlling for time-related confounders, and for the effects of exposures in other time windows. A more sophisticated approach is direct fitting of a theoretical model of carcinogenesis, such as the Armitage-Doll or Moolgavkar models. However, it should be emphasized that occupational cohort studies only rarely have sufficient numbers, and data of sufficient quality, to permit meaningful conclusions to be drawn from more sophisticated analyses of this type.

Age Factors↗

[Causes of death of COGEMA active workers, 1980-1995].

BACKGROUND: Populations exposed to risks at work show a deficit in deaths in comparison with the national population, the "healthy worker effect". This effect has been observed among former nuclear workers. The aim of our cross-sectional study was to evaluate the mortality in a metallurgy worker population, and to study the impact of the choice of the reference population on the estimation of the Standardized Mortality Ratio (SMR). METHODS: The studied population was the COGEMA Metallurgy Department workers, aged 25 years to 64, during the period 1980-1995 in two regions of France (North--La Hague; South--Cadarache, Marcoule, Miramas and Pierrelatte). In order to account for geographical variability and the difference in mortality between the working population and the non-working population, we used several reference populations: national population, regional population, "working" national population (farmers not present in COGEMA and non-workers excluded), and "working" regional population. RESULTS: All SMRs were increased when we used a "working" regional reference compared with the national reference population. Among men, eight pathologies presented a significant deficit with a national reference, whereas only two pathologies showed a deficit with the "working" regional reference. CONCLUSION: The use of a reference population close to the study population enabled us to reduce the Healthy Worker Effect among metallurgy workers at COGEMA plants.

Adult↗

Diisocyanate-exposed auto body shop workers: a one-year follow-up.

BACKGROUND: Diisocyanates currently are the most commonly identified cause of occupational asthma in industrialized countries. Auto body shops, a common hexamethylene diisocyanate (HDI) exposure setting, are difficult to study due to their small size and episodic exposures. OBJECTIVES: A 1-year follow-up was undertaken as an adjunct to the cross-sectional SPRAY study (Survey of Painters & Repairers of Auto bodies by Yale) to investigate the effects of HDI on auto body shop workers over time and whether or not the healthy worker effect may exist in this industry. METHODS AND RESULTS: Forty-eight workers from seven shops were re-contacted. Thirty-four subjects who stayed at the same shop and 11 who left their original shop participated. No statistically significant changes in physiology, symptoms, and immunologic responses from baseline to follow-up were noted. However, significant differences between those who left the shops and those who stayed were noted. Those who left were younger, less experienced in the industry, and more likely to have a history of asthma (23 vs. 3%; P < 0.05), bronchial hyper-responsiveness (23 vs. 9%), HDI-specific IgG (64 vs. 29%; P < 0.05), and HDI-specific proliferation (S.I. 2.0 vs. 1.3; P < 0.05). CONCLUSIONS: The differences in workers who stayed at their shop compared to those who left, combined with the low asthma prevalence and high job turnover rate, all suggest that a healthy worker effect may exist in the auto body industry, and may in part account for the low prevalence of asthma noted in SPRAY and other cross-sectional studies of diisocyante workers.

Adult↗

Decline in lung function related to exposure and selection processes among workers in the grain processing and animal feed industry.

OBJECTIVES: To follow up workers in the grain processing and animal feed industry five years after an initial survey, and to monitor exposures to organic dust and endotoxin and changes in prevalence of respiratory symptoms and lung function. METHODS: Outcome measures in the present survey were decline in lung function over five years, rapid annual decline in forced expiratory volume in one second (FEV1) above 90 ml.s-1, and loss to follow up. RESULTS: Among 140 workers included in the longitudinal analysis, annual decline in FEV1 and maximal mid-expiratory flow (MMEF) were significantly related to occupational exposure to dust and endotoxin in the grain processing and animal feed industry. Assuming a cumulative exposure over a working life of 40 years with an exposure of 5 mg.m-3, the estimated effect on the FEV1 would be a decline of 157 ml.s-1 (95% CI 13 to 300)--that is, about 4% of the group mean FEV1 and 473 ml.s-1 (95% CI 127 to 800) of the MMEF (about 12%). Workers with a dust exposure > 4 mg.m-3 or endotoxin concentrations > 20 ng.m-3 at the 1986-8 survey had significantly higher risk of rapid decline in FEV1 (odds ratio (OR) 3.3, 95% CI 1.02 to 10.3). The relations between occupational exposure and decline in lung function in this study occurred, despite the selection through the healthy worker effect that occurred as well. Increasing working years was related to decreasing annual decline in FEV1 and fewer people with rapid decline in FEV1 (OR 0.04, 95% CI 0 to 0.61 for over 20 v < 5 working years in the grain processing and animal feed industry). The presence of respiratory symptoms at baseline was a strong predictor of subsequent loss to follow up. Baseline lung function was not found to be predictive of subsequent loss to follow up. However, among workers lost to follow up the number of working years was more strongly negatively related to baseline lung function than among the workers who were studied longitudinally. CONCLUSIONS: The existence of the healthy worker effect implies that an exposure-response relation in the grain processing and animal feed industry may well be underestimated. This should be taken into account when health based recommended limit values are to be developed.

Adult↗